bluuebunny/crossref_metadata_2025 huggingface dataset:
Emulation of f(R) modified gravity from ΛCDM using conditional GANs
Authors: Gondhalekar Yash , Bose Sownak , Li Baojiu , Cuesta-Lazaro Carolina
Published: December 2024

A major aim of cosmological surveys is to test deviations from the standard $\Lambda$CDM model, but the full scientific value of these surveys will only be realized through efficient simulation methods that keep up with the increasing volume and precision of observational data. N-body simulations of modified gravity (MG) theories are computationally expensive since highly non-linear equations must be solved. This represents a significant bottleneck in the path to reach the data volume and resolution attained by equivalent $\Lambda$CDM simulations. We develop a field-level neural network-based emulator that generates density and velocity divergence fields under the $f(R)$ gravity MG model from the corresponding $\Lambda$CDM simulated fields. Using attention mechanisms and a complementary frequency-based loss function, our model is able to learn this intricate mapping. We use the idea of latent space extrapolation to generalize our emulator to $f(R)$ models with differing field strengths. The predictions of our emulator agree with the $f(R)$ simulations to within 5 per cent for matter density and to within 10  per cent for velocity divergence power spectra up to $k \sim 2\, h$$\mathrm{Mpc}^{-1}$. But for a few select cases, higher order statistics are reproduced with $\lesssim$10 per cent agreement. Latent extrapolation allows our emulator to generalize to different parametrizations of the $f(R)$ model without explicitly training on those variants. Given a $\Lambda$CDM simulation, the GPU-based emulator can reproduce the equivalent $f(R)$ realization $\sim$600 times faster than full N-body simulations. This lays the foundations for a valuable tool for realistic yet rapid mock field generation and robust cosmological analyses.
The multiple classes of ultra-diffuse galaxies: can we tell them apart?
Authors: Buzzo Maria Luisa , Forbes Duncan A , Jarrett Thomas H , Marleau Francine R , Duc Pierre-Alain , Brodie Jean P , Romanowsky Aaron J , Ferré-Mateu Anna , Hilker Michael , Gannon Jonah S , Pfeffer Joel , Haacke Lydia
Published: December 2024

This study compiles stellar populations and internal properties of ultra-diffuse galaxies (UDGs) to highlight correlations with their local environment, globular cluster (GC) richness, and star formation histories. Complementing our sample of 88 UDGs, we include 36 low surface brightness dwarf galaxies with UDG-like properties, referred to as NUDGes (nearly UDGs). All galaxies were studied using the same spectral energy distribution fitting methodology to explore what sets UDGs apart from other galaxies. We show that NUDGes are similar to UDGs in all properties except for being, by definition, smaller and having higher surface brightness. We find that UDGs and NUDGes show similar behaviours in their GC populations, with the most metal-poor galaxies hosting consistently more GCs on average. This suggests that GC content may provide an effective way to distinguish extreme galaxies within the low surface brightness regime alongside traditional parameters like size and surface brightness. We confirm previous results using clustering algorithms that UDGs split into two main classes, which might be associated with the formation pathways of a puffy dwarf and a failed galaxy. The clustering applied to the UDGs + NUDGes data set yields an equivalent result. The difference in mass contained in the GC system suggests that galaxies in different environments have not simply evolved from one another but may have formed through distinct processes.
Search for Dyson rings around pulsars: unexpected light curves
Authors: Kayali Ogetay , Haliki Emir , Bas Kubra , Nemiroff Robert J
Published: December 2024

Finding Dyson rings around distant pulsars may involve identifying light-curve features that have not been previously identified. Previous studies covered the detection of a ring structure uniformly brightened by the central pulsar, mostly in infrared light. Here, more complex light curves are explored, which arise inherently from the pulsar beam spot’s commonly predicted superluminal speed. These speeds may cause multiple images of the pulsar’s spot on the Dyson ring to appear simultaneously to a distant observer, and so feature bright creation and annihilation events. Therefore, it is possible that even if Dyson ring structures had been observed previously, they might have remained unnoticed. Similar light-curve features may appear on naturally occurring dust rings around pulsars that reflect detectable pulsar radiation.
A Descriptive Study of On-Campus Music Therapy Clinics in the United States
Authors: Schwartzberg Edward T , Silverman Michael J
Published: December 2024

Some colleges and universities with music therapy (MT) programs maintain on-campus music therapy clinics (OCMTC). Understanding how MT programs manage and operate their OCMTC may help enhance clinical training and increase access for service users in local communities. Therefore, the purpose of this study was to understand how academic programs manage and operate OCMTC. We designed an online survey divided into 3 categories: administrative (29 items), student involvement (7 items), and service users (11 items). We sent surveys to 89 MT program directors at approved academic institutions in the US. 38 participants responded to the survey, resulting in a 43% return rate. 24 respondents indicated they had an OCMTC and 2 indicated their OCMTC had closed. Respondents described an organized business approach and indicated their OCMTC provided individual and group MT sessions to a mean 45.60 (SD = 33.04) service users each week. Respondents reported a diverse clientele with the autistic community (94.12%) being the most commonly served. Nearly half of respondents used their OCMTC for student practica experiences and recruiting prospective students. Some programs integrated their OCMTC into academic coursework and class lectures. Limitations of the study and suggestions for developing and sustaining OCMTC are provided. Future research is warranted to understand how academic programs use OCMTC to prepare students and serve their communities.
Domainator, a flexible software suite for domain-based annotation and neighborhood analysis, identifies proteins involved in antiviral systems
Authors: Johnson Sean R , Weigele Peter R , Fomenkov Alexey , Ge Andrew , Vincze Anna , Eaglesham James B , Roberts Richard J , Sun Zhiyi
Published: December 2024

The availability of large databases of biological sequences presents an opportunity for in-depth exploration of gene diversity and function. Bacterial defense systems are a rich source of diverse but difficult to annotate genes with biotechnological applications. In this work, we present Domainator, a flexible and modular software suite for domain-based gene neighborhood and protein search, extraction and clustering. We demonstrate the utility of Domainator through three examples related to bacterial defense systems. First, we cluster CRISPR-associated Rossman fold (CARF) containing proteins with difficult to annotate effector domains, classifying most of them as likely transcriptional regulators and a subset as likely RNases. Second, we extract and cluster P4-like phage satellite defense hotspots, identify an abundant variant of Lamassu defense systems and demonstrate its in vivo activity against several T-even phages. Third, we integrate a protein language model into Domainator and use it to identify restriction endonucleases with low similarity to known reference sequences, validating the activity of one example in vitro. Domainator is made available as an open-source package with detailed documentation and usage examples.
Triplex H-DNA Structure: The Long and Winding Road from the Discovery to Its Role in Human Disease
Authors: Hisey Julia A , Masnovo Chiara , Mirkin Sergei M
Published: December 2024

H-DNA is an intramolecular DNA triplex formed by homopurine-homopyrimidine mirror repeats. Since its discovery, the field has advanced from characterizing the structure in vitro to discovering its existence and role in vivo. H-DNA interacts with cellular machinery in unique ways, stalling DNA and RNA polymerases and causing genome. The foundational S1 nuclease and chemical probing technologies originally used to show H-DNA formation have been updated and combined with genome-wide sequencing methods for large-scale mapping of secondary structures. There is evidence for triplex H-DNA’s role in polycystic kidney disease, cancer, and numerous repeat expansion diseases. In polycystic kidney disease (PKD), an H-DNA forming repeat region within the PKD1 gene stalls DNA replication and induces fragility. H-DNA- forming repeats in various genes have a role in cancer; the most well-studied examples involve H-DNA-mediated fragility causing translocations in multiple lymphomas. Lastly, H-DNA-forming repeats have been implicated in four repeat expansion diseases: Friedreich's ataxia (FRDA), GAA-FGF14-related ataxia, X-linked Dystonia Parkinsonism (XDP), and cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS). In this review, we summarize H-DNA’s discovery and characterization, evidence for its existence and function in vivo, and the field's current knowledge on its role in physiology and pathology.
Brain tumors and fitness to drive: A review and multi-disciplinary approach
Authors: Mondia Mark Willy L , Avila Edward K , Wefel Jeffrey S , Hehn Rachel F , Bowers Alex R , Cox Brian S , Cox Daniel J , Schiff David
Published: December 2024

Background

Patients with brain tumors and their families often inquire about driving safety. Currently, there is no consensus regarding fitness-to-drive (FTD) for patients with central nervous system tumors. Our paper aims to provide a multi-disciplinary perspective to address this issue.

Methods

We performed a literature review for brain tumors and driving. Additionally, we solicited input from experts in tumor-related epilepsy, ophthalmology, neuropsychology, occupational therapy, and driving simulators.

Results

We qualitatively analyzed 14 published articles. FTD determination varies internationally and regionally in most developed nations. Significant motor weakness and major cognitive impairment clearly prevent patients from driving. There are specialized tests for motor, vision, and cognitive correlates important to driving, but driving simulators and on-the-road tests provide the most comprehensive assessments. FTD for patients with seizures is dependent on region-specific laws that take into account the duration of seizure-free intervals and history of motor vehicular crashes.

Conclusions

We recommend a symptom-based approach that highlights the importance of interdisciplinary assessment to ensure that brain tumor patients have the minimum operational skills required to drive. It is crucial to document seizure control, visual acuity impairment, and visual field deficits because these factors usually become the default basis in practice to determine if driving privileges can be maintained. Appropriately, timed assessment of cognitive function may provide pertinent information to determine FTD. Formalized testing with practical driving evaluation may eventually be necessary in patients who have hemiparesis, hemiplegia, hemineglect, homonymous visual field loss, or any form of cognitive dysfunction to determine FTD.
Lattice plainification and band engineering lead to high thermoelectric cooling and power generation in n-type Bi2Te3 with mass production
Authors: Liu Dongrui , Bai Shulin , Wen Yi , Peng Jiayi , Liu Shibo , Shi Haonan , Li Yichen , Hong Tao , Liang Huiqiang , Qin Yongxin , Su Lizhong , Qian Xin , Wang Dongyang , Gao Xiang , Ding Zhihai , Cao Qian , Tan Qing , Qin Bingchao , Zhao Li-Dong
Published: December 2024

Thermoelectrics can mutually convert between thermal and electrical energy, ensuring its utilization in both power generation and solid-state cooling. Bi2Te3 exhibits promising room-temperature performance, making it the sole commercially available thermoelectrics to date. Guided by the lattice plainification strategy, we introduce trace amounts of Cu into n-type Bi2(Te, Se)3 (BTS) to occupy Bi vacancies, thereby simultaneously weakening defect scattering and modulating the electronic bands. Meanwhile, the interstitial Cu can bond with the BTS matrix to form extra electron transport pathways. The multiple occupations of Cu substantially boost carrier mobility and electrical performance. Consequently, the BTS + 0.2%Cu achieves a room-temperature ZT of ∼1.3 with an average ZTave of ∼1.2 at 300–523 K. Moreover, the kilogram-scale ingot designed for mass production also exhibits high uniformity. Finally, we fabricate a full-scale device that achieves an excellent conversion efficiency of ∼6.4% and a high cooling ΔTmax of ∼70.1 K, both of which outperform commercial devices.
In Children, N-Methyl-D-Aspartate Receptor Antibody Encephalitis Incidence Exceeds That of Japanese Encephalitis in Vietnam
Authors: Huong Nguyen Hoang Thien , Toan Nguyen Duc , Thien Tran Ba , Khanh Truong Huu , Tuan Nguyen Minh , Truc Tran Thanh , Nghia Nguyen An , Thinh Le Quoc , Thoa Nguyen Thi Kim , Nhan Le Nguyen Thanh , Minh Ngo Ngoc Quang , Turner Hugo C , Thwaites C Louise , Hung Nguyen Thanh , Tan Le Van , Irani Sarosh R , Quy Du Tuan
Published: December 2024

Background

The recognition of autoimmune causes of encephalitis has led to epidemiological shifts in the worldwide characteristics of encephalitis. N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis leads to well-established complex neuropsychiatric manifestations. In low- and middle-income countries, including Vietnam, its relative incidence, especially in children, is unknown and most neurologists currently consider infectious encephalitis prior to autoimmune etiologies.

Methods

The study was prospectively conducted at Children's Hospital 1 in Ho Chi Minh City between March 2020 and December 2022. Any child admitted to the Department of Infectious Diseases and Neurology fulfilling the case definition of encephalitis was eligible to participate. Cerebrospinal fluid samples were collected alongside meta-clinical data for analysis.

Results

We recruited 164 children with a clinical diagnosis of encephalitis. Etiologies were determined as NMDAR antibody encephalitis in 23 of 164 cases (14.0%), Japanese encephalitis virus in 14 of 164 (8.5%), and herpes simplex virus in 4 of 164 (2.4%). Clinical categorizations suggested idiopathic viral encephalitis in another 71 (43.3%), and autoimmune encephalitis of unknown origin in the remaining 52. Factors including demographics, specific clinical features, cerebrospinal fluid and electroencephalogram findings, and length of hospital stay were significantly different between NMDAR antibody encephalitis and Japanese encephalitis.

Conclusions

At a tertiary children's hospital in Vietnam, the prevalence of NMDAR antibody encephalitis exceeds that of Japanese encephalitis, the most common infectious encephalitis cause in Southeast Asia. NMDAR antibody encephalitis is associated with long hospital stay and poor outcomes. These findings should change pediatric diagnostics, to earlier consider autoimmune treatments in this clinical setting.
Bilayer magnetic composite systems made of random anisotropy hexaferrite and soft metallic magnets for stealth technology
Authors: Calvo-de la Rosa Jaume , López-Sánchez Jesús , Hernàndez Joan Manel , Marín Pilar , Tejada Javier
Published: December 2024

An experimental strong increase of the reflection loss (from 25 up to 35 dBs) and an extension of the absorption bandwidth up to 20% is measured in a set of novel functional bilayer systems. We focus our work on studying the samples in an anechoic chamber under far-field real radar conditions. Each layer consists of a composite material, typically a dielectric matrix filled with random anisotropy hexaferrite and soft metallic materials (powder or wires). Combining the two types of materials into a submillimetric bilayer structure has shown unprecedented improvements in microwave absorption capacities compared to the former absorption of each layer. The capacity to improve the shielding behavior is strongly related to each layer’s permittivity, permeability, and thickness leading, therefore, to a strong control over the design of novel materials for stealth applications.
Anti-Poiseuille flow by spin Hall effect
Authors: Fujimoto Junji , Koshibae Wataru , Maekawa Sadamichi
Published: December 2024

Hydrodynamics is known to emerge in electron flow when the electron–electron interaction dominates over the other momentum-nonconserving scatterings. The hydrodynamic equation that describes the electric current includes viscosity, extending beyond the Ohmic flow. The laminar flow of such a viscous electron fluid in a sample with finite width is referred to as the Poiseuille flow, where the flow velocity is maximum at the center and decreases towards the edges of the sample. In this paper, we show a unique viscous electron fluid arising in electron systems exhibiting the spin Hall effect (spin Hall systems), where the charge and spin currents are coupled. Such a viscous electron fluid emerges even in noninteracting electron systems, and the current density exhibits a minimum at the center of a flow and a maximum at the edges, i.e. an anti-Poiseuille flow realizing. We also find that the spin accumulation by the spin Hall effect is connected to the electric current vorticity in two-dimensional (2D) spin Hall systems. Furthermore, we propose a novel guiding principle to manipulate topological magnetic textures from the hydrodynamic viewpoint. By solving the hydrodynamic equation in a 2D spin Hall system with a cavity and employing micromagnetic simulations for an attached chiral magnetic insulator, we demonstrate that spin accumulation near the cavity’s boundary leads to creating a magnetic skyrmion. Our research illuminates new aspects of electron hydrodynamics and spintronics, contributing significant insights to the fields.
Fluid flow and amyloid transport and aggregation in the brain interstitial space
Authors: Iorio Antonio , Melchionna Simone , Derreumaux Philippe , Sterpone Fabio
Published: December 2024

The driving mechanisms at the base of the clearance of biological wastes in the brain interstitial space (ISS) are still poorly understood and an actively debated subject. A complete comprehension of the processes that lead to the aggregation of amyloid proteins in such environment, hallmark of the onset and progression of Alzheimer’s disease, is of crucial relevance. Here we employ combined computational fluid dynamics and molecular dynamics techniques to uncover the role of fluid flow and proteins transport in the brain ISS. Our work identifies diffusion as the principal mechanism for amyloid-β proteins clearance, whereas fluid advection may lead transport for larger molecular bodies, like amyloid-β aggregates or extracellular vesicles. We also clearly quantify the impact of large nascent prefibrils on the fluid flowing and shearing. Finally, we show that, even in the irregular brain interstitial space (ISS), hydrodynamic interactions enhance amyloid-β aggregation at all stages of the aggregation pathway. Our results are key to understand the role of fluid flow and solvent-solute interplay on therapeutics like antibodies acting in the brain ISS.
Co-evolution of risk and cooperation in climate policies under wealth inequality
Authors: Pacheco Jorge M , Santos Francisco C
Published: December 2024

Worldwide cooperation is necessary to mitigate the effects of climate change. Many previous investigations employed the so-called collective risk dilemma, where the risk of losing everything whenever a target is not met was fixed from the outset, rendering predictions dependent on snapshot values assumed for this parameter, whose importance was found to be paramount. Here, we couple risk with the overall success of mitigation, investigating the co-evolution of risk and cooperation in a world where countries are partitioned in two different wealth classes, allowing us to further assess the impact of wealth inequality and homophily on the co-evolutionary dynamics. We show that the stochastic dynamics is dominated by a global attractor, typically located in a region of low risk, where most developed countries cooperate most of the time while developing countries cooperate to a lesser extent. This scenario assumes no homophily which, when moderate, can contribute to increase overall cooperation, more so when combined with the presence of a small fraction of developing countries that opt for an unconditional cooperative behavior.
Multiscale computational model predicts how environmental changes and treatments affect microvascular remodeling in fibrotic disease
Authors: Leonard-Duke Julie , Agro Samuel M J , Csordas David J , Bruce Anthony C , Eggertsen Taylor G , Tavakol Tara N , Comlekoglu Tien , Barker Thomas H , Bonham Catherine A , Saucerman Jeffrey J , Taite Lakeshia J , Peirce Shayn M
Published: December 2024

Investigating the molecular, cellular, and tissue-level changes caused by disease, and the effects of pharmacological treatments across these biological scales, necessitates the use of multiscale computational modeling in combination with experimentation. Many diseases dynamically alter the tissue microenvironment in ways that trigger microvascular network remodeling, which leads to the expansion or regression of microvessel networks. When microvessels undergo remodeling in idiopathic pulmonary fibrosis (IPF), functional gas exchange is impaired and lung function declines. We integrated a multiscale computational model with independent experiments to investigate how combinations of biomechanical and biochemical cues in IPF alter cell fate decisions leading to microvascular remodeling. Our computational model predicted that extracellular matrix (ECM) stiffening reduced microvessel area, which was accompanied by physical uncoupling of endothelial cell (EC) and pericytes, the cells that comprise microvessels. Nintedanib, an Food and Drug Administration-approved drug for treating IPF, was predicted to further potentiate microvessel regression by decreasing the percentage of quiescent pericytes while increasing the percentage of pericytes undergoing pericyte-myofibroblast transition in high ECM stiffnesses. Importantly, the model suggested that YAP/TAZ inhibition may overcome the deleterious effects of nintedanib by promoting EC-pericyte coupling and maintaining microvessel homeostasis. Overall, our combination of computational and experimental modeling can predict and explain how cell decisions affect tissue changes during disease and in response to treatments.
Half-integer topological defects paired via string micelles in polar liquids
Authors: Ma Zhongjie , Jiang Miao , Song Yaohao , Sun Aile , Yi Shengzhu , Zhou Chao , Huang Xiang , Huang Mingjun , Aya Satoshi , Wei Qi-Huo
Published: December 2024

Ferroelectric nematic (NF) liquid crystals present a compelling platform for exploring topological defects in polar fields, while their structural properties can be significantly altered by ionic doping. In this study, we demonstrate that doping the ferroelectric nematic material RM734 with cationic polymers enables the formation of polymeric micelles that connect pairs of half-integer topological defects. Polarizing optical microscopy reveals that these string defects exhibit butterfly textures, featured with a 2D polarization field divided by Néel-type kink walls into domains exhibiting either uniform polarization or negative splay and bend deformations. Through analysis of electrophoretic motion and direct measurements of polarization divergences, we show that the string micelles are positively charged, and their side regions exhibit positive bound charges. To elucidate these observations, we propose a charge double-layer model for the string defects: the positively charged cationic polymer chains and densely packed RM734 molecules form a Stern charge layer, while small anionic ions and positive bound charges constitute the charge diffusion layer. Notably, our experiments indicate that only cationic polymer doping effectively induces the formation of these unique string defects. These findings enhance our understanding of ionic doping effects and provide valuable insights for engineering polar topologies in liquid crystal systems.
Dermal cellular senescence and EndMT in patients with systemic sclerosis undergoing cyclophosphamide or aHSCT treatment
Authors: Chiu Yu-Hsiang , van Dijk Marijke , Goldschmeding Roel , van Laar Jacob M , de Vries-Bouwstra Jeska K , Spierings Julia
Published: December 2024

Objectives

Cellular senescence and endothelial-to-mesenchymal transition (EndMT) are profibrotic cellular processes involved in systemic sclerosis (SSc), but how they respond to treatment is largely unknown.

Methods

Skin biopsies from diffuse cutaneous SSc (dcSSc) patients who underwent either autologous haematopoietic stem cell transplantation (aHSCT) or cyclophosphamide pulse (iv CYC) treatment were collected before and 6 months after randomization in the Autologous Stem Cell Transplantation International Scleroderma trial. The extent of fibrosis, inflammation, senescence, EndMT and tissue remodelling were examined in histopathology.

Results

Fourteen pairs of skin biopsies were analysed. Decrease in modified Rodnan skin score was more pronounced in aHSCT-treated patients compared with iv CYC at 6 months (median change −14 [IQR −16 to −9] vs -6 [IQR −9 to −4], respectively, P = 0.028). Histologically, expression of urokinase-type plasminogen activator receptor (uPAR) on fibroblasts, P21 on vessels and EndMT decreased after treatment in both groups, yet the reduction was more pronounced in the aHSCT group. Poor skin response was associated with high baseline connective tissue growth factor (CTGF) on fibroblasts and low baseline P21 on vessels, with an odds ratio (OR) of 1.43 and 0.41, respectively. Furthermore, poor response was also seen in patients with a rise in CTGF on fibroblasts (OR 1.29) and P21 on vessels (OR 3.02) after treatment, P < 0.001.

Conclusion

Both aHSCT and iv CYC in dcSSc reduced skin thickening clinically and attenuated EndMT, but affected cellular senescence not significantly different. EndMT and uPAR were associated with fibro-remodelling activity, whereas senescence, CTGF, uPAR and vascularity were associated with treatment response.
The commercial trust in Colombia: a massive surge
Authors: Rodríguez-Azuero Sergio
Published: December 2024

In Colombia, the commercial or mercantile contract is a vital institution for the economy’s growth and overall health. Although the figure of the trustee is limited to financial institutions authorized by the government, through the Superintendency of Finance, the contract in question is still immensely popular.
Applicability of machine learning methods for classifying lightweight pigs in commercial conditions
Authors: Salgado-López Pau , Casellas Joaquim , Solar Diaz Iara , Rathje Thomas , Gasa Josep , Solà-Oriol David
Published: December 2024

The varying growth rates within a group of pigs present a significant challenge for the current all-in-all-out systems in the pig industry. This study evaluated the applicability of statistical methods for classifying pigs at risk of growth retardation at different production stages using a robust dataset collected under commercial conditions. Data from 26,749 crossbred pigs (Yorkshire × Landrace) with Duroc at weaning (17 to 27 d), 15,409 pigs at the end of the nursery period (60 to 78 d), and 4996 pigs at slaughter (151 to 161 d) were analyzed under three different cut points (lowest 10%, 20%, and 30% weights) to characterize light animals. Records were randomly split into training and testing sets in a 2:1 ratio, and each training dataset was analyzed using an ordinary least squares approach and three machine learning algorithms (decision tree, random forest, and generalized boosted regression). The classification performance of each analytical approach was evaluated by the area under the curve (AUC). In all production stages and cut points, the random forest and generalized boosted regression models demonstrated superior classification performance, with AUC estimates ranging from 0.772 to 0.861. The parametric linear model also showed acceptable classification performance, with slightly lower AUC estimates ranging from 0.752 to 0.818. In contrast, the single decision tree was categorized as worthless, with AUC estimates between 0.608 and 0.726. Key prediction factors varied across production stages, with birthweight-related factors being most significant at weaning, and weight at previous stages becoming more crucial later in the production cycle. These findings suggest the potential of machine learning algorithms to improve decision-making and efficiency in pig production systems by accurately identifying pigs at risk of growth retardation.
Ferulic acid improves palmitate-induced insulin resistance by regulating IRS-1/Akt and AMPK pathways in L6 skeletal muscle cells
Authors: Park Jae Eun , Han Ji Sook
Published: December 2024

Objective

Increased plasma-free fatty acid (FFA) induced by obesity can trigger insulin resistance and it is a significantly dangerous constituent in the progression of diabetes. Although ferulic acid has various physiological functions, no studies have examined ferulic acid’s effects on insulin-resistant muscle cells. This study investigated the effect of ferulic acid on improving palmitic acid-induced insulin resistance in L6 skeletal muscle cells.

Methods

Palmitic acid induces insulin resistance by inhibiting the phosphorylation of IRS-1tyr and stimulating the phosphorylation of IRS-1ser in diabetes. Thus, palmitic acid (0.75 mM) was used as an insulin resistance inducer and ferulic acid was treated at various concentrations (2, 5, 10, and 20 uM) in L6 skeletal muscle cells.

Results

Palmitic acid significantly reduced the cell viability of L6 skeletal muscle cells, whereas ferulic acid treatment significantly increased cell viability in a concentration-dependent manner. Palmitic acid significantly reduced glucose uptake due to insulin resistance in the muscle cells; however, ferulic acid treatment remarkably increased glucose uptake. Ferulic acid promoted the phosphorylation of IRS-1tyr that palmitic acid inhibited, while also suppressing the palmitic acid-induced phosphorylation of IRS-1ser. Ferulic acid activated PI3K and then stimulated the phosphorylation of Akt, which increased PM-GLUT4 expression, thereby stimulating glucose uptake into insulin-resistant muscle cells. Ferulic acid also increased glycogen synthesis by phosphorylating GSK3β via the Akt pathway. Additionally, ferulic acid significantly promoted phosphorylation of AMPK, enhancing PM-GLUT4 levels and glucose uptake.

Conclusions

These results suggest that ferulic acid may improve palmitate-induced insulin resistance by regulating IRS-1/ Akt and the AMPK pathway in L6 skeletal muscle cells.
Burden of chronic obstructive pulmonary disease attributable to ambient ozone pollution across China and its provinces, 1990–2021: An analysis for the Global Burden of Disease Study 2021
Authors: Jiang Yixuan , Yan Fanshu , Kan Haidong , Zhou Maigeng , Yin Peng , Chen Renjie
Published: December 2024

Background:

Epidemiological studies have demonstrated a causal relationship between ambient ozone (O3) and mortality from chronic obstructive pulmonary disease (COPD), which is the only outcome considered in the Global Burden of Disease Study 2021 for O3. This study aims to evaluate the temporal trend and spatial distribution of the COPD burden attributable to O3 across China from 1990 to 2021.

Methods:

The ambient O3 concentrations in China were estimated. Based on the methodology framework and standard analytical methods applied in the Global Burden of Disease Study 2021, we estimated the annual number, age-standardized rate, and percentage of deaths and disability-adjusted life-years (DALYs) from COPD attributable to O3 pollution during 1990–2021 at the national and provincial levels in China.

Results:

In 2021, a total of 125.7 (95% uncertainty interval [UI], 26.4–228.3) thousand deaths and 1917.5 (95% UI, 398.7–3504.6) thousand DALYs from COPD were attributable to ambient O3 pollution in China, accounting for 9.8% (95% UI, 2.1–17.0%) and 8.1% (95% UI, 1.8–14.1%) of the total COPD deaths and DALYs, respectively. Generally, a higher burden was observed among males, the elderly, and the population residing in regions with worse health conditions. The age-standardized rates of COPD deaths and DALYs per 100,000 populations ranged from 0.5 (95% UI, 0–1.4) and 8.1 (95% UI, 0.7–20.9) in Hong Kong to 22.8 (95% UI, 3.9–43.5) and 396.6 (95% UI, 68.9–763.7) in Xizang. From 1990 to 2021, there was a notable decrease in the age-standardized rates of COPD-related deaths (68.2%, 95% UI, 60.1–74.9%) and DALYs (71.5%, 95% UI, 63.7–77.6%), especially in regions with poor health conditions. However, the attributable numbers and percentages changed relatively marginally.

Conclusions:

Ambient O3 pollution is a major contributor to the COPD burden in China. Our findings highlight the significant spatial heterogeneity across different provinces and underscore the implementation of geographically tailored policies to effectively reduce O3 pollution and alleviate the associated disease burden.
Comparative analysis of cancer statistics in China and the United States in 2024
Authors: Wu Yujie , He Siyi , Cao Mengdi , Teng Yi , Li Qianru , Tan Nuopei , Wang Jiachen , Zuo Tingting , Li Tianyi , Zheng Yuanjie , Xia Changfa , Chen Wanqing
Published: December 2024

Background:

Cancer patterns in China are becoming similar to those in the United States (US). Comparing the recent cancer profiles, trends, and determinants in China and the US can provide useful reference data.

Methods:

This study used open-source data. We used GLOBOCAN 2022 cancer estimates and United Nations population estimates to calculate cancer cases and deaths in both countries during 2024. Data on cancer incidence and mortality trends were obtained from the Surveillance, Epidemiology, and End Results (SEER) program and National Centre for Health Statistics in the US and cancer registry reports of the National Cancer Center (NCC) of China. Data from the Global Burden of Disease study (GBD) and a decomposition approach were used to estimate the contributions of four determinants to the change in cancer deaths.

Results:

In 2024, there are an estimated 3,246,625 and 2,510,597 new cancer cases and 1,699,066 and 640,038 cancer deaths in China and the US, respectively. The highest estimated cancer cases are lung cancer in China and breast cancer in the US. The age-standardized incidence rates of lung and colorectal cancer in the US, and stomach, liver, and esophageal cancer in China have decreased, but the incidence rates of liver cancer in the US and colorectal cancer, prostate cancer in men, and cervical cancer in women in China have increased. Increases in the adult population size and population aging are main reasons for the increase in cancer deaths; case fatality rates are a main reason for the decrease in cancer deaths in both countries.

Conclusions:

China has made progress in cancer control but lags the US. Considering the transformation in China’s pattern of cancers epidemiology, it is imperative to develop stronger policies by adopting the cancer prevention and control strategies used in the US to address population aging and curb growing cancer trends.
Neurologic adverse events associated with BRAF and MEK inhibitor therapy in patients with malignant melanoma: a disproportionality analysis using the Food and Drug Administration Adverse Event Reporting System
Authors: Leibovit-Reiben Zachary , Godfrey Hannah , Jedlowski Patrick , Thiede Rebecca
Published: December 2024

BRAF and MEK inhibitor (BRAFi + MEKi) therapy has improved the treatment of solid tumors with BRAF mutation. However, their neurologic adverse events (nAEs) have been largely unexplored. This study aimed to provide clinicians with more updated knowledge on nAEs associated with BRAFi + MEKi therapy in patients with malignant melanoma compared with nonmelanoma cancers. The United States Food and Drug Administration Adverse Event Reporting System was queried from 2011 to 2022 to capture nAEs reported for the BRAFi + MEKi therapies, vemurafenib plus cobimetinib (V + C), dabrafenib plus trametinib (D + T), and encorafenib plus binimetinib (E + B). A disproportionality analysis was performed to calculate their reporting odds ratios (RORs) and 95% confidence intervals (CIs) using a control group of antineoplastic medications. There were 2881 BRAFi + MEKi therapy-associated nAE cases, the majority of which listed malignant melanoma as the reason for use (87.5, 66.7, and 62.0% for V + C, D + T, and E + B, respectively). Several novel associations were identified; including epidural lipomatosis (ROR: 320.07, 95% CI: 123.76–827.77 for V + C), peripheral nerve lesion (ROR: 185.64, 95% CI: 73.95–466.03 for V + C), Guillain-Barre syndrome (RORs: 8.80, 2.94, and 11.79, 95% CIs: 3.65–21.22, 1.40–6.19, and 5.87–23.66 for V + C, D + T, and E + B), demyelinating polyneuropathy (RORs: 24.72 and 78.98, 95% CI: 8.16–74.86 and 24.84–251.13 for D + T and E + B), and multiple sclerosis (ROR: 5.90, 95% CI: 3.06–11.40 for D + T) in melanoma patients. nAEs in the setting of BRAFi + MEKi therapy should be a safety consideration when utilizing these medications.
Rate of response to immune checkpoint inhibitor therapy in patients with conjunctival melanoma
Authors: Esmaeli Bita , Ogden Tyler , Nichols Matthew , Lu Tracy , Debnam J. Matthew , Dimitriou Florentia , McQuade Jennifer , Oliva Isabella C. Glitza
Published: December 2024

Our primary objective was to estimate the overall response rate to immune checkpoint inhibitors (ICIs) in patients with locally advanced, multiply recurrent, or metastatic conjunctival melanoma treated with ICIs. A retrospective review of all consecutive conjunctival melanoma patients who were treated with ICI between October 2017 and January 2024 was carried out. The study included 16 patients with a median age of 66 years. The indications for ICI were locally extensive conjunctival melanoma in the eye/orbital area without nodal or distant metastasis in 10 patients, local recurrence of conjunctival melanoma and simultaneous nodal or distant metastasis in four patients, and metastatic conjunctival melanoma without local recurrence in two patients. Five patients received PD-1 inhibitor monotherapy with nivolumab or pembrolizumab; the other 11 received ipilimumab (CTLA-4 inhibitor) and nivolumab for several cycles and were then continued on nivolumab monotherapy (n = 6) or not given additional ICI therapy (n = 3). The number of cycles of ICI ranged from 2 to 25 (median, 13). Eight patients achieved a complete response. Six patients had progressive disease. The overall rate of objective response to ICI therapy was 63% (10 of 16), and for the subset of patients with local disease only, the objective response rate was 70% (7 of 10). In 14 patients (88%), orbital exenteration or additional extensive surgery was avoided; two patients had progression despite ICI and eventually needed an orbital exenteration. Future studies should aim to correlate biomarker data with response to ICI therapy in patients with conjunctival melanoma.
Microbiology Profiles and Antibiotic Susceptibility in Pediatric Microbial Keratitis
Authors: Cheng Melodyanne Y. , Chea Piseth Dalin , Latifi Golshan , Garner Omai B. , Deng Sophie X. , Fung Simon S. M.
Published: December 2024

Purpose:

The purpose of this study was to assess trends in microbiology profiles and antibiotic susceptibility among pediatric infectious keratitis cases in Southern California, United States.

Methods:

This is a retrospective chart review of patients aged 18 years or younger diagnosed with infectious keratitis with a positive microbiology culture between 2006 and 2019 at a tertiary academic institution. Patient demographics, microbiology results, and antibiotic susceptibilities were analyzed.

Results:

There were 23 patients included in the study period. The mean age (±SD) was 11 ± 7 years, with 60% 10 years and older. 75% were female, and 45% were of Hispanic or Latino descent. A total of 14 patients (61%) presented between June and November. A total of 30 microorganisms were identified from 24 corneal cultures of 23 eyes, and 92% were bacterial. The most common gram-positive and gram-negative isolates were Staphylococcus spp. (5/13, 38%) and Pseudomonas spp. (9/15, 60%), respectively. 92.3% gram-positive isolates were susceptible to vancomycin, but only 7.7% were susceptible to erythromycin. Gram-negative isolates were susceptible to gentamicin (86%), ciprofloxacin (79%), and ceftazidime (55%). Pseudomonas spp. was highly susceptible to gentamicin (100%) and ciprofloxacin (83%), and it was moderately susceptible to tobramycin (44%) and ceftazidime (67%).

Conclusions:

Pediatric microbial keratitis cases in Southern California were predominantly bacterial infections, with gram-positive isolates highly susceptible to vancomycin and gram-negative isolates, particularly Pseudomonas spp., showing high susceptibility to gentamicin and ciprofloxacin.
Pediatric Anterior Cruciate Ligament Tears
Authors: Stinson Zachary , Fink Julia
Published: December 2024

Anterior cruciate ligament (ACL) tears have become an increasingly prevalent problem in pediatric patients due to increased youth sports participation and early sports specialization. A high index of suspicion should be utilized for any young patient with an acute knee injury and an associated effusion or difficulty bearing weight. A thorough work-up should be performed that includes a careful assessment of growth remaining and concomitant injuries. While nonoperative management may be a consideration for select cases, most patients will benefit from early surgical management. ACL deficiency or delayed reconstruction can lead to early chondral degeneration and risk for further injury to the cartilage and menisci. The goal of ACL reconstruction is to create a stable knee and prevent secondary chondral or meniscal injury. Physeal-sparing and physeal-respecting transphyseal techniques have been developed that allow for safe and successful ligament reconstruction while minimizing the risk of growth arrest. Younger patients have a higher risk of reinjury and require a longer recovery period for a full return to sports than their older counterparts. Even though there have been advances in the safe and successful treatment of ACL tears in pediatric patients, it remains a devastating physical and psychological injury, and increased efforts should be made at prevention. Injury prevention programs have been shown to reduce the risk of ACL tears, and it is important to increase awareness and utilization of prevention strategies.
Acute Lung Injury
Authors: Verma Nupur , Hochhegger Bruno , Mukhopadhyay Sanjay , Teixeira e Silva Torres Pedro Paulo , Mohammed Tan-Lucien
Published: December 2024

Acute lung injury (ALI) is acute pulmonary inflammation with underlying pathology of disruption of the pulmonary vasculature endothelial and alveolar epithelial barriers. ALI is not an uncommon diagnosis and has a myriad of causes including pulmonary infection, (including sepsis), drugs, connective tissue disease, and polytrauma. Patients present clinically with hypoxemia with imaging supportive of bilateral pulmonary findings without pulmonary edema. The imaging findings in ALI mirror pathologic changes, with a transition from an early (“exudative”) phase to a later fibroblast-rich (“organizing” or “proliferative”) phase to, in some cases, a fibrotic phase. The diagnosis of ALI is separate from, but can clinically overlap in presentation with, acute respiratory distress syndrome and is characterized by diffuse alveolar damage and organizing pneumonia patterns on pathology. Clinical management is most often supportive and can include corticosteroids, mechanical ventilation, and careful fluid management, with the goal of preserving and recovering lung function.
Optimal Time for Nevus Sebaceous Excision and Predictors of Surgical Outcomes and Secondary Intralesional Neoplasms: The Mayo Clinic Experience Over 37 Years
Authors: Meira Pazelli Alexandre , Cherukuri Sai K. , Davis Dawn M R. , Mardini Samir , Bite Uldis , Vierkant Robert A. , Mandrekar Jay , Lehman Julia S. , Gibreel Waleed
Published: December 2024

Background:

Controversy exists around the optimal timing of resection of nevus sebaceous (NS). The authors aim to determine optimal timing of NS resection and identify predictors of surgical outcomes and secondary intralesional neoplasms.

Methods:

Retrospective chart review of all patients with biopsy-proven NS diagnosis treated at the authors' institution between 1987 and 2024.

Results:

A total of 632 patients (317 females) underwent biopsy at a median age of 17 (interquartile range 11.7–36.9) years. Benign secondary intralesional neoplasms were found in 67 (10.6%) patients, with syringocystadenoma papilliferum being the most common. Malignant secondary intralesional neoplasms were diagnosed in 62 (9.8%) patients, with basal cell carcinoma being the most common. The incidence of secondary intralesional neoplasms was 3.9%, 24.4%, 36.05%, and 54%, in patients aged 0 to 20, 20 to 40, 40 to 60, and 60 to 80 years, respectively (P<0.001). Age and NS area were associated with an increased risk of developing benign and malignant intralesional neoplasms (P=0.01). Younger patients were more likely to need general anesthesia for excision (median age 10.42 versus 17 years, P<0.001). Surgical complications occurred in 10 cases, and 6 patients required unanticipated revision surgery. The risk of developing secondary intralesional neoplasms was similar across different NS anatomic regions (log-rank, P=0.09).

Conclusion:

Surgical excision of NS is safe and has an acceptable risk profile. The findings of this study support our historic practice of NS excision before puberty (before the accelerated growth phase) to reduce the risk of developing secondary intralesional neoplasms.
The Scarab Technique for Correction of Late-Presenting Sagittal Suture Craniosynostosis
Authors: Fortoul Marla C. , Oualid Chaimae , Stella John , Roca Andrea , Stelnicki Eric J. , Kamel George N.
Published: December 2024

Introduction:

Sagittal synostosis (SS) is the most prevalent form of craniosynostosis. It is the premature fusion of the sagittal suture, resulting in a “boat like” skull shape. Early surgical intervention is crucial to prevent complications, yet no standard procedure exists for patients over 12 months old. This study introduces the “Scarab technique”, a novel surgical approach for late-presenting SS cases diagnosed after 1 year of age.

Methods:

A single-center, board-approved retrospective review was conducted from May 2017 to June 2020. The Scarab technique was used exclusively for delayed SS diagnosed after 1 year old. A 4 cm craniectomy was outlined around the sagittal suture, and vascularized scarab bone flaps attached to the parietal bone vasculature were created. These extension flaps were then lifted for further biparietal and bitemporal expansion, followed by an occipital-type advancement and fixation with resorbable plates and screws.

Results:

A total of 7 patients with delayed sagittal synostosis diagnosis underwent scarab technique surgery. The majority were male (71%) and Caucasian (43%). Mean surgery age was 2.6 years (SD=1.3), with 3.43-hour average operation time (SD=0.86), 101.4 mL estimated blood loss (SD=54.5), 3.85 days in the PICU (SD=0.69), and only 1 patient with a resolved postoperative infection.

Conclusions:

The Scarab technique is an effective alternative for treating delayed sagittal craniosynostosis, yielding statistically significant improvements in head shape and overall development post-surgery. Further long-term analysis and multicenter comparative studies with alternative techniques are warranted to fully assess its efficacy and outcomes.