bluuebunny/crossref_metadata_2025 huggingface dataset:
Dating “Sweet Desire”
Authors: Wise Dennis Wilson
Published: November 2023

C. S. Lewis and J. R. R. Tolkien are two key figures in the Modern Alliterative Revival, and each sought to revive Old English poetics with close to absolute metrical fidelity. While scholarship on Tolkien’s alliterative verse has seen an uptick in recent years, though, Lewis remains the odd poet out. Nominally, this article attempts to assign a composition date for Lewis’s poem “Sweet Desire.” My dating to early 1930 associates this text with Lewis’s famous conversion to theism. More broadly, this article tracks one revivalist’s painstaking adaptation of the alliterative meter into Modern English, outlining the technical challenges faced by Lewis and which other contemporary revivalists must overcome as well.
Bridging condensins mediate compaction of mitotic chromosomes
Authors: Forte Giada , Boteva Lora , Conforto Filippo , Gilbert Nick , Cook Peter R. , Marenduzzo Davide
Published: November 2023

Eukaryotic chromosomes compact during mitosis into elongated cylinders—and not the spherical globules expected of self-attracting long flexible polymers. This process is mainly driven by condensin-like proteins. Here, we present Brownian-dynamic simulations involving two types of such proteins with different activities. One, which we refer to as looping condensins, anchors long-lived chromatin loops to create bottlebrush structures. The second, referred to as bridging condensins, forms multivalent bridges between distant parts of these loops. We show that binding of bridging condensins leads to the formation of shorter and stiffer mitotic-like cylinders without requiring any additional energy input. These cylinders have several features matching experimental observations. For instance, the axial condensin backbone breaks up into clusters as found by microscopy, and cylinder elasticity qualitatively matches that seen in chromosome pulling experiments. Additionally, simulating global condensin depletion or local faulty condensin loading gives phenotypes seen experimentally and points to a mechanistic basis for the structure of common fragile sites in mitotic chromosomes.
Women in STEM becoming independent: Science thrives on diverse perspectives
Authors: Van Emmenis Lucie
Published: November 2023

In this Viewpoint, we hear from a cross section of women, across multiple research fields, discussing their science and the process of setting up a lab as an independent researcher. As well as being able to celebrate the positives of becoming an independent researcher, we would also like to use this platform to discuss the unique challenges they face as women scientists in their respective scientific environments.
Techno-economic analysis of a hybrid renewable energy system integrated with productive activities in an underdeveloped rural region of eastern Indonesia
Authors: Shafira Alya Nurul , Petrana Subhan , Muthia Rahma , Purwanto Widodo Wahyu
Published: November 2023

The Southwest Maluku region in eastern Indonesia is considered a frontier, outermost and underdeveloped region. Its inhabitants live on isolated islands, including the residents of Mahaleta Village, where only 9.4% of the community have limited access to electricity. This study aimed to design an economically feasible hybrid renewable energy (RE) system based on solar and wind energy to integrate with the productive activities of the village. The study developed conceptual schemes to meet the demand for electricity from the residential, community, commercial and productive sectors of the village. The analysis was performed using a techno-economic approach. The hybrid system was designed using the HOMER Pro optimization function, and cold-storage and dryer systems were designed to support related productive activities. The optimized design of the hybrid RE system comprised 271.62 kW of solar photovoltaics, 80 kW of wind turbines and a 1-MWh lead–acid battery. We found that the hybrid RE system would only be economically feasible with a full-grant incentive and an electricity tariff of $0.0808/kWh. However, the productive activity schemes were all economically feasible, with a cold-storage cost of $0.035/kg and a drying cost of $0.082/kg. Integrating the hybrid RE system with productive activities can improve the economic feasibility of the energy system and create more jobs as well as increase income for the local community.
Genetic analysis of a genus of plant mimics (Alseuosmia A.Cunn; Alseuosmiaceae) reveals incongruence between morphology and phylogeny and possible mimetic polymorphism
Authors: Shepherd Lara D , Townsend Andrew , de Lange Peter J , Perrie Leon R
Published: November 2023

Alseuosmia (Alseuosmiaceae) is an endemic New Zealand genus of small trees and shrubs, which is unusual in that some taxa appear to morphologically mimic unrelated species. The taxonomy of the group has long been debated, with the extreme morphological diversity in A. banksii causing much of the confusion. Here we use ddRADseq to examine the genetic relationships between species of the genus, with a particular focus on the morphological forms of A. banksii. Our analyses revealed that for species in the northern part of the distribution, genetic relationships largely matched geography rather than species boundaries based on morphology, and that hybridization between morphs appears to be common. A diversity of morphologies is present within these northern Alseuosmia, including multiple forms that appear to mimic unrelated genera, and these may constitute a single gene pool. Further south, two species (A. turneri and A. pusilla) were genetically distinct in sympatry. We suggest maintaining the current taxonomy until further research can be undertaken.
Mitochondrial aminoacyl-tRNA synthetases trigger unique compensatory mechanisms in neurons
Authors: Podmanicky Oliver , Gao Fei , Munro Benjamin , Jennings Matthew J , Boczonadi Veronika , Hathazi Denisa , Mueller Juliane S , Horvath Rita
Published: November 2023

Mitochondrial aminoacyl-tRNA synthetase (mt-ARS) mutations cause severe, progressive, and often lethal diseases with highly heterogeneous and tissue-specific clinical manifestations. This study investigates the molecular mechanisms triggered by three different mt-ARS defects caused by biallelic mutations in AARS2, EARS2, and RARS2, using an in vitro model of human neuronal cells. We report distinct molecular mechanisms of mitochondrial dysfunction among the mt-ARS defects studied. Our findings highlight the ability of proliferating neuronal progenitor cells (iNPCs) to compensate for mitochondrial translation defects and maintain balanced levels of oxidative phosphorylation (OXPHOS) components, which becomes more challenging in mature neurons. Mutant iNPCs exhibit unique compensatory mechanisms, involving specific branches of the integrated stress response, which may be gene-specific or related to the severity of the mitochondrial translation defect. RNA sequencing revealed distinct transcriptomic profiles showing dysregulation of neuronal differentiation and protein translation. This study provides valuable insights into the tissue-specific compensatory mechanisms potentially underlying the phenotypes of patients with mt-ARS defects. Our novel in vitro model may more accurately represent the neurological presentation of patients and offer an improved platform for future investigations and therapeutic development.
Epigenomic profiling of the infrapatellar fat pad in osteoarthritis
Authors: Kreitmaier Peter , Park Young-Chan , Swift Diane , Gilly Arthur , Wilkinson J Mark , Zeggini Eleftheria
Published: November 2023

Osteoarthritis is a prevalent, complex disease of the joints, and affects multiple intra-articular tissues. Here, we have examined genome-wide DNA methylation profiles of primary infrapatellar fat pad and matched blood samples from 70 osteoarthritis patients undergoing total knee replacement surgery. Comparing the DNA methylation profiles between these tissues reveal widespread epigenetic differences. We produce the first genome-wide methylation quantitative trait locus (mQTL) map of fat pad, and make the resource available to the wider community. Using two-sample Mendelian randomization and colocalization analyses, we resolve osteoarthritis GWAS signals and provide insights into the molecular mechanisms underpinning disease aetiopathology. Our findings provide the first view of the epigenetic landscape of infrapatellar fat pad primary tissue in osteoarthritis.
Effects of automation on the gender pay gap: the case of Estonia
Authors: Pavlenkova Ilona , Alfieri Luca , Masso Jaan
Published: November 2023

This paper investigates how investments in automation affect the gender pay gap. The evidence of the effects of automation on the labor market is growing; however, little is known about the implications of automation for the gender pay gap. The data used in this paper are from a matched employer–employee dataset incorporating detailed information on firms, their imports, and employee–level data for Estonian manufacturing and service employers for the period of 2006–2018. Through the use of the imports of automation goods as a proxy for the introduction of automation at the firm level, this paper estimates the effect of automation using simple Mincerian wage equations. The causality of the effect is further validated using propensity score matching (PSM). We find that introducing automation enlarges the gender pay gap, and PSM confirms that this also has a higher causal effect on the wages of male employees than female employees. The results imply that a higher representation of women in higher-paid positions does not guarantee a reduction in the gender pay gap in the presence of automation, and appropriate measures in education and retraining are needed to tackle the effect of automation on gender inequality.
The impact of second transurethral resection on survival outcomes in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette–Guérin therapy
Authors: Kikuchi Hiroshi , Abe Takashige , Miyake Makito , Miyata Haruka , Matsumoto Ryuji , Osawa Takahiro , Nishimura Nobutaka , Fujimoto Kiyohide , Inokuchi Junichi , Yoneyama Takahiro , Tomida Ryotaro , Numakura Kazuyuki , Matsushita Yuto , Matsumoto Kazumasa , Sato Takuma , Taoka Rikiya , Kobayashi Takashi , Kojima Takahiro , Matsui Yoshiyuki , Nishiyama Naotaka , Kitamura Hiroshi , Nishiyama Hiroyuki , Shinohara Nobuo
Published: November 2023

Objective

Several guidelines recommended that second transurethral resection should be performed in patients with diagnosis of high-risk non-muscle-invasive bladder cancer. However, therapeutic benefits of second transurethral resection before bacillus Calmette–Guérin intravesical instillation were conflicting amongst previous studies. We investigated the prognostic impact of second transurethral resection before bacillus Calmette–Guérin instillation in high-risk non-muscle-invasive bladder cancer patients.

Methods

This retrospective study included 3104 non-muscle-invasive bladder cancer patients who received bacillus Calmette–Guérin instillations between 2000 and 2019 at 31 collaborative institutions. Univariate and multivariate Cox proportional hazards models were used to assess the risk factors of intravesical recurrence, disease progression, cancer-specific mortality and overall mortality.

Results

In the entire population, patients undergoing second transurethral resection (33%, 1026/3104) had a lower risk of intravesical recurrence on univariate analysis (hazard ratio 0.85, 95% confidence interval 0.73–0.98, P = 0.027), although it did not remain significant on multivariate analysis (hazard ratio 0.90, 95% confidence interval 0.76–1.07, P = 0.24). Subgroup analysis revealed that, in pT1 patients (n = 1487), second transurethral resection was significantly correlated with a lower risk of intravesical recurrence on multivariate analysis (hazard ratio 0.80, 95% confidence interval 0.64–1.00, P = 0.048), but lower risks of disease progression (hazard ratio 0.75, 95% confidence interval 0.56–1.00, P = 0.049), cancer-specific mortality (hazard ratio 0.54, 95% confidence interval 0.35–0.85, P = 0.007) and overall mortality (hazard ratio 0.73, 95% confidence interval 0.55–0.97, P = 0.027) on univariate analysis.

Conclusions

Second transurethral resection confers accurate pathological staging and could be used to safely select good candidates for intravesical bacillus Calmette–Guérin instillation. We further confirm that second transurethral resection could confer an oncological benefit in pT1 bladder cancer patients treated by bacillus Calmette–Guérin instillation, and so strongly recommend second transurethral resection in this patient population.
Plant age-dependent dynamics of annatto pigment (bixin) biosynthesis in Bixa orellana
Authors: Machado Kleiton Lima de Godoy , Faria Daniele Vidal , Duarte Marcos Bruno Silva , Silva Lázara Aline Simões , de Oliveira Tadeu dos Reis , Falcão Thais Castilho Arruda , Batista Diego Silva , Costa Marcio Gilberto Cardoso , Santa-Catarina Claudete , Silveira Vanildo , Romanel Elisson , Otoni Wagner Campos , Nogueira Fabio Tebaldi Silveira
Published: November 2023

Age affects the production of secondary metabolites, but how developmental cues regulate secondary metabolism remains poorly understood. The achiote tree (Bixa orellana L.) is a source of bixin, an apocarotenoid used in diverse industries worldwide. Understanding how age-dependent mechanisms control bixin biosynthesis is of great interest for plant biology and for economic reasons. Here we overexpressed miRNA156 (miR156) in B. orellana to comprehensively study the effects of the miR156–SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) module on age-dependent bixin biosynthesis in leaves. Overexpression of miR156 in annatto plants (miR156ox) reduced BoSPL transcript levels, impacted leaf ontogeny, lessened bixin production, and increased abscisic acid levels. Modulation of expression of BoCCD4-4 and BoCCD1, key genes in carotenoid biosynthesis, was associated with diverting the carbon flux from bixin to abscisic acid in miR156ox leaves. Proteomic analyses revealed an overall low accumulation of most secondary metabolite-related enzymes in miR156ox leaves, suggesting that miR156-targeted BoSPLs may be required to activate several secondary metabolic pathways. Our findings suggest that the conserved BomiR156–BoSPL module is deployed to regulate leaf dynamics of bixin biosynthesis, and may create novel opportunities to fine-tune bixin output in B. orellana breeding programs.
An essential role for mannan degradation in both cell growth and secondary cell wall formation
Authors: Zhang Rui , Li Bo , Zhao Yunjun , Zhu Yingying , Li Laigeng
Published: November 2023

Coordination of secondary cell wall deposition and cell expansion during plant growth is required for cell development, particularly in vascular tissues. Yet the fundamental coordination process has received little attention. We observed that the Arabidopsis endo-1,4-mannanase gene, AtMAN6, is involved in the formation of cell walls in vascular tissues. In the inflorescence stem, the man6 mutant had smaller vessel cells with thicker secondary cell walls and shorter fiber cells. Elongation growth was reduced in the root, and secondary cell wall deposition in vessel cells occurred early. Overexpression of AtMAN6 resulted in the inverse phenotypes of the man6 mutant. AtMAN6 was discovered on the plasma membrane and was specifically expressed in vessel cells during its early development. The AtMAN6 protein degraded galactoglucomannan to produce oligosaccharides, which caused secondary cell wall deposition in vessel and fiber cells to be suppressed. Transcriptome analysis revealed that the expression of genes involved in the regulation of secondary cell wall synthesis was changed in both man6 mutant and AtMAN6 overexpression plants. AtMAN6’s C-terminal cysteine repeat motif (CCRM) was found to facilitate homodimerization and is required for its activity. According to the findings, the oligosaccharides produced by AtMAN6 hydrolysis may act as a signal to mediate this coordination between cell growth and secondary cell wall deposition.
Observation of a propagating slow magnetoacoustic wave in a coronal plasma fan with SDO/AIA and SolO/EUI
Authors: Meadowcroft Rebecca L , Zhong Sihui , Kolotkov Dmitrii Y , Nakariakov Valery M
Published: November 2023

Simultaneous observations of a propagating disturbance of EUV intensity, with SDO/AIA at 171 Å and SolO/EUI-HRIEUV at 174 Å, are investigated. The disturbance moves outwards along a plasma fan structure in active region AR 12941 on February 7th 2022, at 12:45–14:15 UT. The spacecraft line-of-sight separation is 19°. The variation of the EUV intensity resembles an almost harmonic wave with an oscillation period of $2.7^{+0.1}_{-0.2}$ and $2.6^{+0.1}_{-0.1}$ min for AIA and HRIEUV, respectively. Over 30 oscillation cycles are detected. The wave originated at the footpoint of the fan, anchored in a sunspot. The projected phase speeds are 60.5 ± 5.2 and 74.4 ± 6.2 km s−1 in the AIA and HRIEUV data, respectively, determined by the cross-correlation technique. The observed parameters of the propagating EUV disturbance suggest its interpretation as a slow magnetoacoustic wave. Observations with AIA show that the wave decays with height, with a calculated e-folding length of $6.9^{+1.3}_{-0.8}$ Mm. In contrast, in the HRIEUV data, the propagating EUV disturbance is also seen much higher, with the e-folding length of $12.8^{+1.1}_{-1.7}$ Mm. This observation demonstrates, for the first time, that the apparent spatial damping of propagating slow waves depends on the observational instrument. Moreover, our work shows that the study of slow waves can be advanced with the use of HRIEUV, and multiple instruments with non-parallel lines of sight.
Hierarchical Bayesian inference of globular cluster properties
Authors: Wen Robin Y , Speagle Joshua S , Webb Jeremy J , Eadie Gwendolyn M
Published: November 2023

We present a hierarchical Bayesian inference approach to estimating the structural properties and the phase-space centre of a globular cluster (GC) given the spatial and kinematic information of its stars based on lowered isothermal cluster models. As a first step towards more realistic modelling of GCs, we built a differentiable, accurate emulator of the lowered isothermal distribution function using interpolation. The reliable gradient information provided by the emulator allows the use of Hamiltonian Monte Carlo methods to sample large Bayesian models with hundreds of parameters, thereby enabling inference on hierarchical models. We explore the use of hierarchical Bayesian modelling to address several issues encountered in observations of GC including an unknown GC centre, incomplete data, and measurement errors. Our approach not only avoids the common technique of radial binning but also incorporates the aforementioned uncertainties in a robust and statistically consistent way. Through demonstrating the reliability of our hierarchical Bayesian model on simulations, our work lays out the foundation for more realistic and complex modelling of real GC data.
The cluster mass function and the σ8 tension
Authors: Papageorgiou A , Plionis M , Basilakos S , Abdullah M H
Published: November 2023

We use a large set of halo mass function (HMF) models in order to investigate their ability to represent the observational cluster mass function (CMF), derived from the $\tt {GalWCat19}$ cluster catalogue, within the Lambda cold dark matter (ΛCDM) cosmology. We apply the χ2 minimization procedure to constrain the free parameters of the models, namely Ωm and σ8. We find that all HMF models fit well the observational CMF, while the Bocquet et al. model provides the best fit, with the lowest χ2 value. Utilizing the index of inconsistency (IOI) measure, we further test the possible inconsistency of the models with respect to a variety of Planck 2018 ΛCDM cosmologies, resulting from the combination of different probes (CMB–BAO or CMB–DES). We find that the HMF models that fitted well the observed CMF provide consistent cosmological parameters with those of the Planck CMB analysis, except for the Press and Schechter, Yahagi et al., and Despali et al. models that return large IOI values. The inverse $\chi _{\rm min}^2$-weighted average values of Ωm and σ8, overall 23 theoretical HMF models are ${\bar{\Omega }_{m,0}}=0.313\pm 0.022$ and ${\bar{\sigma }_8}=0.798\pm 0.040$, which are clearly consistent with the results of Planck–CMB, providing S8 = σ8(Ωm/0.3)1/2 = 0.815 ± 0.05. Within the ΛCDM paradigm and independently of the selected HMF model in the analysis, we find that the current CMF shows no σ8 tension with the corresponding Planck–CMB results.
Tidal dissipation in satellites prevents Hill sphere escape
Authors: Kisare A M , Fabrycky D C
Published: November 2023

The transit method is a promising means of detecting exomoons, but few candidates have been identified. For planets close to their stars, the dynamical interaction between a satellite’s orbit and the star must be important in their evolution. Satellites beyond synchronous orbit spiral out due to the tide raised on their planet, and it has been assumed that they would likely escape the Hill sphere. Here we follow the evolution with a three-body code that accounts for tidal dissipation within both the planet and the satellite. We show that tidal dissipation in satellites often keeps them bound to their planet, making exomoons more observable than previously thought. The probability of escape depends on the ratio of tidal quality factors of the planet and satellite; when this ratio exceeds 0.5, escape is usually avoided. Instead, the satellite moves to an equilibrium in which the spin angular momentum of the planet is not transferred into the orbit of the satellite, but is transferred into the orbit of the planet itself. While the planet continues spinning faster than the satellite orbits, the satellite maintains a semi-major axis of approximately 0.41 Hill radii. These states are accompanied with modest satellite eccentricity near 0.1 and are found to be stable over long time-scales.
First asteroseismic analysis of the globular cluster M80: multiple populations and stellar mass-loss
Authors: Howell Madeline , Campbell Simon W , Stello Dennis , De Silva Gayandhi M
Published: November 2023

Asteroseismology provides a new avenue for accurately measuring the masses of evolved globular cluster (GC) stars. We present the first detections of solar-like oscillations in 47 red giant branch (RGB) and early asymptotic giant branch (EAGB) stars in the metal-poor GC M80; only the second with measured seismic masses. We investigate two areas of stellar evolution and GC science: multiple populations and stellar mass-loss. We detect a distinct bimodality in the EAGB mass distribution. We suggest that this could be due to sub-population membership. If confirmed in future work with spectroscopy, it would be the first direct measurement of a mass difference between sub-populations. A mass difference was not detected between the sub-populations in our RGB sample. We instead measured an average RGB mass of $0.782\pm 0.009~\mathrm{M}_{\odot }$, which we interpret as the average of the sub-populations. Differing mass-loss rates on the RGB have been proposed as the second parameter that could explain the horizontal branch morphology variations between GCs. We calculated an integrated RGB mass-loss separately for each sub-population: $0.12\pm 0.02~\mathrm{M}_{\odot }$ (SP1) and $0.25\pm 0.02~\mathrm{M}_{\odot }$ (SP2). Thus, SP2 stars appear to have enhanced mass-loss on the RGB. Mass-loss is thought to scale with metallicity, which we confirm by comparing our results to a higher metallicity GC, M4. Finally, our study shows the robustness of the Δν-independent mass scaling relation in the low-metallicity (and low surface gravity) regime.
Increase nurse faculty salaries to reduce the nursing shortage
Authors: Kroning Maureen , Northrup Angela
Published: November 2023

Recruiting and retaining qualified nurse educators is vital to addressing the nursing shortage and ensuring the health and well-being of current nurses in our communities. However, low faculty salaries remain a major barrier to recruiting and retaining qualified nurse educators.
Age-Friendly Health Systems
Authors: Raparla Amor , Thorngthip Sutthinee , Pino Lilia , Hughes Robin , Pohnert Anne M. , Dolansky Mary A.
Published: November 2023

This article discusses the Age-Friendly Health Systems (AFHS) initiative, which aims to provide safe and effective care for older adults by focusing on the 4Ms framework: What Matters, Medication, Mentation, and Mobility. This article also outlines strategies for educating nurses on incorporating the AFHS initiative into their routine care and the potential impact on nursing care for older adults.
Leiomyoma Fistulization After Uterine Artery Embolization
Authors: Yu Lulu , Lee Ziho , Brown Oluwateniola , Yang Linda C.
Published: November 2023

BACKGROUND:

Uterine artery embolization (UAE) has been used to treat symptomatic uterine leiomyomas since 1995. This case report describes a rare complication of UAE, with delayed recognition, ultimately requiring definitive hysterectomy.

CASE:

A 53-year-old women with symptomatic leiomyomas underwent imaging demonstrating an enlarged (16.9×11.3×11.5 cm) uterus with multiple leiomyomas. She underwent UAE and, over the subsequent 3 months, and had five emergency department visits for abdominal pain and dysuria. Pelvic magnetic resonance imaging (MRI) 4 months postprocedure showed nodular mural enhancement of the right anterior bladder dome, and cystoscopy demonstrated irregular tissue on the right dome of the bladder. The patient ultimately underwent total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, partial cystectomy with reconstruction, and omental flap for bladder necrosis and leiomyoma fistulization.

CONCLUSION:

Bladder necrosis and leiomyoma fistulization are rare complications of UAE that can present with pelvic pain, hematuria, and recurrent bladder stones. Computed tomography and MRI can be useful tools in evaluating for complications, but clinicians should have a low threshold to use cystoscopy to directly visualize potential abnormalities identified on imaging. Patients with complex cases with suspected post-UAE complications warrant referral to tertiary care centers for a multidisciplinary approach.
Incidence of Focal Osteolysis in a Titanium Limb-Lengthening Device: A Comparison to a Stainless-Steel Model
Authors: Sax Oliver C. , Hlukha Larysa P. , Kowalewski Kyle A. , Bains Sandeep S. , Dubin Jeremy A. , Herzenberg John E. , Assayag Michael J. , McClure Philip K.
Published: November 2023

Objectives:

To evaluate 1 manufacturer's titanium intramedullary lengthening nail (ILN) for radiographic evidence of adverse tissue reactions similar to those in their stainless-steel ILN that was recalled in 2021, with specific outcomes of (1) incidence of periosteal reaction and osteolysis and (2) adverse tissue reaction-related device failures.

Design:

Radiographic review of consecutive patients with ≥1-year clinical follow-up who received 1 manufacturer's ILNs implanted in the femur and/or tibia from February 2012 to July 2021.

Setting:

Single tertiary-care center.

Patients/Participants:

Two hundred twenty-six limbs with titanium ILNs and 57 limbs with stainless-steel ILNs.

Intervention:

Precice titanium ILN (NuVasive Specialized Orthopedics, San Diego, CA) and Stryde stainless-steel ILN (NuVasive Specialized Orthopedics).

Main Outcome Measurements:

Radiographic outcome data and complications.

Results:

Of 226 limbs with titanium ILNs, 160 (70.8%) had periosteal reaction, and 2 (0.9%) had osteolysis. Periosteal reaction and osteolysis rates in stainless-steel ILNs (57 limbs) were 39% and 26%, respectively. No adverse tissue reaction-related device failures were noted with titanium. Several other complications presented, notably hip and/or knee tissue contracture (141), consolidation problems (8), and needing peroneal nerve decompression (14).

Conclusions:

Osteolysis incidence was substantially less among the titanium population, supporting the claim that observed osteolysis in the stainless-steel cohort was attributed to its construct. On average, periosteal reaction was radiographically appreciated later in patients with titanium than stainless steel. Further study is needed to confirm this finding.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Vessel Density Features of Optical Coherence Tomography Angiography for Classification of Glaucoma Using Machine Learning
Authors: Jalili Jalil , Nadimi Mohadeseh , Jafari Behzad , Esfandiari Amirreza , Sadeghi Reza , Ghahari Parichehr , Sajedi Marziyeh , Safizade Mona , Aghsaei Fard Masoud
Published: November 2023

Précis:

Machine learning (ML) based on the optical coherence tomography angiography vessel density features with different thresholds using a support vector machine (SVM) model provides excellent performance for glaucoma detection.

Background:

To assess the classification performance of ML based on the 4 vessel density features of peripapillary optical coherence tomography angiography for glaucoma detection.

Methods:

Images from 119 eyes of 119 glaucoma patients and 76 eyes of 76 healthy individuals were included. Four vessel density features of optical coherence tomography angiography images were developed using a threshold-based segmentation method and were integrated into 3 models of machine learning classifiers. Images were divided into 70% training set and 30% test set. Classification performances of SVM, random forest, and Gaussian Naive Bayes models were evaluated with the area under the receiver operating characteristic curve (AUC) and accuracy.

Results:

Glaucoma eyes had lower vessel densities at different thresholds. For differentiating glaucoma eyes, the best results were achieved with 70% and 100% thresholds, in which SVM classifier discriminated glaucoma from healthy eyes with an AUC of 1 and accuracy of 1. After SVM, the random forest classifier with 100% thresholds showed an AUC of 0.993 and an accuracy of 0.994. Furthermore, the AUC of our ML performance (SVM) was 0.96 in a subgroup analysis of mild and moderate glaucoma eyes.

Conclusions:

ML based on the combined peripapillary vessel density features of total vessels and capillaries in the whole image and ring image could provide excellent performance for glaucoma detection.
Real-world outcomes in spinal cord stimulation: predictors of reported effect and explantation using a comprehensive registry-based approach
Authors: Kirketeig Terje , Söreskog Emma , Jacobson Trolle , Karlsten Rolf , Zethraeus Niklas , Borgström Fredrik
Published: November 2023

Introduction:

Despite advancements in implanted hardware and development of novel stimulation paradigms in Spinal Cord Stimulation (SCS), real world evidence suggests a large variation in patient reported outcomes and a proportion of patients are later explanted due to loss of analgesia. Possible predictors for outcome have been explored in smaller short-term evaluations, but few clinically applicable robust measures for long term outcome have emerged.

Methods:

We performed a comprehensive retrospective study based on an assembled patient-level aggregated database from multiple local and national registries in Sweden. Variables associated with risk of explantation (due to insufficient analgesia) and analgesic effect was analyzed using a Cox regression analysis and an ordered logit regression model, respectively.

Results:

We found the accumulated risk of explantation due to loss of analgesia to be 10% and 21% at two and ten years follow up, respectively. The use of 10 kHz spinal cord stimulation (compared with Tonic waveform; p = 0.003), and being 60 years or older (reference 18-40 years; p = 0.003) were associated with an increased risk of explantation.

At a mean follow up at 1 year, 48% of patients reported a pain intensity reduction from baseline of at least 30%. Secondary (p = 0.030) and post-secondary (p = 0.001) education (compared with primary education) was associated with an increased probability of successful patient reported outcomes.

Conclusion:

This study suggests that a higher educational level and being employed are associated with successful treatment outcome in patients with chronic pain treated with SCS in Sweden.
68Ga-FAPI and 18F-FDG Uptake in a Patient With Esophageal Candida Infection
Authors: Chen Xi , Liu Mengna , Yang Liping , Shu Qiaoqiao , Cai Liang
Published: November 2023

A 67-year-old woman presented with dysphagia for 2 months. Enhanced chest CT suggested thickening of the esophageal wall, which was suspected to be a malignancy. The patient then underwent 18F-FDG and 68Ga-FAPI PET/CT. Increased uptake was observed in both tracers in the thickened esophageal wall. However, biopsy demonstrated candida infection of esophagus. After treatment, the symptoms of the patient were relieved.
Atypical Layering of FDG in Pleural Effusion
Authors: Han Eun Ji , Yoon Hyukjin , Choi Woo Hee
Published: November 2023

Radiopharmaceuticals can accumulate in malignant or nonmalignant pleural effusion on γ and PET imaging, and effusion shows a pattern of diffusely or focally increased activity. Herein, we report atypical layering of FDG in pleural effusion on PET/CT of 3 patients with metastatic gynecological cancer.
Successful Reduction of Unilateral Zygoma Fracture Following Bilateral Malar Reduction Surgery
Authors: Park Ji Hae , Park Yun Joo , Park Tae Hwan
Published: November 2023

Malar reduction surgery can increase its susceptibility to fractures in case of trauma. Patients who had malar reduction surgery and sustained a zygoma fracture pose unique challenges for treatment and management. This is a case of a 28-year-old female patient who presented with a unilateral zygoma fracture following bilateral malar reduction and augmentation rhinoplasty 6 years ago. Physical examination revealed a clicking sound when opening the mouth at the right zygomatic buttress and a depressed preauricular area, suggesting arch fracture. Computed tomography imaging demonstrated a loosened screw at the right zygomatic buttress and a depressed arch fracture. She wanted to remove all plates and treat her right fractured zygoma with absorbable materials. Through the bilateral intraoral incisions, the authors removed the plates and screws and reduced the depression with the Langenbeck elevator through the same right intraoral incision without fixation. The reduction was well-maintained without complications based on postoperative plain x-rays 1 month after surgery. She reported that the pain was mostly gone and that she did not hear any abnormal sounds when opening her mouth after the surgery. In this case, if the zygomaticomaxillary buttress is minimally displaced, but the zygomatic arch fracture is significantly depressed, the authors believe that fracture reduction with only an intraoral incision would be enough to achieve an optimal outcome. If the plates and screws used in the previous malar reduction are not well maintained, it may be necessary to remove them.
A Temporary Intraoperative Fixation Method for the Absorbable Plates Fixation of Condylar Fracture by Retromandibular Transparotid Approach
Authors: Tao Yan-Kai , Zhao Yang , Li Zhi
Published: November 2023

The authors describe a temporary intraoperative fixation method for the absorbable plates’ fixation of subcondylar fracture by retromandibular transparotid approach. First, the fracture was temporarily fixed with a 4-hole titanium microplate across the fracture line in the center of the lateral surface of the condyle to maintain the reduction of the fracture. Then, two 4-hole absorbable mini-plates were fixed on the posterior and anterior border of the condylar neck. Finally, the 4-hole titanium microplate and screws were removed before the wound closure. In the absorbable plates’ fixation of subcondylar fracture by transparotid approach, the method of temporary intraoperative fixation using a 4-hole titanium microplate offsets the limited exposure of the operative field, smooths the operation, and offers the reliability and validity of the absorbable plates’ fixation.
Consolidating evidence on the role of insulin resistance in major depressive disorder
Authors: Krupa Anna Julia , Dudek Dominika , Siwek Marcin
Published: November 2023

Purpose of review

The circular interactions between type 2 diabetes (TMD2) and major depressive disorder (MDD) are well documented but the understanding of their mechanisms has only recently gained more clarity. Latest research indicates, that the association between TMD2 and MDD is largely mediated by insulin resistance (IR).

Recent findings

A metabolic subtype of MDD can be distinguished from other MDD subpopulations, that is characterized by predominantly atypical clinical presentation, IR and different responsiveness to antidepressant interventions. IR is a predictor of nonresponse to some antidepressants. The IR seems to be a state-marker of clinical or subclinical depression and the relationship between IR and MDD varies between sexes and ethnicities. Insulin has a direct impact on the monoaminergic systems known to underlie MDD symptoms: serotoninergic and dopaminergic, which are dysregulated in IR subjects. Several trials assessed the efficacy of insulin-sensitizing drugs in MDD with mixed results for metformin and more consistent evidence for pioglitazone and lifestyle intervention/physical activity.

Recently published data suggest a significant role of IR in the clinical presentation, pathophysiology and treatment response in MDD. Further research of IR in MDD and integration of existing data into clinical practice are needed.
Bovine papular stomatitis virus as a vaccine vector for cattle
Authors: Delhon Gustavo , Khatiwada Sushil , Doub David , Harris Seth , Chaulagain Sabal , El-Gaffary Mostafa , Rock Daniel L.
Published: November 2023

Virus vectored vaccines are not available commercially for cattle even though compelling potential applications exist. Bovine papular stomatitis virus (BPSV), a highly prevalent parapoxvirus, causes self-limited oral lesions in cattle. Ability of virus to accommodate large amounts of foreign DNA, induce low level of antiviral immunity, and circulate and likely persist in cattle populations, make BPSV an attractive candidate viral vector. Here, recombinant BPSV were constructed expressing either Bovine herpesvirus 1 (BoHV-1) glycoprotein gD (BPSVgD), or gD and gB (BPSVgD/gB). Immunization of BPSV serologically-positive calves with BPSVgD or BPSVgD/gB induced BoHV-1 neutralization antibodies and provided protection for three of four animals following a high dose BoHV-1 challenge at day 70 pi. Results indicate BPSV suitability as a candidate virus vector for cattle vaccines.
IMGT/RobustpMHC: Robust Training for class-I MHC Peptide Binding Prediction
Authors: Kushwaha Anjana , Duroux Patrice , Giudicelli Véronique , Todorov Konstantin , Kossida Sofia
Published: November 2023

The accurate prediction of peptide-MHC class I binding probabilities is a critical endeavor in immunoinformatics, with broad implications for vaccine development and immunotherapies. While recent deep neural network based approaches have showcased promise in peptide-MHC prediction, they have two shortcomings: (i) they rely on hand-crafted pseudo-sequence extraction, (ii) they do not generalise well to different datasets, which limits the practicality of these approaches. In this paper, we present PerceiverpMHC that is able to learn accurate representations on full-sequences by leveraging efficient transformer based architectures. Additionally, we propose IMGT/RobustpMHC that harnesses the potential of unlabeled data in improving the robustness of peptide-MHC binding predictions through a self-supervised learning strategy. We extensively evaluate RobustpMHC on 8 different datasets and showcase the improvements over the state-of-the-art approaches. Finally, we compile CrystalIMGT, a crystallography verified dataset that presents a challenge to existing approaches due to significantly different peptide-MHC distributions.
Evolutionary arms race between SARS-CoV-2 and interferon signaling via dynamic interaction with autophagy
Authors: Lee Jae Seung , Dittmar Mark , Miller Jesse , Li Minghua , Ayyanathan Kasirajan , Ferretti Max , Hulahan Jesse , Whig Kanupriya , Etwebi Zienab , Griesman Trevor , Schultz David C. , Cherry Sara
Published: November 2023

SARS-CoV-2 emerged, and is evolving to efficiently infect humans worldwide. SARS-CoV-2 evades early innate recognition, interferon signaling activated only in bystander cells. This balance of innate activation and viral evasion has important consequences, but the pathways involved are incompletely understood. Here we find that autophagy genes regulate innate immune signaling, impacting the basal set point of interferons, and thus permissivity to infection. Mechanistically, autophagy genes negatively regulate MAVS, and this low basal level of MAVS is efficiently antagonized by SARS-CoV-2 ORF9b, blocking interferon activation in infected cells. However, upon loss of autophagy increased MAVS overcomes ORF9b-mediated antagonism suppressing infection. This has led to the evolution of SARS-CoV-2 variants to express higher levels of ORF9b, allowing SARS-CoV-2 to replicate under conditions of increased MAVS signaling. Altogether, we find a critical role of autophagy in the regulation of innate immunity and uncover an evolutionary trajectory of SARS-CoV-2 ORF9b to overcome host defenses.
The Lactate Receptor GPR81 is a Mechanism of Leukemia-Associated Macrophage Polarization in the Bone Marrow Microenvironment
Authors: Soto Celia A. , Lesch Maggie L. , Becker Jennifer L. , Sharipol Azmeer , Khan Amal , Schafer Xenia L. , Becker Michael W. , Munger Joshua C. , Frisch Benjamin J.
Published: November 2023

Interactions between acute myeloid leukemia (AML) and the bone marrow microenvironment (BMME) are critical to leukemia progression and chemoresistance. Altered metabolite levels in the tumor microenvironment contribute to immunosuppression in solid tumors, while this has not been studied yet in the leukemic BMME. Metabolomics of AML patient bone marrow serum detected elevated metabolites, including lactate, compared to age- and sex-matched controls. Excess lactate has been implicated in solid tumors for inducing suppressive tumor-associated macrophages (TAMs) and correlates with poor prognosis. We describe the role of lactate in the polarization of leukemia-associated macrophages (LAMs) using a murine model of blast crisis chronic myelogenous leukemia (bcCML) and mice genetically lacking the lactate receptor GPR81. LAMs were CD206hiand suppressive in transcriptomics and cytokine profiling. Yet, LAMs had a largely unique expression profile from other types of TAMs. We demonstrate GPR81 signaling as a mechanism of both LAM polarization and the direct support of leukemia cell growth and self-repopulation. Furthermore, LAMs and elevated lactate diminished the function of hematopoietic progenitors and stromal support, while knockout of GPR81 had modest protective effects on the hematopoietic system. We report microenvironmental lactate as a critical driver of AML-induced immunosuppression and leukemic progression, thus identifying GPR81 signaling as an exciting and novel therapeutic target for treating this devastating disease.
Cross-Sampling Rate Transfer Learning for Enhanced Raw EEG Deep Learning Classifier Performance in Major Depressive Disorder Diagnosis
Authors: Ellis Charles A. , Miller Robyn L. , Calhoun Vince D.
Published: November 2023

Transfer learning offers a route for developing robust deep learning models on small raw electroencephalography (EEG) datasets. Nevertheless, the utility of applying representations learned from large datasets with a lower sampling rate to smaller datasets with higher sampling rates remains relatively unexplored. In this study, we transfer representations learned by a convolutional neural network on a large, publicly available sleep dataset with a 100 Hertz sampling rate to a major depressive disorder (MDD) diagnosis task at a sampling rate of 200 Hertz. Importantly, we find that the early convolutional layers contain representations that are generalizable across tasks. Moreover, our approach significantly increases mean model accuracy from 82.33% to 86.99%, increases the model’s use of lower frequencies, (θ-band), and increases its robustness to channel loss. We expect this analysis to provide useful guidance and enable more widespread use of transfer learning in EEG deep learning studies.
High-throughput thermodynamic and kinetic measurements of transcription factor/DNA mutations reveal how conformational heterogeneity can shape motif selectivity
Authors: Hastings R. , Aditham A. , DelRosso N. , Suzuki P. , Fordyce P.M.
Published: November 2023

Transcription factors (TFs) bind DNA sequences with a range of affinities, yet the mechanisms determining energetic differences between high- and low-affinity sequences (‘selectivity’) remain poorly understood. Here, we investigated two basic helix-loop-helix TFs, MAX(H. sapiens)and Pho4(S. cerevisiae), that bind the same high-affinity sequence with highly similar nucleotide-contacting residues and bound structures but are differentially selective for non-cognate sequences. By measuring >1700Kds and >500 rate constants for Pho4 and MAX mutant libraries binding multiple DNA sequences and comparing these measurements with thermodynamic and kinetic models, we identify the biophysical mechanisms by which changes to TF sequence alter both bound and unbound conformational ensembles to shape specificity landscapes. These results highlight the importance of conformational heterogeneity in determining sequence specificity and selectivity and can guide future efforts to engineer nucleic acid-binding proteins with enhanced selectivity.
Peripheral nerve injury results in a biased loss of sensory neuron sub-populations
Authors: Cooper Andrew H. , Barry Allison M. , Chrysostomidou Paschalina , Lolignier Romane , Titterton Heather F. , Bennett David L. , Weir Greg A.
Published: November 2023

There is a rich literature describing loss of dorsal root ganglion (DRG) neurons following peripheral axotomy, but the vulnerability of discrete subpopulations has not yet been characterised. Furthermore, the extent and even presence of neuron loss following injury has recently been challenged. In this study, we have used a range of transgenic recombinase driver mouse lines to genetically label molecularly defined subpopulations of DRG neurons and track their survival following traumatic nerve injury. We find that spared nerve injury (SNI) leads to a marked loss of cell containing DRG-volume and a concomitant loss of small diameter DRG neurons. Neuron loss occurs unequally across subpopulations and is particularly prevalent in non-peptidergic nociceptors, marked by expression of Mrgprd. We show that this subpopulation is almost entirely lost following SNI and severely depleted (by roughly 50%) following sciatic nerve crush. Finally, we used anin vitromodel of DRG neuron survival to demonstrate that non-peptidergic nociceptor loss is likely dependent on the absence of neurotrophic support. Together, these results profile the extent to which DRG neuron subpopulations can survive axotomy, with implications for our understanding of nerve injury-induced plasticity and pain.