bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy-efficient neural network using an anisotropy field gradient-based self-resetting neuron and meander synapse
Authors: Dhull Seema , Mah Wai Lum William , Nisar Arshid , Kumar Durgesh , Rahaman Hasibur , Kaushik Brajesh Kumar , Piramanayagam S. N.
Published: July 2024

Neuromorphic computing (NC) is considered a potential solution for energy-efficient artificial intelligence applications. The development of reliable neural network (NN) hardware with low energy and area footprints plays a crucial role in realizing NC. Even though neurons and synapses have already been investigated using a variety of spintronic devices, the research is still in the primitive stages. Particularly, there is not much experimental research on the self-reset (and leaky) aspect(s) of domain wall (DW) device-based neurons. Here, we have demonstrated an energy-efficient NN using a spintronic DW device-based neuron with self-reset (leaky) and integrate-and-fire functions. An “anisotropy field gradient” provides the self-resetting behavior of auto-leaky, integrate, and fire neurons. The leaky property of the neuron was experimentally demonstrated using a voltage-assisted modification of the anisotropy field. A synapse with a meander wire configuration was used to achieve multiple-resistance states corresponding to the DW position and controlled pinning of the DW. The NN showed an energy efficiency of 0.189 nJ/image/epoch while achieving an accuracy of 92.4%. This study provides a fresh path for developing more energy-efficient DW-based NN systems.
Arecibo STEM educational center to open soon
Authors: Means Hannah H.
Published: July 2024

Biology and computer science activities replace the iconic radio telescope at the Puerto Rican observatory site.
Global impacts of an extreme solar particle event under different geomagnetic field strengths
Authors: Arsenović Pavle , Rozanov Eugene , Usoskin Ilya , Turney Chris , Sukhodolov Timofei , McCracken Ken , Friedel Marina , Anet Julien , Simić Stana , Maliniemi Ville , Egorova Tatiana , Korte Monika , Rieder Harald , Cooper Alan , Peter Thomas
Published: July 2024

Solar particle events (SPEs) are short-lived bursts of high-energy particles from the solar atmosphere and are widely recognized as posing significant economic risks to modern society. Most SPEs are relatively weak and have minor impacts on the Earth’s environment, but historic records contain much stronger SPEs which have the potential to alter atmospheric chemistry, impacting climate and biological life. The impacts of such strong SPEs would be far more severe when the Earth’s protective geomagnetic field is weak, such as during past geomagnetic excursions or reversals. Here, we model the impacts of an extreme SPE under different geomagnetic field strengths, focusing on changes in atmospheric chemistry and surface radiation using the atmosphere–ocean–chemistry–climate model SOCOL3-MPIOM and the radiation transfer model LibRadtran. Under current geomagnetic conditions, an extreme SPE would increase NOxconcentrations in the polar stratosphere and mesosphere, causing reductions in extratropical stratospheric ozone lasting for about a year. In contrast, with no geomagnetic field, there would be a substantial increase in NOxthroughout the entire atmosphere, resulting in severe stratospheric ozone depletion for several years. The resulting ground-level ultraviolet (UV) radiation would remain elevated for up to 6 y, leading to increases in UV index up to 20 to 25% and solar-induced DNA damage rates by 40 to 50%. The potential evolutionary impacts of past extreme SPEs remain an important question, while the risks they pose to human health in modern conditions continue to be underestimated.
Private management of African protected areas improves wildlife and tourism outcomes but with security concerns in conflict regions
Authors: Denny Sean , Englander Gabriel , Hunnicutt Patrick
Published: July 2024

Protected areas can conserve wildlife and benefit people when managed effectively. African governments increasingly delegate the management of protected areas to private, nongovernmental organizations, hoping that private organizations’ significant resources and technical capacities actualize protected areas’ potential. Does private sector management improve outcomes compared to a counterfactual of government management? We leverage the transfer of management authority from governments to African Parks (AP)—the largest private manager of protected areas in Africa—to show that private management significantly improves wildlife outcomes via reduced elephant poaching and increased bird abundances. Our results also suggest that AP’s management augments tourism, while the effect on rural wealth is inconclusive. However, AP’s management increases the risk of armed groups targeting civilians, which could be an unintended outcome of AP’s improved monitoring and enforcement systems. These findings reveal an intricate interplay between conservation, economic development, and security under privately managed protected areas in Africa.
DNA polymerase κ participates in early S-phase DNA replication in human cells
Authors: Tang Feng , Wang Yinan , Zhao Ting , Yuan Jun , Kellum Andrew H. , Wang Yinsheng
Published: July 2024

Cycling cells replicate their DNA during the S phase through a defined temporal program known as replication timing. Mutation frequencies, epigenetic chromatin states, and transcriptional activities are different for genomic regions that are replicated early and late in the S phase. Here, we found from ChIP-Seq analysis that DNA polymerase (Pol) κ is enriched in early-replicating genomic regions in HEK293T cells. In addition, by feeding cells with
N
 2
-heptynyl-2′-deoxyguanosine followed by click chemistry–based enrichment and high-throughput sequencing, we observed elevated Pol κ activities in genomic regions that are replicated early in the S phase. On the basis of the established functions of Pol κ in accurate and efficient nucleotide insertion opposite endogenously induced
N
 2
-modified dG lesions, our work suggests that active engagement of Pol κ may contribute to diminished mutation rates observed in early-replicating regions of the human genome, including cancer genomes. Together, our work expands the functions of Pol κ and offered a plausible mechanism underlying replication timing–dependent mutation accrual in the human genome.
Impact of various DIII-D diagnostics on the accuracy of neural network surrogates for kinetic EFIT reconstructions
Authors: Sun Xuan , Akçay Cihan , Bechtel Amara Torrin , Kruger Scott E , Lao Lang L , Liu Yueqiang , Madireddy Sandeep , McClenaghan Joseph ,   the EFIT-AI Team
Published: July 2024

Kinetic equilibrium reconstructions make use of profile information such as particle density and temperature measurements in addition to magnetics data to compute a self-consistent equilibrium. They are used in a multitude of physics-based modeling. This work develops a multi-layer perceptron (MLP) neural network (NN) model as a surrogate for kinetic Equilibrium Fitting (EFITs) and trains on the 2019 DIII-D discharge campaign database of kinetic equilibrium reconstructions. We investigate the impact of including various diagnostic data and machine actuator controls as input into the NN. When giving various categories of data as input into NN models that have been trained using those same categories of data, the predictions on multiple equilibrium reconstruction solutions (poloidal magnetic flux, global scalars, pressure profile, current profile) are highly accurate. When comparing different models with different diagnostics as input, the magnetics-only model outputs accurate kinetic profiles and the inclusion of additional data does not significantly impact the accuracy. When the NN is tasked with inferring only a single target such as the EFIT pressure profile or EFIT current profile, we see a large increase in the accuracy of the prediction of the kinetic profiles as more data is included. These results indicate that certain MLP NN configurations can be reasonably robust to different burning-plasma-relevant diagnostics depending on the accuracy requirements for equilibrium reconstruction tasks.
A guide to moduli theory beyond GIT
Authors: Gómez Tomás , Fernández Herrero Andres , Zamora Alfonso
Published: July 2024

In this survey we provide an overview of some recent developments in the construction of moduli spaces using stack-theoretic techniques. We will also explain the analogue of Harder-Narasimhan stratifications for general stacks, known as

Θ
\Theta

-stratifications. As an application of the ideas exposed here, we address the moduli problem of principal bundles over higher dimensional projective varieties, as well as its different compactifications by the so-called principal

ρ
\rho

-sheaves. We construct a stratification by instability types whose lower strata admits a proper good moduli space of “Gieseker semistable” objects and a new Gieseker-type Harder-Narasimhan filtration for these objects. Detailed proofs of the latter results will appear elsewhere.
Joint associations of diet and physical activity with incident type 2 diabetes and hypertension: an analysis of 144 288 UK Biobank participants
Authors: Inan-Eroglu Elif , Ahmadi Matthew , Sainsbury Amanda , Leitzmann Michael , Khunti Kamlesh , Yates Thomas , Stamatakis Emmanuel
Published: July 2024

Studies examining the joint associations of lifestyle exposures can reveal novel synergistic and joint effects, but no study has examined the joint association of diet and physical activity (PA) with type 2 diabetes (T2D) and hypertension. The aim of this study is to examine the joint associations of PA and diet with incidence of type T2D and hypertension, as a combined outcome and separately in a large sample of adults in the United Kingdom. This prospective cohort study included 144 288 UK Biobank participants aged 40-69. Moderate to vigorous PA (MVPA) was measured using the International Physical Activity Questionnaire and a wrist accelerometer. We categorized PA and diet indicators (diet quality score [DQS] and energy intake [EI]) based on tertiles and derived joint PA and diet variables. Outcome was major cardiometabolic disease incidence (combination of T2D and hypertension). A total of 14 003 (7.1%) participants developed T2D, 28 075 (19.2%) developed hypertension, and 30 529 (21.2%) developed T2D or hypertension over a mean follow-up of 10.9 (3.7) years. Participants with middle and high self-reported MVPA levels had lower risk of major cardiometabolic disease regardless of diet (eg, among high DQS group, hazard ratios [HRs] in middle and high MVPA group were 0.90; 95% CI, 0.86-0.94), and 0.88 (95% CI, 0.84-0.92), respectively. Participants with jointly high device-measured MVPA and high DQS levels had lower major cardiometabolic disease risk (HR, 0.84; 95% CI, 0.71-0.99). The equivalent joint device-measured MVPA and EI exposure analyses showed no clear pattern of associations with the outcomes. Higher PA is an important component in cardiometabolic disease prevention across all diet quality and total EI groups. The observed lack of association between diet health outcomes may stem from a lower DQS.
DeepGSEA: explainable deep gene set enrichment analysis for single-cell transcriptomic data
Authors: Xiong Guangzhi , LeRoy Nathan J , Bekiranov Stefan , Sheffield Nathan C , Zhang Aidong
Published: July 2024

Motivation

Gene set enrichment (GSE) analysis allows for an interpretation of gene expression through pre-defined gene set databases and is a critical step in understanding different phenotypes. With the rapid development of single-cell RNA sequencing (scRNA-seq) technology, GSE analysis can be performed on fine-grained gene expression data to gain a nuanced understanding of phenotypes of interest. However, with the cellular heterogeneity in single-cell gene profiles, current statistical GSE analysis methods sometimes fail to identify enriched gene sets. Meanwhile, deep learning has gained traction in applications like clustering and trajectory inference in single-cell studies due to its prowess in capturing complex data patterns. However, its use in GSE analysis remains limited, due to interpretability challenges.

Results

In this paper, we present DeepGSEA, an explainable deep gene set enrichment analysis approach which leverages the expressiveness of interpretable, prototype-based neural networks to provide an in-depth analysis of GSE. DeepGSEA learns the ability to capture GSE information through our designed classification tasks, and significance tests can be performed on each gene set, enabling the identification of enriched sets. The underlying distribution of a gene set learned by DeepGSEA can be explicitly visualized using the encoded cell and cellular prototype embeddings. We demonstrate the performance of DeepGSEA over commonly used GSE analysis methods by examining their sensitivity and specificity with four simulation studies. In addition, we test our model on three real scRNA-seq datasets and illustrate the interpretability of DeepGSEA by showing how its results can be explained.

Availability and implementation

https://github.com/Teddy-XiongGZ/DeepGSEA
Toward acid- and heparin-free dialysis: the regional anticoagulation approach
Authors: Lefevre Flora , Vial Romain , Grellier Sophie , Bujon Solène , Bouchouareb Dammar , Brunet Philippe , Scarfoglière Violaine , Robert Thomas
Published: July 2024

Background

In chronic intermittent hemodialysis, heparin is the standard anticoagulant as is the use of acid-containing dialysate. Regional anticoagulation (RA) with a calcium-free, citrate-containing dialysate has been developed. We compared RA using a calcium-free, citrate-free dialysate, routinely used in our center, versus systemic heparinization.

Methods

In a retrospective, observational, single-center, crossover study, we examined 15 patients undergoing chronic hemodialysis who were at high risk of bleeding and temporarily unable to use heparin. These patients received temporary treatment with RA involving calcium-free and citrate-free dialysate. We compared the dialysis session success rates during two distinct periods: standard heparinization and RA procedure with a calcium-free and citrate-free dialysate.

Results

In our study of 15 patients on chronic hemodialysis which compared 30 RA sessions versus 28 heparin-based anticoagulation session, we observed a 100% success rate with a median session duration of 240 min in both RA and heparin groups. No early extracorporeal circulation (ECC) loss was reported. However, we noted significant differences in the post-dialysis ECC thrombosis scores, with higher Global Thrombosis Index (GTI) and higher membrane coagulation scores in the RA group (P < .007 and P < .02, respectively). No hypocalcaemia or hypercalcemia symptoms occurred. Median post-filter ionized calcium levels were 0.32 (0.29–0.39) mmol/L at 30 min and median patient ionized calcium levels was 1.19 (1.135–1.28) mmol/L at 60 min. No significant difference in per-dialysis arterial blood pressure was observed between groups.

Conclusion

Our study evaluated the RA approach using a calcium-free, citrate-free acetate dialysate in a chronic hemodialysis center and found it effective. Although an acid-free dialysate was not used in this study, our findings suggest it could be the next frontier in the evolution of advanced dialysis techniques.
Parity, infertility, age at first birth, and risk of atrial fibrillation: data from the HUNT study
Authors: Morooka Hikaru , Haug Eirin B , Malmo Vegard , Loennechen Jan Pål , Mukamal Kenneth J , Sen Abhijit , Janszky Imre , Horn Julie
Published: July 2024

Aims

Although parity, infertility, and age at first birth are important for later development of cardiovascular disease, research on their association with atrial fibrillation (AF) is limited.

Methods and results

We linked data from the population-based HUNT study and the Medical Birth Registry of Norway (MBRN) and validated medical records from local hospitals. A total of 24 015 women aged 45 years or older were followed for verified incident AF. Parity and age at first birth were retrieved from the MBRN or from self-reported questionnaires in the HUNT study. A history of infertility was self-reported on the HUNT questionnaire. Cox proportional hazards models were used to calculate hazard ratios (HRs) for the multivariable-adjusted associations of parity, infertility, and age at first birth with risk of AF. During a median follow-up of 12.8 years, 1448 (6.0%) participants developed AF. Women with higher parity (four or more births vs. two births) were at 21% higher risk of AF [HR 1.21, 95% confidence interval (CI) 1.05–1.39]. A history of infertility was also associated with the risk of AF (HR 1.20, 95% CI 1.02–1.42). Among parous women, younger age at first birth (<20 vs. 20–29 years) was associated with a 20% higher risk of AF (HR 1.20, 95% CI 1.03–1.40).

Conclusion

Women with four or more births, or a history of infertility, or younger age at first birth have approximately a 20% higher risk of AF among women over 45 years old.
A pilot clinical risk model to predict polymyxin-induced nephrotoxicity: a real-world, retrospective cohort study
Authors: Song Mong-Hsiu , Xiang Bi-Xiao , Yang Chien-Yi , Lee Chou-Hsi , Yan Yu-Xuan , Yang Qin-Jie , Yin Wen-Jun , Zhou Yangang , Zuo Xiao-Cong , Xie Yue-Liang
Published: July 2024

Objectives

Polymyxin-induced nephrotoxicity (PIN) is a major safety concern and challenge in clinical practice, which limits the clinical use of polymyxins. This study aims to investigate the risk factors and to develop a scoring tool for the early prediction of PIN.

Methods

Data on critically ill patients who received intravenous polymyxin B or colistin sulfate for over 24 h were collected. Logistic regression with the least absolute shrinkage and selection operator (LASSO) was used to identify variables that are associated with outcomes. The eXtreme Gradient Boosting (XGB) classifier algorithm was used to further visualize factors with significant differences. A prediction model for PIN was developed through binary logistic regression analysis and the model was assessed by temporal validation and external validation. Finally, a risk-scoring system was developed based on the prediction model.

Results

Of 508 patients, 161 (31.6%) patients developed PIN. Polymyxin type, loading dose, septic shock, concomitant vasopressors and baseline blood urea nitrogen (BUN) level were identified as significant predictors of PIN. All validation exhibited great discrimination, with the AUC of 0.742 (95% CI: 0.696–0.787) for internal validation, of 0.708 (95% CI: 0.605–0.810) for temporal validation and of 0.874 (95% CI: 0.759–0.989) for external validation, respectively. A simple risk-scoring tool was developed with a total risk score ranging from −3 to 4, corresponding to a risk of PIN from 0.79% to 81.24%.

Conclusions

This study established a prediction model for PIN. Before using polymyxins, the simple risk-scoring tool can effectively identify patients at risk of developing PIN within a range of 7% to 65%.
Molecular characterization of macrolide resistance in Haemophilus influenzae and Haemophilus parainfluenzae strains (2018–21)
Authors: Cadenas-Jiménez Irene , Saiz-Escobedo Lucía , Carrera-Salinas Anna , Camprubí-Márquez Xenia , Calvo-Silveria Sara , Camps-Massa Paula , Berbel Dàmaris , Tubau Fe , Santos Salud , Domínguez M Angeles , González-Díaz Aida , Ardanuy Carmen , Martí Sara
Published: July 2024

Objectives

This study aimed to explore the prevalence of macrolide resistance and the underlying resistance mechanisms in Haemophilus influenzae (n = 2556) and Haemophilus parainfluenzae (n = 510) collected between 2018 and 2021 from Bellvitge University Hospital, Spain.

Methods

Antimicrobial susceptibility was tested by microdilution. Whole-genome sequencing was performed using Illumina MiSeq and Oxford Nanopore technologies, and sequences were examined for macrolide resistance determinants and mobile genetic structures.

Results

Macrolide resistance was detected in 67 H. influenzae (2.6%) and 52 (10.2%) H. parainfluenzae strains and associated with resistance to other antimicrobials (co-trimoxazole, chloramphenicol, tetracycline). Differences in macrolide resistance existed between the two species. Acquired resistance genes were more prevalent in H. parainfluenzae (35/52; 67.3%) than in H. influenzae (12/67; 17.9%). Gene mutations and amino acid substitutions were more common in H. influenzae (57/67; 85%) than in H. parainfluenzae (16/52; 30.8%). Substitutions in L22 and in 23S rRNA were only detected in H. influenzae (34.3% and 29.0%, respectively), while substitutions in L4 and AcrAB/AcrR were observed in both species. The MEGA element was identified in 35 (67.3%) H. parainfluenzae strains, five located in an integrative and conjugative element (ICE); by contrast, 11 (16.4%) H. influenzae strains contained the MEGA element (all in an ICE). A new ICEHpaHUB8 was described in H. parainfluenzae.

Conclusions

Macrolide resistance was higher in H. parainfluenzae than in H. influenzae, with differences in the underlying mechanisms. H. parainfluenzae exhibits co-resistance to other antimicrobials, often leading to an extensively drug-resistant phenotype. This highlights the importance of conducting antimicrobial resistance surveillance.
Completeness and readability of GPT-4-generated multilingual discharge instructions in the pediatric emergency department
Authors: Gimeno Alex , Krause Kevin , D’Souza Starina , Walsh Colin G
Published: July 2024

Objectives

The aim of this study was to assess the completeness and readability of generative pre-trained transformer-4 (GPT-4)-generated discharge instructions at prespecified reading levels for common pediatric emergency room complaints.

Materials and Methods

The outputs for 6 discharge scenarios stratified by reading level (fifth or eighth grade) and language (English, Spanish) were generated fivefold using GPT-4. Specifically, 120 discharge instructions were produced and analyzed (6 scenarios: 60 in English, 60 in Spanish; 60 at a fifth-grade reading level, 60 at an eighth-grade reading level) and compared for completeness and readability (between language, between reading level, and stratified by group and reading level). Completeness was defined as the proportion of literature-derived key points included in discharge instructions. Readability was quantified using Flesch-Kincaid (English) and Fernandez-Huerta (Spanish) readability scores.

Results

English-language GPT-generated discharge instructions contained a significantly higher proportion of must-include discharge instructions than those in Spanish (English: mean (standard error of the mean) = 62% (3%), Spanish: 53% (3%), P = .02). In the fifth-grade and eighth-grade level conditions, there was no significant difference between English and Spanish outputs in completeness. Readability did not differ across languages.

Discussion

GPT-4 produced readable discharge instructions in English and Spanish while modulating document reading level. Discharge instructions in English tended to have higher completeness than those in Spanish.

Conclusion

Future research in prompt engineering and GPT-4 performance, both generally and in multiple languages, is needed to reduce potential for health disparities by language and reading level.
Modification to the Jeans criterion by external tides: anisotropic fragmentation and formation of filaments
Authors: Li Guang-Xing
Published: July 2024

The Jeans criterion sets the foundation of our understanding of gravitational collapse. Jog studied the fragmentation of gas under external tides and derived a dispersion relation $l^{\prime } = l_{\rm Jeans} \frac{1}{(1 + \lambda _0^{\prime } / 4 \pi G \rho _0)^{1/2}} \,\,.$ She further concludes that the Jeans mass is $m_{\rm incorrect}^{\prime }=m_{\rm Jeans} [1/(1 + \lambda _0^{\prime } / 4 \pi G \rho _0)^{3/2}]$. We clarify that due to the inhomogeneous nature of tides, this characteristic mass is incorrect. Under weak tides, the mass is $m \approx \rho \, l_1 l_2 l_3$, where the modifications to Jeans lengths along all three dimensions need to be considered; when the tide is strong enough, collapse can only occur once 1 or 2 dimensions. In the latter case, tides can stretch the gas, leading to the formation of filaments.
Velcrin molecular glues induce apoptosis in glioblastomas with high PDE3A and SLFN12 expression
Authors: Aquilanti Elisa , Goldoni Silvia , Baker Andrew , Kotynkova Kristyna , Andersen Sawyer , Bozinov Vincent , Gao Galen F , Cherniack Andrew D , Lange Martin , Lesche Ralf , Kopitz Charlotte , Lienau Philip , Lewis Timothy A , Garrido Marine , Gradl Stefan , Seidel Henrik , Tseng Yuen-Yi , Ligon Keith L , Wen Patrick Y , Meyerson Matthew , Greulich Heidi
Published: July 2024

Background

Velcrins are molecular glues that kill cells by inducing the formation of a protein complex between the RNase SLFN12 and the phosphodiesterase PDE3A. Formation of the complex activates SLFN12, which cleaves tRNALeu(TAA) and induces apoptosis. Velcrins such as the clinical investigational compound, BAY 2666605, were found to have activity across multiple solid tumor cell lines from the cancer cell line encyclopedia, including glioblastoma cell lines. We therefore aim to characterize velcrins as novel therapeutic agents in glioblastoma.

Materials and Methods

PDE3A and SLFN12 expression levels were measured in glioblastoma cell lines, the Cancer Genome Atlas (TCGA) tumor samples, and tumor neurospheres. Velcrin-treated cells were assayed for viability, induction of apoptosis, cell cycle phases, and global changes in translation. Transcriptional profiling of the cells was obtained. Xenograft-harboring mice treated with velcrins were also monitored for survival.

Results

We identified several velcrin-sensitive glioblastoma cell lines and 4 velcrin-sensitive glioblastoma patient-derived models. We determined that BAY 2666605 crosses the blood-brain barrier and elicits full tumor regression in an orthotopic xenograft model of GB1 cells. We also determined that the velcrins BAY 2666605 and BRD3800 induce tumor regression in subcutaneous glioblastoma PDX models.

Conclusions

Velcrins have antitumor activity in preclinical models of glioblastoma, warranting further investigation as potential therapeutic agents.
Enhanced radiation sensitivity, decreased DNA damage repair, and differentiation defects in airway stem cells derived from patients with chronic obstructive pulmonary disease
Authors: Giuranno Lorena , Piepers Jolanda A F , Korsten Evelien , Borman Reitske , van de Kamp Gerarda , De Ruysscher Dirk , Essers Jeroen , Vooijs Marc A
Published: July 2024

Radiation therapy (RT) is a common treatment for lung cancer. Still, it can lead to irreversible loss of pulmonary function and a significant reduction in quality of life for one-third of patients. Preexisting comorbidities, such as chronic obstructive pulmonary disease (COPD), are frequent in patients with lung cancer and further increase the risk of complications. Because lung stem cells are crucial for the regeneration of lung tissue following injury, we hypothesized that airway stem cells from patients with COPD with lung cancer might contribute to increased radiation sensitivity. We used the air-liquid interface model, a three-dimensional (3D) culture system, to compare the radiation response of primary human airway stem cells from healthy and patients with COPD. We found that COPD-derived airway stem cells, compared to healthy airway stem cell cultures, exhibited disproportionate pathological mucociliary differentiation, aberrant cell cycle checkpoints, residual DNA damage, reduced survival of stem cells and self-renewal, and terminally differentiated cells post-irradiation, which could be reversed by blocking the Notch pathway using small-molecule γ-secretase inhibitors. Our findings shed light on the mechanisms underlying the increased radiation sensitivity of COPD and suggest that airway stem cells reflect part of the pathological remodeling seen in lung tissue from patients with lung cancer receiving thoracic RT.
Integrating Genomics and Biogeography to Unravel the Origin of a Mountain Biota: The Case of a Reptile Endemicity Hotspot in Arabia
Authors: Burriel-Carranza Bernat , Tejero-Cicuéndez Héctor , Carné Albert , Mochales-Riaño Gabriel , Talavera Adrián , Al Saadi Saleh , Els Johannes , Šmíd Jiří , Tamar Karin , Tarroso Pedro , Carranza Salvador
Published: July 2024

Advances in genomics have greatly enhanced our understanding of mountain biodiversity, providing new insights into the complex and dynamic mechanisms that drive the formation of mountain biotas. These span from broad biogeographic patterns to population dynamics and adaptations to these environments. However, significant challenges remain in integrating large-scale and fine-scale findings to develop a comprehensive understanding of mountain biodiversity. One significant challenge is the lack of genomic data, especially in historically understudied arid regions where reptiles are a particularly diverse vertebrate group. In the present study, we assembled a de novo genome-wide SNP dataset for the complete endemic reptile fauna of a mountain range (19 described species with more than 600 specimens sequenced), and integrated state-of-the-art biogeographic analyses at the population, species, and community level. Thus, we provide a holistic integration of how a whole endemic reptile community has originated, diversified and dispersed through a mountain system. Our results show that reptiles independently colonized the Hajar Mountains of southeastern Arabia 11 times. After colonization, species delimitation methods suggest high levels of within-mountain diversification, supporting up to 49 deep lineages. This diversity is strongly structured following local topography, with the highest peaks acting as a broad barrier to gene flow among the entire community. Interestingly, orogenic events do not seem key drivers of the biogeographic history of reptiles in this system. Instead, past climatic events seem to have had a major role in this community assemblage. We observe an increase of vicariant events from Late Pliocene onwards, coinciding with an unstable climatic period of rapid shifts between hyper-arid and semiarid conditions that led to the ongoing desertification of Arabia. We conclude that paleoclimate, and particularly extreme aridification, acted as a main driver of diversification in arid mountain systems which is tangled with the generation of highly adapted endemicity. Overall, our study does not only provide a valuable contribution to understanding the evolution of mountain biodiversity, but also offers a flexible and scalable approach that can be reproduced into any taxonomic group and at any discrete environment.
Czech Republic: Czech private foundations and trusts in the light of recent discussions and case law
Authors: Pihera Vlastimil , Ronovská Kateřina
Published: July 2024

This article aims to summarize, in the context of recent court decisions (case law), the development of the views and concepts with which private foundations and trusts have been viewed in Czech law over the last 10 years. In this respect, the authors believe that Czech law can serve as a kind of (albeit imperfect) laboratory for exploring the general difficulties encountered by traditional civil law jurisdictions in introducing these wealth management instruments institutes into traditional civil law systems.
LncRNA HILPDA promotes contrast-induced acute kidney injury by recruiting eIF4B to upregulate XPO1 expression
Authors: Wei Haiyan , Tilakezi Tuersun , Feng Wei , Yang Heyin , Yang Shujun
Published: July 2024

Background

Contrast-induced acute kidney injury (CI-AKI) is a serious and common complication following the use of iodinated contrast media, with a 20% fatality rate. The function of long non-coding RNA HILPDA (lnc-HILPDA) in CI-AKI development was investigated in this study.

Methods

CI-AKI models were constructed by iopromide treatment. Kidney pathological changes were analyzed by HE staining. TUNEL labeling and flow cytometry were used to examine cell apoptosis. CCK-8 assay was used to determine cell viability. The interactions between lnc-HILPDA, eIF4B, and XPO1 were verified by RIP or Co-IP assay.

Results

Lnc-HILPDA was upregulated in CI-AKI, and its knockdown decreased contrast-trigged oxidative stress and apoptosis in HK-2 cells. Mechanically, lnc-HILPDA activated the NF-κB pathway by upregulating XPO1 through interacting with eIF4B. Moreover, the inhibitory effect of lnc-HILPDA downregulation on contrast-induced oxidative stress and apoptosis in HK-2 cells was weakened by XPO1 overexpression.

Conclusion

Lnc-HILPDA accelerated CI-AKI progression by elevating XPO1 expression through eIF4B to activate NF-κB pathway.
Return to Work After Surgery for Lumbar Disk Herniation
Authors: Hara Sozaburo , Aasdahl Lene , Salvesen Øyvind , Solberg Tore , Gulati Sasha , Hara Karen Walseth
Published: July 2024

Study Design.

An observational registry-based study.

Objective.

We investigated the long-term patterns of sick leave among patients undergoing surgery for lumbar disk herniation using two nationwide databases to study the achievement of post-surgery return to work (RTW).

Summary of Background Data.

The ability to RTW is increasingly recognized as an essential outcome measure for spine surgery.

Methods.

The study included 13,698 patients aged 18 to 60 on sick leave undergoing surgery for lumbar disk herniation from January 2007 through January 2019. Data from the Norwegian Registry for Spine Surgery (NORspine) and the Norwegian Labour and Welfare Administration (NAV) were linked. Certified sick leave around the time of surgery was assessed. The patients were further categorized according to the length of pre-surgery sick leave, and the rate of sustainable RTW for the different groups was compared using survival analysis. The association between successful surgical outcomes, defined by a 30% improvement in Oswestry Disability Index score, and achievement of sustainable RTW was analyzed using a logistic regression model.

Results.

Two years after surgery, 76% of the patients had returned to work. Shorter pre-surgery sick leave was associated with a higher proportion and rate of achieved sustainable RTW: Among patients with sick leave of less than 30 days, a total of 99% achieved sustainable RTW (median 46 d); only 40% of patients with longer-lasting work assessment allowance achieved the same goal within two years. Successful surgical outcomes were associated with sustainable RTW for all patient groups, but the impact of surgical success on RTW declined as sick leave extended beyond 180 days.

Conclusion.

Most patients had returned to work two years after lumbar disk herniation surgery. Shorter pre-surgery sick leave was associated with achieving faster and more sustainable RTW. Successful surgical outcomes had less impact on patients with extended sick leave.

Level of Evidence

III
Optimizing Cefiderocol Dosing Through Population Pharmacokinetic/Pharmacodynamic Simulation: An Assessment of Drug Cost Reductions
Authors: Oda Kazutaka , Jono Hirofumi , Saito Hideyuki
Published: July 2024

Background:

Cefiderocol is a siderophore cephalosporin antibiotic with bactericidal activity against carbapenem-resistant Enterobacterales. However, an efficient dosing strategy is yet to be developed. This study aimed to evaluate efficient lower-dose regimens and estimate potential drug cost reductions.

Methods:

This simulation study used a virtual population of 10,000 resampled individuals based on a reported population pharmacokinetic model. The target index for maximal bactericidal activity was the time for the unbound cefiderocol concentration to be above the minimum inhibitory concentration (TAM_unbound) of 100%, which was determined using a minimum inhibitory concentration distribution or specific value.

Results:

The probability of achieving 100% TAM_unbound with the standard, low- (reduced by 1 g or one dose), and extended low- (reduced by 2 g or 2 doses) dose regimens was nearly 100%. The lowest probability of achieving 100% TAM_unbound with the extended low-dose regimen at a creatinine clearance range of 90–120 mL/min was 86.4%. The probability of achieving TAM_unbound of 100% was more than 90% for MIC of ≤0.5 mcg/mL with the extended low-dosing regimen. Furthermore, using an efficient dosing regimen reduced the medical costs over a 10-day treatment period for 10 patients, from $122,826.50 to $62,665.69 $ and ¥12,598,187 $ to ¥5,451,173 in the United States and Japan, respectively.

ConclusionsS

A lower dosing regimen for cefiderocol could result in substantial reductions in drug costs while still achieving 100% TAM_unbound.
Relationship between the extraction methods, structural characteristics, and biological activities of polysaccharides from 5 typical polyporaceae fungi
Authors: Xu Xiajing , Wei Lihong , Zhang Yu , Cao Liqi , Hu Xiya , Liu Xiaoqiu , Pan Yingni
Published: July 2024

Polyporaceae fungi are widely found in nature and have long been an important part of the field of traditional Chinese medicine field. The numerous health benefits of Polyporaceae fungi may be related to their polysaccharides, which have significant biological activities in terms of antitumor, immunomodulation, antioxidation, liver protection, and blood lipid-lowering effects. Studies have shown that different extraction methods have a significant impact on the structural characteristics and biological activity of polysaccharides. The structural characteristics of fungal polysaccharides, such as composition, molecular weight, branching degree, and glycosidic bond type, are closely related to their biological activity. This article has systematically reviewed the relationship between the extraction and purification methods, structural characteristics, and biological activities of 5 typical fungal polysaccharides, aiming to provide a scientific basis for the application of polypore fungal polysaccharides in the field of traditional Chinese medicine and lay the foundation for their further research and development.
A Technique of Multiple Corneal Allogeneic Ring Segments Prepared From a Single Corneal Graft: A Case Series
Authors: Mechleb Nicole , Gatinel Damien , Saad Alain
Published: July 2024

Purpose:

To describe a novel technique for preparing multiple corneal allogeneic ring segments (CAIRS) from a single corneal graft using femtosecond laser technology.

Methods:

This is a case series of 10 eyes from 10 patients with keratoconus who underwent FS-assisted CAIRS implantation using corneas from 4 donors at the Hospital Foundation Adolphe de Rothschild-Noémie de Rothschild institute. A preoperative and postoperative examination was performed at 1 day, 1 week, and 1 month. Anterior segment OCT and corneal tomography with aberrometric and pachymetric analyses were performed at each visit. Visual, refractive, and topographic parameters were extracted. The thickness and width of implanted CAIRS were analyzed.

Results:

Patients were classified according to keratoconus severity: group A (maximal keratometry Kmax <75D) and group B (Kmax >75D). At 1 month postoperatively, both groups A and B showed a significant decrease in mean keratometry by 4.78 ± 1.57D and 12.87 ± 4.62D, respectively. Total and higher order aberrations decreased by 5.66 ± 4.55 and 0.65 ± 1.54 in group A and by 9.45 ± 9.15 and 0.49 ± 1.39 in group B, respectively. The corrected distance visual acuity improved by 4.8 ± 1.7 lines in group A. Visual improvement was not significant in group B. One eye in group B exhibited acute rejection and required explantation.

Conclusions:

FS-assisted multiple CAIRS implantation using a single corneal graft maximizes the utilization of viable corneal tissue. CAIRS implantation is an effective and biocompatible therapeutic alternative, particularly in cases of moderate to advanced keratoconus with Kmax <75D.
Risk Factors for Acute-Level Hospital Course in Pediatric Craniofacial Fractures
Authors: Perez-Otero Sofia , Cassidy Michael F. , Morrison Kerry A. , Brydges Hilliard T. , Tran David , Muller John , Flores Roberto L. , Ceradini Daniel J.
Published: July 2024

Purpose:

The pediatric craniofacial trauma literature is limited to single institutions or short study periods. Herein, this study analyzes a national database over 10 years to delineate the epidemiology of pediatric craniofacial fractures and to identify risk factors for acute-level hospital course in the largest series to date.

Methods:

Utilizing the National Trauma Data Bank, pediatric craniofacial fractures admitted between 2010 and 2019 were identified. Descriptive analyses and multivariable regression were performed to identify risk factors for acute-level hospital course.

Results:

A total of 155,136 pediatric craniofacial fracture cases were reviewed, including cranial vault (49.0%), nasal (22.4%), midface (21.0%), mandibular (20.2%), and orbital floor fractures (13.7%). Midface and orbital floor fractures occurred commonly as multicraniofacial fractures. Cranial vault fractures were the most common among all age groups, but frequency declined with age. In contrast, facial fractures increased with age. Despite the inherent complexity of multicraniofacial trauma, isolated fractures remained a concern for acute-level hospital course.

Cranial vault and midface fractures had an increased risk of intracranial injury and intensive care unit admission (P<0.001). Mandibular and midface fractures had an increased risk for cervical spine fracture and tracheostomy (P<0.001). Patient and injury-specific risk factors among the fractures with the strongest association for each outcome-cranial vault and mandible-were identified.

Conclusions:

The inherent limitations of prior studies—geographical biases, small cohorts, and short-term study periods—were addressed. Describing the independent contribution of each craniofacial fracture to the risk of acute-level hospital course outcomes can be employed to better optimize risk stratification, counseling, and management.
Dynamic Transcriptome Analysis of SFRP Family in Guided Bone Regeneration With Occlusive Periosteum in Swine Model
Authors: Chen Xiaoxue , Yu Baofu , Wang Zi , Zhou Qimin , Wu Qifeng , He Jinguang , Dai Chuanchang , Li Qingfeng , Wei Jiao
Published: July 2024

Background:

A variety of congenital or acquired conditions can cause craniomaxillofacial bone defects, resulting in a heavy financial burden and psychological stress. Guided bone self-generation with periosteum-preserved has great potential for reconstructing large bone defects.

Methods:

A swine model of guided bone regeneration with occlusive periosteum was established, the rib segment was removed, and the periosteum was sutured to form a closed regeneration chamber. Hematoxylin and eosin staining, Masson’s staining, and Safranine O-Fast Green staining were done. Nine-time points were chosen for collecting the periosteum and regenerated bone tissue for gene sequencing. The expression level of each secreted frizzled-related protein (SFRP) member and the correlations among them were analyzed.

Results:

The process of bone regeneration is almost complete 1 month after surgery, and up to 1 week after surgery is an important interval for initiating the process. The expression of each SFRP family member fluctuated greatly. The highest expression level of all members ranged from 3 days to 3 months after surgery. The expression level of SFRP2 was the highest, and the difference between 2 groups was the largest. Secreted frizzled-related protein 2 and SFRP4 showed a notable positive correlation between the control and model groups. Secreted frizzled-related protein 1, SFRP2, and SFRP4 had a significant spike in fold change at 1 month postoperatively. Secreted frizzled-related protein 1 and SFRP2 had the strongest correlation.

Conclusions:

This study revealed the dynamic expression of the SFRP family in guided bone regeneration with occlusive periosteum in a swine model, providing a possibility to advance the clinical application of bone defect repair.
Repeated stimulation of feeding mechanoafferents inAplysiagenerates responses consistent with the release of food
Authors: Hurwitz Itay , Tam Shlomit , Jing Jian , Chiel Hillel J. , Susswein Abraham J.
Published: July 2024

How does repeated stimulation of mechanoafferents affect feeding motor neurons? Monosynaptic connections from a mechanoafferent population in theAplysiabuccal ganglia to five motor followers with different functions were examined during repeated stimulus trains. The mechanoafferents produced both fast and slow synaptic outputs, which could be excitatory or inhibitory. In contrast, otherAplysiamechanoafferents produce only fast excitation on their followers. In addition, patterns of synaptic connections were different to the different motor followers. Some followers received both fast excitation and fast inhibition, whereas others received exclusively fast excitation. All followers showed strong decreases in fast postsynaptic potential (PSP) amplitude within a stimulus train. Fast and slow synaptic connections were of net opposite signs in some followers but not in others. For one follower, synaptic contacts were not uniform from all subareas of the mechanoafferent cluster. Differences in properties of the buccal ganglia mechanoafferents and otherAplysiamechanoafferents may arise because the buccal ganglia neurons innervate the interior of the feeding apparatus, rather than an external surface, and connect to motor neurons for muscles with different motor functions. Fast connection patterns suggest that these synapses may be activated when food slips, biasing the musculature to release food. The largest slow inhibitory synaptic PSPs may contribute to a delay in the onset of the next behavior. Additional functions are also possible.
Nonlinear electrodynamics for the vacuum of Dirac materials: Photon magnetic properties and radiation pressures
Authors: Jorge A. W. Romero , Martínez A. Pérez , Querts E. Rodríguez
Published: July 2024

We investigate the magnetic properties of photons propagating through Dirac materials in a magnetic field, considering both vacuum and medium contributions. Photon propagation properties are obtained through a second-order expansion of nonlinear Euler-Heisenberg electrodynamics at finite density and temperature considering Dirac material parameters (Dirac fine structure constant, band gap, and Fermi velocity). Total magnetization (including electron and photon contributions) and photon-effective magnetic moment are computed. Observables such as photon energy density, radiation pressure, and Poynting vector are obtained by an average of components of the energy-momentum tensor. All quantities are expressed in terms of Lagrangian derivatives. Those related to the vacuum are valid for any value of the external magnetic field, and both the weak- and strong-field limits are recovered. We discuss some ideas of experiments that may contribute to testing in Dirac materials the phenomenology of the strong magnetic field in the quantum electrodynamic (QED) vacuum and how nonlinear corrections on the magnetization, radiation pressure, and birefringence are amplified up to 103 times QED corrections.

Published by the American Physical Society
2024