bluuebunny/crossref_metadata_2025 huggingface dataset:
Multilevel analysis identifying the factors associated with RSV detection in infants admitted for viral bronchiolitis in the era of the COVID‐19 pandemic
Authors: Villamil‐Osorio Milena , Moyano‐Ariza Luisa F. , Camacho‐Moreno Germán , Restrepo‐Gualteros Sonia M. , Sossa‐Briceño Monica P. , Rodriguez‐Martinez Carlos E.
Published: July 2023

Objectives

To identify factors independently associated with respiratory syncytial virus (RSV) detection in infants admitted for viral bronchiolitis during 3 consecutive years, before and during the COVID‐19 pandemic, in Bogota, Colombia, a middle‐income country with a subtropical highland climate.

Methods

An analytical cross‐sectional study was conducted before and during the COVID‐19 pandemic, including patients with a diagnosis of viral bronchiolitis admitted to all the hospitals of the city between January 2019 and November 2021. We evaluated a set of a priori‐selected predictor variables that included individual, healthcare system, meteorological, air pollutant, and COVID‐19 variables. Since the variables analyzed are hierarchical in nature, multilevel modeling was used to identify factors independently associated with detection of RSV as the causative agent of viral bronchiolitis.

Results

A total of 13,177 patients were included in the study. After controlling for potential confounders, it was found that age (odds ratio [OR] 0.86; 95% confidence interval [CI] 0.76–0.97), a third level of medical care institution (OR 3.05; 95% CI 1.61–5.76), temperature (OR 1.60; 95% CI 1.24–2.07), rainfall (OR 1.003, 95% CI 1.001, 1.005), NO2 (OR 0.97; 95% CI 0.95–0.99), CO (OR 0.99; 95% CI 0.99–0.99), and COVID‐19 pandemic period (OR 0.84, 95% CI 0.71–0.99) were independently associated with RSV detection in our sample of patients.

Conclusions

The identified factors associated with RSV detection provide additional scientific evidence that may be useful in the development of specific interventions aimed at ameliorating or preventing the impact of RSV in Bogota and probably other similar low‐ to middle‐income countries in high‐risk infants.
Treatment response to pulmonary exacerbation in primary ciliary dyskinesia
Authors: Gatt Dvir , Shaw Michelle , Waters Valerie , Kritzinger Fiona , Solomon Melinda , Dell Sharon , Ratjen Felix
Published: July 2023

Introduction

Pulmonary exacerbation (Pex) are common in pediatric primary ciliary dyskinesia (PCD), however changes in forced expiratory volume in 1 s precent predicted (FEV1pp) during Pex are not well described.

Aim

To assess the evolution of FEV1pp during Pex and to define factors associated with failure to return to baseline lung function.

Method

This was a retrospective study of patients with PCD between 2010 and 2022. Pex were defined as the presence of increased respiratory symptoms treated with intravenous (IV) antibiotics. The main outcomes were the changes in FEV1 during therapy and the proportion of patients (responders) achieving ≥90% of baseline FEV1pp values at the end of admission.

Results

The study included 52 Pex events in 28 children with PCD. The rate of responders was 32/41 (78%) at the end of admission. Nonresponse was associated with lower median body mass index (BMI) Z‐score (−2.4 vs. −0.4, p < .01) and with a history of IV treated Pex in the previous year (p = .06). For the 22 Pex with available FEV1pp measurements at mid admission, the median relative and absolute improvement from admission to Day 7 was 9.1% and 6.2%, respectively (p‐ .001), and from Days 7 to 14 was 4.4% and 2.8%, respectively (p = .08).

Conclusion

In children with PCD treated with IV antibiotics, the majority of lung function recovery happens during the first week of IV therapy. Lower BMI was associated with nonresponse to therapy.
Actinomycins produced by endophyte Streptomyces sp. GLL‐9 from navel orange plant exhibit high antimicrobial effect against Xanthomonas citri susp. citri and Penicillium italicum
Authors: Gao Liangliang , Kumaravel Kaliaperumal , Xiong Qin , Liang Yan , Ju Zhiran , Jiang Yueming , Zhang Jun
Published: July 2023

BACKGROUND

Citrus canker and citrus blue mold are two severe diseases in citrus plants, which are mainly caused by Xanthomonas citri susp. citri (Xcc) and Penicillium italicum, respectively. The currently widely used pesticides for these two diseases are harmful to human health and the environment. Therefore, searching for novel antimicrobial agents, especially from natural resources, is getting increasing interest.

RESULTS

In this study, the crude extract of Streptomyces sp. GLL‐9, an endophyte from a navel orange tree, was found to exhibit excellent antimicrobial effects against Xcc and P. italicum. Bioassay‐guided isolation led to the discovery of three actinomycins (Acts), actinomycin X2 (Act‐X2), actinomycin D (ActD), and actinomycin XOβ (Act‐XOβ). The MIC (minimum inhibitory concentration) values of Act‐X2, ActD, and Act‐XOβ were 31.25, 62.50, and 62.50 μg mL−1 against Xcc, respectively, while 62.50 (Act‐X2) and 125.00 μg mL−1 (ActD) against P. italicum, being better or comparable to the positive controls. The highest yield of Acts was obtained by solid‐state fermentation with rice containing 1% L‐tryptophan as a culture medium, being 6.03, 3.07, and 1.02 mg g−1, for Act‐X2, ActD, and Act‐XOβ, respectively. The ethyl acetate extract of Streptomyces sp. GLL‐9 cultivated under the optimal fermentation conditions (EAE‐1) can efficiently control these two citrus diseases by excessively producing reactive oxygen species (ROS) in both pathogens, damaging the cell membranes of P. italicum, and inhibiting the growth of Xcc. In addition, Act‐X2, ActD, and EAE‐1 displayed broad‐spectrum antifungal activity.

CONCLUSION

EAE‐1 and Acts produced by Streptomyces sp. GLL‐9 have high potential as novel antimicrobial agents against plant pathogens. © 2023 Society of Chemical Industry.
Plant phylogeny determines host selection and acceptance of the oligophagous leaf beetle Cassida rubiginosa
Authors: Hettiarachchi Dilani K. , Rostás Michael , Sullivan Jon J. , Jackman Sarah , van Koten Chikako , Cripps Michael G.
Published: July 2023

BACKGROUND

Predicting the host range of biocontrol agents is important for the safe and effective implementation of biocontrol of weeds. In this study, we examined the phylogenetic pattern of host selection and acceptance by the biocontrol beetle, Cassida rubiginosa. The beetle was released in New Zealand for control of Cirsium arvense, its primary host plant, but has potential to attack many Cardueae (thistles and knapweeds) species. We conducted a series of no‐choice and choice experiments and modelled the responses of Cassida rubiginosa in relation to phylogenetic distance from Cirsium arvense.

RESULTS

The olfactory recognition (single odour) and preference (two odours) of the beetle showed a significant phylogenetic relationship. These relationships showed a high degree of correlation with 66.9% of the variation in olfactory recognition and 82.8% of the variation in olfactory preference explained by phylogeny. Where the beetle could contact plants, under no‐choice conditions there was no phylogenetic pattern to host plant acceptance. However, under choice conditions, phylogenetic distance was a strong predictor of feeding and oviposition preference. These relationships showed a high degree of correlation, with 63.4% of the variation in feeding preference, and 89.0% of the variation in oviposition preference, explained by phylogeny.

CONCLUSIONS

As far as we are aware, this is the first demonstration of an herbivorous insect that exhibits a phylogenetic pattern to olfactory host plant selection. Host plant utilisation by Cassida rubiginosa in New Zealand will be mostly restricted to Cirsium and Carduus species, with minimal potential for impact on other Cardueae weeds. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Enterolactone and trabectedin suppress epithelial ovarian cancer synergistically via upregulating THBS1
Authors: Zeng Zheng , Lin Caiji , Zhang Meng‐Chun , Kossinna Pathum , Wang Pengfei , Cao Danli , Wang Jiaxing , Xu Mengzhi , Wang Xiaoyu , Li Qing , Xu Xiaohui , Yang Hao , Zhu Songling , Liu Gui‐Rong , Xie Kaihong , Yang Jiaming , Luo Yao , Wang Yao , Zhang Xing‐Hua , Lin Jingwen , Chen Hang , Liu Shu‐Lin , Liu Huidi
Published: July 2023

Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown. To test combined suppressive effects of ENL and Trabe on EOC and possible involvement of THBS1 in the anticancer activities of ENL and Trabe. The EOC cell line ES‐2 was transfected with overexpressed THBS1 by lentivirus vector. We employed tube formation assay to evaluate the anti‐angiogenesis activity of ENL and of its combined use with Trabe after THBS1 overexpression and established drug intervention and xenograft nude mouse cancer models to assess the in vivo effects of the hypothesized synergistic suppression between the agents and the involvement of THBS1. Mouse fecal samples were collected for 16S rDNA sequencing and microbiota analysis. We detected strong inhibitory activities of ENL and Trabe against the proliferation and migration of cancer cells and observed synergistic effects between ENL and Trabe in suppressing EOC. ENL and Trabe, given either separately or in combination, could suppress the tube formation capability of human microvascular endothelial cells, and this inhibitory effect became even stronger with THBS1 overexpression. In the ENL plus Trabe combination group, the expression of tissue inhibitor of metalloproteinases 3 and cluster of differentiation 36 was both upregulated, whereas matrix metalloproteinase 9, vascular endothelial growth factor, and cluster of differentiation 47 were all decreased. With the overexpression of THBS1, the results became even more pronounced. In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti‐cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.
Paeoniflorin suppresses neuronal ferroptosis to improve the cognitive behaviors in Alzheimer's disease mice
Authors: Zhai Liping , Pei Hongyan , Shen Heping , Yang Yi , Han Chenyang , Guan Qiaobing
Published: July 2023

Aim of this research was to examine the impact of paeoniflorin (Pae) in suppressing the occurrence of ferroptosis in individuals with Alzheimer's disease (AD). The study utilized APP/PS1 mice with AD as the experimental subjects. Following the administration of Pae, the cognitive behaviors of mice were evaluated and the key indexes of ferroptosis were measured, as well as levels of oxidative stress (OS). For in‐vitro experiments, Erastin was adopted for inducing the ferroptosis of PC12 cells, and the level of cell ferroptosis was detected after Pae treatment. Pae improved the cognitive ability of AD mice, reduced the level of ferroptosis, decreased the iron ion and MAD levels in brain tissues, and increased SOD expression. In PC12 cells, Pae suppressed the Erastin‐induced ferroptosis, mitigated oxidative damage, and reduced the level of ROS. Based on the findings from our research, it was observed that Pae exhibited a specific binding affinity to P53, leading to the suppression of ferroptosis. This mechanism ultimately resulted in the improvement of nerve injury in mice with AD.
Effect of dietary supplementation with Diuripres® on blood pressure, vascular health, and metabolic parameters in individuals with high‐normal blood pressure or stage I hypertension: The CONDOR randomized clinical study
Authors: Fogacci Federica , Degli Esposti Daniela , Di Micoli Antonio , Fiorini Giulia , Veronesi Maddalena , Borghi Claudio , Cicero Arrigo F. G.
Published: July 2023

Our aim was to evaluate if a nutritional intervention with a dietary supplement (Diuripres®) containing magnesium, standardized extract of orthosiphon, hawthorn, and hibiscus could positively affect blood pressure (BP), vascular health, and metabolic parameters in 60 individuals with high‐normal BP or stage I hypertension. Participants followed a low‐fat low‐sodium Mediterranean diet for 4 weeks before being randomly allocated to 8‐week treatment with two pills each day of either Diuripres® or placebo. Diuripres® significantly decreased systolic BP compared to placebo after 4 weeks (3.1 ± 0.8 mmHg; p < 0.05) and more consistently after 8 weeks (3.4 ± 0.9 mmHg; p < 0.05). At 8‐week follow‐up, after correction for multiple testing, dietary supplementation with Diuripres® was associated with significant improvements in diastolic BP (−3.1 ± 0.6 mmHg; p < 0.05), aortic BP (−4.3 ± 0.4 mmHg; p < 0.05), and high‐sensitivity C‐reactive protein (hs‐CRP; 0.04 ± 0.01 mg/dL; p < 0.05) in comparison with baseline. The reductions in diastolic BP (−‐3.8 ± 0.7 mmHg; p < 0.05), aortic BP (−5.2 ± 1.0 mmHg; p < 0.05), and hs‐CRP (−0.03 ± 0.01 mg/dL; p < 0.05) were also significant compared to placebo. Therefore, our study shows that dietary supplementation with Diuripres® may be useful in individuals with high‐normal BP or stage I hypertension.
Nanoscale Vector Magnetometry with a Fiber‐Coupled Diamond Probe
Authors: Liu Hang‐Yu , Liu Wen‐Zhao , Wang Meng‐Qi , Ye Xiang‐Yu , Yu Pei , Sun Hao‐Yu , Liu Zhi‐Xian , Liu Zhao‐Xin , Zhou Jing‐Wei , Wang Peng‐Fei , Shi Fa‐Zhan , Wang Ya
Published: July 2023

A nanoscale vector magnetometer is demonstrated by integrating a microfabricated diamond probe with a nanopillar on top of a single‐mode optical fiber. Based on the recently developed self‐aligned patterning techniques, ≈80 nitrogen vacancies are concentrated at a 100 nm2 area at the center of nanopillars to maximize the excitation and collection efficiencies. The spatial resolution of such a fiber‐coupled diamond magnetometer can reach 100 nm for the first time with a sensitivity of 11.27 µT/ for DC magnetic field sensing. In addition, the probe can provide deterministic oriented diamond nanopillars for simplified vector magnetometry. This fiber‐coupled diamond probe is applied to demonstrate the magnetic field imaging of charged electrodes in a confined box. These results mark a decisive step toward fiber‐based applications with nanoscale vector magnetometry capabilities.
A threat‐intelligence driven methodology to incorporate uncertainty in cyber risk analysis and enhance decision‐making
Authors: Dekker Martijn , Alevizos Lampis
Published: July 2023

The challenge of decision‐making under uncertainty in information security has become increasingly important, given the unpredictable probabilities and effects of events in the ever‐changing cyber threat landscape. Cyber threat intelligence provides decision‐makers with the necessary information and context to understand and anticipate potential threats, reducing uncertainty, and improving the accuracy of risk analysis. The latter is a principal element of evidence‐based decision‐making, and it is essential to recognize that addressing uncertainty requires a new, threat‐intelligence (TI) driven methodology, and risk analysis approach. We propose a solution to this challenge by introducing a TI‐based security assessment methodology and a decision‐making strategy that considers both known unknowns and unknown unknowns. The proposed methodology aims to enhance the quality of decision‐making by utilizing causal graphs, which offer an alternative to conventional methodologies that rely on attack trees, resulting in a reduction of uncertainty. Furthermore, we consider tactics, techniques, and procedures that are possible, probable, and plausible, improving the predictability of adversary behavior. Our proposed solution provides practical guidance for information security leaders to make informed decisions in uncertain situations. This paper offers a new perspective on addressing the challenge of decision‐making under uncertainty in information security by introducing a methodology that can help decision‐makers navigate the intricacies of the dynamic and continuously evolving landscape of cyber threats.
Monitoring and data‐informed approaches for the assessment of existing structures
Authors: Strauss Alfred , Bergmeister Konrad , Daró Paola , Mancini Giuseppe , Sattler Fabian , Bigaj‐van Vliet Agnieszka
Published: July 2023

Accurate information from monitoring of structures plays a critical role in making informed decisions regarding structural safety control and maintenance needs. Unfortunately, there are several gaps in the existing standards and the monitoring practices at local, national, and transnational (e.g., European) levels. The wide diversity of assets and their respective environments further complicates the development of standardized monitoring approaches. Despite the constantly increasing number of examples and intensive knowledge exchange on the use of information from inspection, testing, and monitoring to support the safety and risk assessment of existing structures, major challenges are being faced in establishing consensus on standardization in this domain. At the same time, the need for robust standardization that enables integrating structural monitoring with the assessment of existing structures is generally acknowledged by public authorities and industrial stakeholders. Extending the lifespan of structures to enhance sustainability is a critical imperative of our time and monitoring is expected to be key element of reliable service life extension of existing structures. However, development and adoption of new standards involve complex processes that require multi‐level dialogues, consensus, and commitment from political and industrial stakeholders to move forward from legacy procedures. The fib Model Code 2020 (MC2020) serves as a significant milestone in the development of new standards for monitoring and maintenance of concrete structures. It addresses the existing gaps in knowledge and seeks to close the gap between the practice and the standards with regard to the monitoring of structures. The important objectives of the MC2020 are to support the standardization bodies in formulating new standards in monitoring, maintenance, and safety of existing concrete structures. This paper presents the fundamental/basis for shaping the methodology of data‐driven assessment and the methodologies proposed in the ModelCode.
METTL3‐mediated m6A modification of pri‐miR‐148a‐3p affects prostate cancer progression by regulating TXNIP
Authors: Li Guoqiang , Liu Junwen , Wang Yinhuai , Liu Hanqi , Fu Jianhan , Zhao Yuanqiao , Huang Yanqing
Published: July 2023

Objective

Prostate cancer (PCa) severely affects men's health worldwide. The mechanism of methyltransferase‐like 3 (METTL3) in affecting PCa development by regulating miR‐148a‐3p expression via N6‐methyladenosine (m6A) modification was investigated.

Methods

METTL3, miR‐148a‐3p, and thioredoxin interacting protein (TXNIP) levels were determined using RT‐qPCR and Western blotting. The m6A modification level of miR‐148a‐3p was observed by Me‐RIP assay. Bioinformatics website predicted miR‐148a‐3p and TXNIP levels in PCa and their correlation, and the binding site between them was verified by dual‐luciferase assay. The proliferation, migration, invasion, and apoptosis of PCa cells were examined by CCK‐8 assay, Transwell assay, and flow cytometry. A transplanted tumor model was established in nude mice to observe the tumor growth ability, followed by determination of TXNIP levels in tumor tissues by immunohistochemistry.

Results

METTL3 interference restrained the proliferation, migration, and invasion and promoted apoptosis of PCa cells. METTL3 up‐regulated miR‐148a‐3p by promoting the m6A modification of pri‐miR‐148a‐3p in PCa cells. miR‐148a‐3p overexpression nullified the inhibitory actions of silencing METTL3 on PCa cell growth. miR‐148a‐3p facilitated PCa cell growth by silencing TXNIP. METTL3 interference inhibited tumor growth by down‐regulating miR‐148a‐3p and up‐regulating TXNIP.

Conclusion

METTL3 promoted miR‐148a‐3p by mediating the m6A modification of pri‐miR‐148a‐3p, thereby targeting TXNIP, interfering with METTL3 to inhibit the proliferation, migration and invasion of PCa cells, promote apoptosis, and inhibit tumor growth in nude mice.
RETRACTED: Transcriptomic landscape of endothelial cells: Key tumor microenvironment components indicating variable clinical outcomes in pancreatic ductal adenocarcinoma
Authors: Xie Peng , Tan Si‐Yuan , Li Hai‐Feng , Tang Hao‐Dong , Zhou Jia‐hua
Published: July 2023

Endothelial cells (ECs) present in the tumor microenvironment (TME) exhibit significant diversity that may impact the efficacy of anti‐tumor treatments. Thus, our study sought to elucidate the various clusters of ECs present in pancreatic ductal adenocarcinoma (PDAC) and explore their possible interactions and influence on clinical outcomes. We obtained single‐cell transcriptome data from 24 PDAC tumors and 11 normal pancreases, minimizing any batch effects between samples. Next, we compared the relative abundance of various ECs clusters across distinct sample types. Pseudo‐time analysis was employed to investigate the differentiation origin of ECs. A variety of bioinformatics methods were used to investigate potential communication between ECs and malignant cells, as well as assess metabolic changes, pathway alterations, and immune‐related markers expression within distinct EC clusters. Lastly, we investigated the impact of particular ECs clusters on patient prognosis in bulk transcriptome data. Our study identified seven distinct clusters of ECs, denoted as CA4+ ECs, MMP2+ ECs, SPP1+ ECs, MT1F+ ECs, CCL5+ ECs, RGS5+ ECs, and TYROBP+ ECs. Pseudo‐time analysis suggested that the loss of CA4+ ECs and MT1F+ ECs may promote malignant progression. Cell communication elucidated that MT1F+ ECs exhibited the strongest outgoing interaction strength, whereas RGS5+ ECs displayed the strongest incoming interaction strength. Furthermore, TYROBP+ ECs exhibited greater metabolic activity, and notably, CCL5+ ECs displayed increased expression of immune‐related molecules. Lastly, across cohorts of bulk transcriptome levels, CA4+ ECs, MT1F+ ECs, and RGS5+ ECs consistently demonstrated prognostic indicative effects. PDAC patients exhibit the presence of seven distinct EC clusters, each demonstrating significant metabolic and immunological heterogeneity. Targeted therapeutic approaches directed toward CA4+ ECs and MT1F+ ECs may prove advantageous in addressing challenges associated with PDAC treatment. Additionally, variations in the relative abundance of CA4+ ECs, MT1F+ ECs, and RGS5+ ECs were indicated as predictive of patient prognosis.
Circ_LRP6 facilitates osteosarcoma progression via the miR‐122‐5p/miR‐204‐5p/HMGB1 axis
Authors: Wang Guanghui , Wei Xiyuan , Gao Shan , Chen Wenheng , Geng Yang , Liu Jia , Guan Hongya
Published: July 2023

Circ_LRP6 is participated in the occurrence and development of numerous tumors. Nevertheless, its roles and mechanism in osteosarcoma (OS) is unknown. This study aims to illustrate this point. With the use of qRT‐PCR, the level of circ_LRP6, miR‐122‐5p, miR‐204‐5p and HMGB1 was identified. To observe cell proliferation, migration and invasion, we adopted CCK‐8 and Transwell assays in the present study. Besides, to prove the existing interaction, bioinformatics analysis and dual luciferase reporting assays were employed. The influence of circ_LRP6 on osteosarcoma in vivo was evaluated by subcutaneous tumor formation model in nude mice. In osteosarcoma tissues, circ_LRP6 and HMGB1 are strongly denoted, whereas miR‐122‐5p and miR‐204‐5p are under‐expressed. Circ_LRP6 knockdown could significantly hinder the proliferation, migration and invasion of osteosarcoma cells. Circ_LRP6 hindered the proliferation of osteosarcoma in vivo. Bioinformatics predicted that miR‐122‐5p and miR‐204‐5p functioned as direct targets of circ_LRP6, and HMGB1 were possible target genes of miR‐122‐5p and miR‐204‐5p. The findings indicated that the low level of miR‐122‐5p and miR‐204‐5p and the overexpression of HMGB1 could partially restore and reduce the inhibitory impact of circ_LRP6 on the proliferation, migration and invasion of osteosarcoma cells. Circ_LRP6 affects osteosarcoma progression via the miR‐122‐5p/miR‐204‐5p/HMGB1 axis, and is shown to be a molecular biomarker.
A new coupling of a GPU‐resident large‐eddy simulation code with a multiphysics wind turbine simulation tool
Authors: Taschner Emanuel , Folkersma Mikko , A Martínez‐Tossas Luis , Verzijlbergh Remco , van Wingerden Jan‐Willem
Published: July 2023

The development of new wind farm control strategies can benefit from combined analysis of flow dynamics in the farm and the behavior of individual turbines within one simulation environment. In this work, we present such an environment by developing a new coupling between the large‐eddy simulation (LES) code GRASP and the multiphysics wind turbine simulation tool OpenFAST via an actuator line model (ALM). In addition, the implementation of the recently proposed filtered actuator line model (FALM) within the coupling is described. The new ALM implementation is cross‐verified with results from four other commonly used research LES codes. The results for the blade loads and the near wake obtained with the new coupling are consistent with the other codes. Deviations are observed in the far wake. The results further indicate that the FALM is able to reduce the lift and power overprediction from which the traditional ALM suffers on coarse LES grids. This new simulation environment paves the way for future wind farm simulations under realistic weather conditions by leveraging GRASP's ability to impose data from large‐scale meteorological models as boundary conditions.
Dewey, Existential Uncertainty and Non-affirmative Democratic Education
Authors: English Andrea R.
Published: July 2023

In this chapter, I show how John Dewey’s understanding of the educational meaning of existential uncertainty lies at the heart of his idea of democratic education. Specifically, I argue that Dewey’s theory of democratic education is grounded in a concept of transformative learning that necessarily involves experiences of existential uncertainty, and, in a concept of teaching that necessarily involves supporting learners’ opportunities to have educative experiences of existential uncertainty. In doing so, I aim to bring this democratic aspect of Dewey’s notion of teaching into sharper relief by showing how it offers a productive extension of the tradition ofnon-affirmativeeducational theory. In section one, “Uncertainty and the beginning of learning”, I discuss the notion of existential uncertainty and its relation to what Dewey called “the indeterminate situation” as a realm of learning that we find ourselves inprior tosearching for and finding a problem, and thus logically prior to solving it. In section two, “Existential uncertainty, teaching and democratic education”, I discuss Dewey’s notion of teaching within the context of his broader theory of democratic education, highlighting it as a form of teaching that is non-affirmative, by contrasting it to “traditional, transmissive” and, what I call, “reductive-progressive” forms of teaching. In the final section, “Listening and Relationality”, I build on and move beyond Dewey to formulate a notion of theteacher as a listener. I argue that this understanding of the teacher is vitally relevant for the theory and practice of democratic education as non-affirmative education, and yet is in danger of being lost in the current measurement culture in education.
Keeping matter in the loop in dS3 quantum gravity
Authors: Castro Alejandra , Coman Ioana , Fliss Jackson R. , Zukowski Claire
Published: July 2023

Abstract

We propose a mechanism that couples matter fields to three-dimensional de Sitter quantum gravity. Our construction is based on the Chern-Simons formulation of three-dimensional Euclidean gravity, and it centers on a collection of Wilson loops winding around Euclidean de Sitter space. We coin this object a Wilson spool. To construct the spool, we build novel representations of 𝔰𝔲(2). To evaluate the spool, we adapt and exploit several known exact results in Chern-Simons theory. Our proposal correctly reproduces the one-loop determinant of a free massive scalar field on S3 as GN → 0. Moreover, allowing for quantum metric fluctuations, it can be systematically evaluated to any order in perturbation theory.
Ensemble averaging in JT gravity from entanglement in Matrix Quantum Mechanics
Authors: Di Ubaldo Gabriele , Policastro Giuseppe
Published: July 2023

Abstract

We consider the generalization of a matrix integral with arbitrary spectral curve ρ0(E) to a 0+1D theory of matrix quantum mechanics (MQM). Using recent techniques for 1D quantum systems at large-N, we formulate a hydrodynamical effective theory for the eigenvalues. The result is a simple 2D free boson BCFT on a curved background, describing the quantum fluctuations of the eigenvalues around ρ0(E), which is now the large-N limit of the quantum expectation value of the eigenvalue density operator $$ \hat{\rho}(E) $$

ρ
̂

E

.

The average over the ensemble of random matrices becomes a quantum expectation value. Equal-time density correlations reproduce the results (including non-perturbative corrections) of random matrix theory. This suggests an interpretation of JT gravity as dual to a one-time-point reduction of MQM.

As an application, we compute the Rényi entropy associated to a bipartition of the eigenvalues. We match a previous result by Hartnoll and Mazenc for the c = 1 matrix model dual to two-dimensional string theory and extend it to arbitrary ρ0(E). The hydrodynamical theory provides a clear picture of the emergence of spacetime in two dimensional string theory. The entropy is naturally finite and displays a large amount of short range entanglement, proportional to the microcanonical entropy. We also compute the reduced density matrix for a subset of n < N eigenvalues.
Moduli of relative stable maps to $$\mathbb {P}^1$$: cut-and-paste invariants
Authors: Kannan Siddarth
Published: July 2023

We study constructible invariants of the moduli space $$\hspace{0.83328pt}\overline{\hspace{-0.83328pt}\mathcal {M}\hspace{-0.83328pt}}\hspace{0.83328pt}(\varvec{x})$$

M

¯

(

x

)

of stable maps from genus zero curves to $$\mathbb {P}^1$$

P

1

, relative to 0 and $$\infty $$
∞
, with ramification profiles specified by $${\varvec{x}\in \mathbb {Z}^n}$$

x

∈

Z

n

. These spaces are central to the enumerative geometry of $$\mathbb {P}^1$$

P

1

, and provide a large family of birational models of the Deligne–Mumford–Knudsen moduli space $$\hspace{0.83328pt}\overline{\hspace{-0.83328pt}\mathcal {M}\hspace{-0.83328pt}}\hspace{0.83328pt}_{0,n}$$

M

¯

0
,
n

. For the sequence of vectors $$\varvec{x}$$

x

corresponding to maps which are maximally ramified over 0 and unramified over $$\infty $$
∞
, we prove that a generating function for the topological Euler characteristics of these spaces satisfies a differential equation which allows for its recursive calculation. We also show that the class $${[\hspace{0.83328pt}\overline{\hspace{-0.83328pt}\mathcal {M}\hspace{-0.83328pt}}\hspace{0.83328pt}(\varvec{x})] \in K_0(\textsf{Var}/\mathbb {C})}$$

[

M

¯

(

x

)

]

∈

K
0

(
Var
/
C
)

of the moduli space in the Grothendieck ring of varieties is constant as $$\varvec{x}$$

x

varies within a fixed chamber in the resonance decomposition of $$\mathbb {Z}^n$$

Z

n

. We conclude by suggesting several further directions in the study of these spaces, giving conjectures on (1) the asymptotic behavior of the Euler characteristic and (2) a potential chamber structure for the Chern numbers.
The evolving role of reduced-dose total skin electron beam therapy in skin malignancies: the renaissance of a rare indication
Authors: Elsayad Khaled , Eich Hans Theodor
Published: July 2023

Definitive radiation therapy is an effective local treatment for several cutaneous malignancies. Patients with diffuse or generalized skin manifestations might require total skin electron beam therapy (TSEBT) as an alternative treatment to the chasing technique. In this short communication, we highlight the evolving role of TSEBT and present its role in various forms of skin malignancies.
Genetics of diabetes-associated microvascular complications
Authors: Lyssenko Valeriya , Vaag Allan
Published: July 2023

Diabetes is associated with excess morbidity and mortality due to both micro- and macrovascular complications, as well as a range of non-classical comorbidities. Diabetes-associated microvascular complications are those considered most closely related to hyperglycaemia in a causal manner. However, some individuals with hyperglycaemia (even those with severe hyperglycaemia) do not develop microvascular diseases, which, together with evidence of co-occurrence of microvascular diseases in families, suggests a role for genetics. While genome-wide association studies (GWASs) produced firm evidence of multiple genetic variants underlying differential susceptibility to type 1 and type 2 diabetes, genetic determinants of microvascular complications are mostly suggestive. Identified susceptibility variants of diabetic kidney disease (DKD) in type 2 diabetes mirror variants underlying chronic kidney disease (CKD) in individuals without diabetes. As for retinopathy and neuropathy, reported risk variants currently lack large-scale replication. The reported associations between type 2 diabetes risk variants and microvascular complications may be explained by hyperglycaemia. More extensive phenotyping, along with adjustments for unmeasured confounding, including both early (fetal) and late-life (hyperglycaemia, hypertension, etc.) environmental factors, are urgently needed to understand the genetics of microvascular complications. Finally, genetic variants associated with reduced glycolysis, mitochondrial dysfunction and DNA damage and sustained cell regeneration may protect against microvascular complications, illustrating the utility of studies in individuals who have escaped these complications.

Graphical Abstract
Better post‐operative outcomes at 1‐year follow‐up are associated with lower levels of pre‐operative synovitis and higher levels of IL‐6 and VEGFA in unicompartmental knee arthroplasty patients
Authors: Tay Mei Lin , Bolam Scott M. , Monk A. Paul , McGlashan Sue R. , Young Simon W. , Matthews Brya G.
Published: July 2023

Purpose

Osteoarthritis (OA) is associated with inflammation, and residual inflammation may influence outcomes following knee arthroplasty. This may be more relevant for patients undergoing unicompartmental knee arthroplasty (UKA) due to larger remaining areas of native tissue. This study aimed to: (1) characterise inflammatory profiles for medial UKA patients and (2) investigate whether inflammation markers are associated with post‐operative outcomes.

Methods

This prospective, observational study has national ethics approval. Bloods, synovial fluid, tibial plateaus and synovium were collected from medial UKA patients in between 1 January 2021 and 31 December 2021. Cytokine and chemokine concentrations in serum and synovial fluid (SF) were measured with multiplexed assays. Disease severity of cartilage and synovium was assessed using validated histological scores. Post‐operative outcomes were measured with Oxford Knee Score (OKS), Forgotten Joint Score (FJS‐12) and pain scores.

Results

The study included 35 patients. SF VEGFA was negatively correlated with pre‐operative pain at rest (r − 0.5, p = 0.007), and FJS‐12 at six‐week (r 0.44, p = 0.02), six‐month (r 0.61, p < 0.01) and one‐year follow‐up (r 0.63, p = 0.03). Serum and SF IL‐6 were positively correlated with OKS at early follow‐up (serum 6 weeks, r 0.39, p = 0.03; 6 months, r 0.48, p < 0.01; SF 6 weeks, r 0.35, p = 0.04). At six weeks, increased synovitis was negatively correlated with improvements in pain at rest (r − 0.41,p = 0.03) and with mobilisation (r − 0.37, p = 0.047).

Conclusion

Lower levels of synovitis and higher levels of IL‐6 and VEGFA were associated with better post‐operative outcomes after UKA, which could be helpful for identifying UKA patients in clinical practice.

Level of evidence

Level IV case series.
Low early complication rates after arthroscopic meniscus repair and meniscectomy
Authors: Lai Wilson C. , Mange Tyler R. , Karasavvidis Theofilos , Lee Yu‐Po , Wang Dean
Published: July 2023

Purpose

To evaluate the 30‐day complication rates after arthroscopic meniscus repair and meniscectomy using the American College of Surgeons National Surgical Quality Improvement Program (ACS‐NSQIP) database, with subgroup analysis of patients aged > 40 years.

Methods

NSQIP registries between 2006 and 2019 were queried using Current Procedural Terminology codes to identify patients undergoing arthroscopic meniscus repair (CPT 29882, 29883) and meniscectomy (29880, 29881). The following 30‐day complications were assessed: pulmonary embolism (PE), venous thromboembolism (VTE), surgical site infection (SSI), reoperation, and readmission. Complications rates between treatment groups were compared using multivariate logistic regression analyses adjusted for sex, age, steroid use, and smoking/dyspnoea/COPD. A subgroup analysis was performed for patients aged > 40 years.

Results

A total 6354 meniscus repairs and 99,372 meniscectomies were identified. Complication rates were < 1% for both meniscus repair and meniscectomy. Meniscus repair was associated with significantly higher rates of PE, VTE, and readmission compared to meniscectomy: PE (0.2% vs 0.1%, p < 0.001), VTE (0.8% vs 0.4%, p < 0.001), superficial SSI (0.1% vs 0.2%, n.s), deep SSI (0.07% vs 0.1%, n.s), reoperation (0.5% vs 0.4%, n.s), and readmission (0.9% vs 0.8%, p = 0.003). Among patients aged > 40 years, complication rates were < 1.3% for both meniscus repair and meniscectomy. Similar trends and rates were found in patients aged > 40 years undergoing meniscus repair versus meniscectomy: PE (0.38% vs 0.12%, p < 0.001), VTE (1.07% vs 0.46%, p < 0.001), superficial SSI (0.03% vs 0.19%, n.s), deep SSI (0.1% vs 0.06%, n.s), reoperation (0.48% vs 0.43%, n.s), and readmission (1.2% vs 0.85%, p = 0.01).

Conclusion

Arthroscopic meniscus repair and meniscectomy are both low‐risk procedures with 30‐day complication rates < 1% overall and < 1.3% among patients aged > 40 years. These findings support meniscus repair whenever feasible in the setting of preserved articular cartilage. Understanding of the short‐term complication rates after arthroscopic meniscus repair and meniscectomy can aid surgeons in providing comprehensive preoperative counselling to patients considering such treatments, specifically when discussing the risks and benefits of meniscus repair.

Level of evidence

III.
Mechanistic aspects of ameliorative effects of Eicosapentanoic acid ethyl ester on methotrexate-evoked testiculopathy in rats
Authors: Abbas Noha A. T. , El-Sayed Shaimaa S. , Abd El-Fatah Samaa Salah , Sarhan Walaa M. , Abdelghany Eman M. A. , Sarhan Omnia , Mahmoud Shireen S.
Published: July 2023

Disrupted spermatogenesis and testicular injury are among the devastating outcomes of methotrexate. A major contributor to methotrexate-induced testiculopathy is oxidative damage which triggers apoptosis and altered autophagy responses. Eicosapentaenoic acid ethyl ester (EPA-E) is an antihyperlipidemic derivative of omega-3 fatty acids that exhibited affinity to peroxisome proliferator-activated receptor-γ (PPAR-γ) that possesses both antioxidant and autophagy modulating properties. This is an exploratory study aiming at assessing the effectiveness of EPA-E to alleviate testicular damage induced by methotrexate. The specific exploratory hypothesis of this experiment is: EPA-E administration for 1 week to methotrexate-treated rats reduces testicular damage compared to control rats. As a secondary outcome, we were interested in identifying the implicated mechanism that mediates the action of EPA-E. In adult male Wistar rats, testiculopathy was achieved by a single methotrexate injection (20 mg/kg, ip). Rats received vehicle, EPA-E (0.3 g/kg/day, po) alone or with selective PPAR-γ antagonist (bisphenol A diglycidyl ether, BADGE) at 30 mg/kg/day, ip for 1 week. EPA-E recuperated methotrexate-attenuated serum total testosterone while reduced testicular inflammation and oxidative stress, restoring superoxide dismutase (SOD) while reducing malondialdehyde (MDA) and 8–hydroxy–2′-deoxyguanosine (8-OHdG). Methotrexate-induced testicular apoptosis (caspase-3 and p53) was suppressed upon EPA-E treatment. Besides, EPA-E curbed methotrexate-induced abnormal autophagy by downregulating LC3A/B and beclin-1. Interestingly, BADGE-coadministration reversed EPA-E beneficial actions. Collectively, our findings suggest PPAR-γ role in EPA-E-mediated mitigation of methotrexate-evoked testiculopathy via suppression of oxidative stress, apoptosis, as well as abnormal autophagy. Furthermore, EPA-E could be used as a preventive therapy for some testiculopathies mediated by oxidative stress.

Graphical Abstract
Retrograde amnesia abolishes the self-reference effect in anterograde memory
Authors: Stendardi Debora , De Luca Flavia , Gambino Silvia , Ciaramelli Elisa
Published: July 2023

Is retrograde amnesia associated with an ability to know who we are and imagine what we will be like in the future? To answer this question, we had S.G., a patient with focal retrograde amnesia following hypoxia, two brain-damaged (control) patients with no retrograde memory deficits, and healthy controls judge whether each of a series of trait adjectives was descriptive of their present self, future self, another person, and that person in the future, and later recognize studied traits among distractors. Healthy controls and control patients were more accurate in recognizing self-related compared to other-related traits, a phenomenon known as the self-reference effect (SRE). This held for both present and future self-views. By contrast, no evidence of (present or future) SRE was observed in SG, who concomitantly showed reduced certainty about his personality traits. These findings indicate that retrograde amnesia can weaken the self-schema and preclude its instantiation during self-related processing.
The Impact of Obesity on the Resolution of Hypertension Following Adrenalectomy for Primary Hyperaldosteronism
Authors: Chidambaram Swathikan , Van Den Heede Klaas , Damji Samir , Meeran Karim , Todd Jeannie , Wernig Florian , Palazzo Fausto , Di Marco Aimee N.
Published: July 2023

Background

This study aims to determine the impact of patient obesity on the resolution of hypertension and pill burden post‐adrenalectomy for PA. Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension that may be remedied with surgery (unilateral adrenalectomy). Obesity may independently cause hypertension through several mechanisms including activation of the renin–angiotensin–aldosterone pathway. The influence of obesity on the efficacy of adrenalectomy in PA has not been established.

Methods

This is a retrospective analysis of prospectively collected data on patients undergoing adrenalectomy for PA at a single, tertiary‐care surgical centre from January 2015 to December 2020. Electronic health records of patients were screened to collect relevant data. The primary outcomes of the study include post‐operative blood pressure, the reduction in the number of anti‐hypertensive medications and potassium supplementation burden post‐adrenalectomy.

Results

Fifty‐three patients were included in the final analysis. There was a significant reduction in the blood pressure and the number of anti‐hypertensive medications in all patients after adrenalectomy (p < 0.001). Of the 34 patients (64.2%) with pre‐operative hypokalaemia, all became normokalaemic and were able to stop supplementation. However obese patients required more anti‐hypertensive medications to achieve an acceptable blood pressure than overweight or normal BMI patients (p < 0.01). Multivariate logistic regression analysis showed that male gender and BMI were independent predictors of resolution of hypertension (p <0.01).

Conclusion

Unilateral adrenalectomy improves the management of hypertension and hypokalaemia when present in patients with PA. However, obesity has an independent deleterious impact on improvement in blood pressure post‐adrenalectomy for PA.
Standardised Competency‐Based Training of Medical Doctors and Associate Clinicians in Inguinal Repair with Mesh in Sierra Leone
Authors: Ashley Thomas , Ashley Hannah F. , Wladis Andreas , Nordin Pär , Ohene‐Yeboah Michael , Rukas Rimantas , Lipnickas Vytautas , Smalle Isaac O. , Holm Kristina , Kalsi Herta , Palmu Juuli , Sahr Foday , Beard Jessica H. , Löfgren Jenny , Bolkan Håkon A. , van Duinen Alex J.
Published: July 2023

Introduction

In low‐income settings, there is a high unmet need for hernia surgery, and most procedures are performed with tissue repair techniques. In preparation for a randomized clinical trial, medical doctors and associate clinicians received a short‐course competency‐based training on inguinal hernia repair with mesh under local anaesthesia. The aim of this study was to evaluate feasibility, safety and effectiveness of the training.

Methods

All trainees received a one‐day theoretical module on mesh hernia repair under local anaesthesia followed by hands‐on training. Performance was assessed using the American College of Surgeon’s Groin Hernia Operative Performance Rating System. Patients were followed up two weeks and one year after surgery. Outcomes of the patients operated on during the training trial were compared to the 229 trial patients operated on after the training.

Results

During three surgical camps, seven medical doctors and six associate clinicians were trained. In total, 129 patients were operated on as part of the training. Of the 13 trainees, 11 reached proficiency. Patients in the training group had more wound infections after two weeks (8.5% versus 3.1%; p = 0.041). There was no difference in recurrence and mortality after one year, and none of the deaths were attributed to the surgery.

Discussion and conclusion

Mesh repair is the international standard for inguinal hernia repair worldwide. Nevertheless, this is not widely accessible in low‐income settings. This study has demonstrated that short‐course intensive hands‐on training of MDs and ACs in mesh hernia repair is effective and safe.

Trial Registration: International Clinical Trial Registry ISRCTN63478884.