bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency and burden of disease for SARS‐CoV‐2 and other viral respiratory tract infections in children under the age of 2 months
Authors: Latouche Marie , Ouafi Mahdi , Engelmann Ilka , Becquart Adrien , Alidjinou Enagnon Kazali , Mitha Ayoub , Dubos François
Published: October 2023

Objective

To evaluate the frequency and burden of disease of SARS‐CoV‐2 and other respiratory viruses in children under the age of 2 months.

Methods

A retrospective, cross‐sectional, single‐center study was conducted between March 2021 and February 2022. All children under the age of 2 months and tested for SARS‐CoV‐2 were included. The frequency of SARS‐CoV‐2, of other respiratory viruses and the burden of disease caused by SARS‐CoV‐2 and other respiratory viruses were evaluated.

Results

Seven hundred and twenty‐seven children with an RT‐PCR test for SARS‐CoV‐2 were included (mean age: 0.9 months (±0.6); boys: 57%); 514 (71%) in the emergency room and 213 (29%) in hospital. Among them, 62 (8.5%) had a positive RT‐PCR test for SARS‐CoV‐2, more often in the Omicron period (23%) than in the Alpha period (4%). Of the 565 (78%) with a multiplex RT‐PCR test for other viruses, 325 (58%) were positive. Children with a positive SARS‐CoV‐2 were less likely to have required respiratory support (p = 0.001), enteral nutrition (p = 0.03), or intensive care admission (p = 0.01) and had a shorter hospital stay than children with other respiratory viruses (5 days vs. 7 days, p = 0.007).

Conclusion

In this young population of children, SARS‐CoV‐2 infection was less frequent and less severe than other viral respiratory infections.
Applied physiologically‐based pharmacokinetic modeling to assess uridine diphosphate‐glucuronosyltransferase‐mediated drug–drug interactions for Vericiguat
Authors: Frechen Sebastian , Ince Ibrahim , Dallmann André , Gerisch Michael , Jungmann Natalia A. , Becker Corina , Lobmeyer Maximilian , Trujillo Maria E. , Xu Shiyao , Burghaus Rolf , Meyer Michaela
Published: October 2023

Vericiguat (Verquvo; US: Merck, other countries: Bayer) is a novel drug for the treatment of chronic heart failure. Preclinical studies have demonstrated that the primary route of metabolism for vericiguat is glucuronidation, mainly catalyzed by uridine diphosphate‐glucuronosyltransferase (UGT)1A9 and to a lesser extent UGT1A1. Whereas a drug–drug interaction (DDI) study of the UGT1A9 inhibitor mefenamic acid showed a 20% exposure increase, the effect of UGT1A1 inhibitors has not been assessed clinically. This modeling study describes a physiologically‐based pharmacokinetic (PBPK) approach to complement the clinical DDI liability assessment and support prescription labeling. A PBPK model of vericiguat was developed based on in vitro and clinical data, verified against data from the mefenamic acid DDI study, and applied to assess the UGT1A1 DDI liability by running an in silico DDI study with the UGT1A1 inhibitor atazanavir. A minor effect with an area under the plasma concentration‐time curve (AUC) ratio of 1.12 and a peak plasma concentration ratio of 1.04 was predicted, which indicates that there is no clinically relevant DDI interaction anticipated. Additionally, the effect of potential genetic polymorphisms of UGT1A1 and UGT1A9 was evaluated, which showed that an average modest increase of up to 1.7‐fold in AUC may be expected in the case of concomitantly reduced UGT1A1 and UGT1A9 activity for subpopulations expressing non‐wild‐type variants for both isoforms. This study is a first cornerstone to qualify the PK‐Sim platform for use of UGT‐mediated DDI predictions, including PBPK models of perpetrators, such as mefenamic acid and atazanavir, and sensitive UGT substrates, such as dapagliflozin and raltegravir.
Deciphering resveratrol's role in modulating pathological pain: From molecular mechanisms to clinical relevance
Authors: Wang Biao , Jiang Hai‐Mei , Qi Lu‐Ming , Li Xiang , Huang Qun , Xie Xin , Xia Qing
Published: October 2023

Pathological pain, a multifaceted and debilitating ailment originating from injury or post‐injury inflammation of the somatosensory system, poses a global health challenge. Despite its ubiquity, reliable therapeutic strategies remain elusive. To solve this problem, resveratrol, a naturally occurring nonflavonoid polyphenol, has emerged as a potential beacon of hope owing to its anti‐inflammatory, antioxidant, and immunomodulatory capabilities. These properties potentially position resveratrol as an efficacious candidate for the management of pathological pain. This concise review summaries current experimental and clinical findings to underscore the therapeutic potential of resveratrol in pathological pain, casting light on the complex underlying pathophysiology. Our exploration suggests that resveratrol may exert its analgesic effect by the modulating pivotal signaling pathways, including PI3K/Akt/mTOR, TNFR1/NF‐κB, MAPKs, and Nrf2. Moreover, resveratrol appears to attenuate spinal microglia activation, regulate primary receptors in dorsal root sensory neurons, inhibit pertinent voltage‐gated ion channels, and curb the expression of inflammatory mediators and oxidative stress responses. The objective of this review is to encapsulate the pharmacological activity of resveratrol, including its probable signaling pathways, pharmacokinetics, and toxicology pertinent to the treatment of pathological pain. Hopefully, we aim to map out promising trajectories for the development of resveratrol as a potential analgesic.
Two‐Mode Correlated Multiphoton Bundle Emission
Authors: Wang Yi , Zou Fen , Liao Jie‐Qiao
Published: October 2023

The preparation of correlated multiphoton sources is an important research topic in quantum optics and quantum information science. Here, two‐mode correlated multiphoton bundle emission in a nondegenerate multiphoton Jaynes–Cummings model, which is comprised of a two‐level system coupled with two cavity modes is studied. The two‐level system is driven by a near‐resonant strong laser such that the Mollow regime dominates the physical processes in this system. Under certain resonance conditions, a perfect super‐Rabi oscillation between the zero‐photon state and the ()‐photon state of the two cavity modes can take place. Induced by the photon decay, the two‐mode correlated multiphoton bundle emission occurs in this system. More importantly, the results show that there is an antibunching effect between the strongly‐correlated photon bundles, so that the system behaves as an antibunched ()‐photon source. The work opens up a route toward achieving two‐mode correlated multiphoton source device, which has potential applications in modern quantum technology.
Surface analysis insight note: Multivariate curve resolution of an X‐ray photoelectron spectroscopy image
Authors: Moeini Behnam , Gallagher Neal , Linford Matthew R.
Published: October 2023

This Insight Note follows a series of three previous insight notes on X‐ray photoelectron spectroscopy image analysis that focused on the importance of analyzing the raw data, the use of summary statistics, and principal component analysis (PCA). The same X‐ray photoelectron spectroscopy image data set was analyzed in all three notes. We now show an analysis of this same data set using multivariate curve resolution (MCR). MCR is a widely used exploratory data analysis method. Because of MCR's nonnegativity constraints, it has the important advantage of producing factors that look like real spectra. That is, both its scores and loadings are positive, so its results are often more interpretable than those from PCA. The requirements for preprocessing data are also, in general, lower for MCR compared with PCA. To help determine the number of factors that best describe the data set, a series of MCR models with different numbers of factors was created. Based on the chemical reasonableness of its factors, a two‐factor model was selected. Scores plots/images show the regions of the image that correspond to these two factors.
Bayesian semiparametric variable selection with applications to periodontal data
Authors: Cai Bo , Bandyopadhyay Dipankar
Published: October 2023

A normality assumption is typically adopted for the random effects in a clustered or longitudinal data analysis using a linear mixed model. However, such an assumption is not always realistic, and it may lead to potential biases of the estimates, especially when variable selection is taken into account. Furthermore, flexibility of nonparametric assumptions (e.g., Dirichlet process) on these random effects may potentially cause centering problems, leading to difficulty of interpretation of fixed effects and variable selection. Motivated by these problems, we proposed a Bayesian method for fixed and random effects selection in nonparametric random effects models. We modeled the regression coefficients via centered latent variables which are distributed as probit stick‐breaking scale mixtures. By using the mixture priors for centered latent variables along with covariance decomposition, we could avoid the aforementioned problems and allow efficient selection of fixed and random effects from the model. We demonstrated the advantages of our proposed approach over other competing alternatives through a simulated example and also via an illustrative application to a data set from a periodontal disease study. Copyright © 2017 John Wiley & Sons, Ltd.
Hyper-IgE Syndrome in an 11 Year Old Female Presenting with Acneiform Rash
Authors: Byrne Berbie , Hefferon Tom , Harrington Rob , Leahy Marion , Murphy Annette
Published: October 2023

Hyper-IgE (HIES) is a rare, primary immunodeficiency characterised by eczema, recurrent staphylococcal infections, pneumonia, increased serum IgE and eosinophilia. We present the case of an 11-year-old girl presenting to dermatology with an acneiform facial rash and associated bacterial lymphadenitis. History was significant for otitis media, primary tooth retention, low impact wrist fracture, infantile acne and an absence of eczema or pneumonia. Investigations demonstrated mildly elevated IgE, normal eosinophils but positivity for a STAT3 gene mutation—thus representing a case of HIES presenting as an acneiform facial rash with absence of other primary immunological features.
Synthesis, characteristics, adsorption and catalytic behavior of NiO‐ZnO‐ CdO/reduced graphene oxide Nanocomposites
Authors: Lashanizadegan Maryam , Bedoreh Zahra , Mousavi Fatemeh
Published: October 2023

The nanocomposites NiO‐ZnO‐CdO/reduced graphene oxide (N‐Z‐C/rGO) were prepared using the reflux method. These nanocomposites were characterized using various techniques, including infrared spectroscopy (FTIR), Raman spectroscopy, scanning electron microscopy (SEM), electron dispersive spectroscopy (EDS), induced coupled plasma emission spectroscopy (ICP), and X‐ray diffraction (XRD). The application of the synthesized nanocomposites was investigated in two fields: the removal of azo dyes and the oxidation of certain organic compounds. To explore the use of this compound as an adsorbent, the removal of methylene blue (MB) and rhodamine B (RhB) dyes was studied. Under optimal conditions, the adsorbent absorbed MB with 98 % efficiency in 15 minutes and RhB with 96 % efficiency in 30 minutes. In the second part of the study, the performance of the nanocomposite in the oxidation of benzyl alcohol and styrene was examined. Optimal conditions for oxidizing benzyl alcohol used tert‐butyl hydroperoxide(TBHP) and acetonitrile, achieving 83 % efficiency and 92 % selectivity for benzoic acid in 6 hours. α‐methyl styrene oxidation used chloroform and TBHP, reaching 97 % efficiency and 90 % selectivity for acetophenone in 4 hours.
Microwave Synthesized Hydrophilic 4‐Oxo‐2‐phenylquinazoline‐3(4H)–carboximidamide and –Carboxamide as Privileged Small Molecule Scaffolds with Anti‐HIV‐1 Activities
Authors: Das Ranjan Kumar , Singh Aradhana , Sharma Debdulal , Rai Madhu , Paul Subrata , Gaur Ritu , Sengupta Devashish
Published: October 2023

Opportunistic infections like tuberculosis (TB) are prevalent in HIV‐infected individuals. In an approach to introducing an industrial‐scale microwave‐assisted production of agents having both antiviral and antibacterial properties, a set of hydrophilic 2,3‐substituted quinazolinones, 4‐oxo‐2‐phenylquinazoline‐3(4H)‐carboximidamide (Qg) and 4‐oxo‐2‐phenylquinazoline‐3(4H)‐carboxamide (Qu), were afforded in encouraging yields. They were obtained by treating 2‐benzamidobenzoyl chloride with guanidine hydrochloride or urea in the presence of potassium carbonate in DMF. DFT calculations were employed for geometrical optimization and vibrational frequency analysis of the compounds. Free energies of solvation (ΔGsol) of Qg, and Qu calculated using DFT lend evidence in support of their hydrophilicity The anti‐HIV‐1 activities of the small‐molecule quinazolinone derivatives Qg and Qu were investigated. The synthons under in vitro conditions inhibit the entry of HIV in receptor cells with low cytotoxicity (EC50=50.53 nM for Qu and EC50=97.92 nM for Qg). The study identifies the antiviral properties of the two benzo‐fused pyrimidine derivatives, which were earlier reported to have antitubercular activity. Our findings indicate the scope for further synthetic explorations of these quinazolinone scaffolds that can lead to developing promising alternatives in drug design, pharmaceutics, and clinical research.
Rapid and Accurate Antimicrobial Susceptibility Testing Using Label‐Free Electrical Impedance‐Based Microfluidic Platform
Authors: Chen Jiahong , Zhong Jianwei , Chang Yifu , Zhou Yinning , Koo Seok Hwee , Tan Thean Yen , Lei Hongtao , Ai Ye
Published: October 2023

Antimicrobial resistance has become a serious threat to the global public health. Accurate and rapid antimicrobial susceptibility testing (AST) allows evidence‐based prescribing of antibiotics to improve patient care and clinical outcomes. Current culture‐based AST assays are inherently limited by the doubling time of bacterial reproduction, which require at least 24 h to have a decisive result. Herein, a label‐free electrical impedance‐based microfluidic platform designed to expedite and streamline AST procedure for clinical practice is presented. Following a 30‐min exposure of bacterial samples to antibiotics, the presented high‐throughput, single‐bacterium level impedance characterization platform enables a rapid 2‐min AST assay. The platform facilitates accurate analysis of individual bacterial viability, as indicated by changes in electrical characteristics, thereby enabling the determination of antimicrobial resistance. Moreover, the potential clinical applicability of this platform is demonstrated by testing different E. coli strains against five antibiotics, yielding 100% categorical agreements compared to standard culture methods.
Sustainable development and conservation of agro‐waste coconut shell powder strengthen lightweight aluminum bio‐composite for user friendly
Authors: Kubendiran Murugan , Karthikeyan Natarajan , Kannan Chidambaram Ramesh , Manivannan Subramanian , Venkatesh Rathinavelu , Naveen Subbaiyan
Published: October 2023

The sustainable growth of advanced material in metal matrix composites receiving the eco‐friendly hazard‐free composite via recycling waste agro products attains low fabrication cost. The prime goal of this investigation is to develop and strengthen the lightweight aluminum alloy (Al7075) composite through the conservations of 0 wt%, 5 wt%, 10 wt%, and 15 wt% agro‐waste coconut shell using squeeze cast technology. The developed aluminum alloy bio‐composites are promising the best option for replacing conventional metals in several engineering applications like automotive, structural, aerospace, and others. The synthesized Al7075 alloy bio‐composites are studied its physic‐mechanical behavior tag with ASTM standards. The density results revealed nominal improvement, and its mechanical properties of hardness, ultimate tensile strength, and elastic modulus increased significantly. Sample 4 composite contained 15 wt% coconut shell powder found 2.82 ± 0.17 g/cc density with 0.716% porosity level enhanced the hardness, Ultimate tensile strength and elastic modulus of 79 ± 1.1Hv, 238 ± 1.1 MPa and 77.89 ± 2.01 GPa, respectively.
The impacts of land‐use and climate change on the Zoige peatland carbon cycle: A review
Authors: Gaffney Paul P. J. , Tang Qiuhong , Li Quanwen , Zhang Ruiyang , Pan Junxiao , Xu Ximeng , Li Yuan , Niu Shuli
Published: October 2023

The Zoige peatlands are the largest peatland area in China, and the largest high‐altitude peatland in the world. As with many peatlands worldwide, degradation from land management and climate change mean that the intact Zoige peatland area has decreased, potentially reducing the carbon (C) sink function and ecosystem services. This review summarizes current knowledge of the impacts of land‐use and climate change on the Zoige peatland C cycle in a global perspective and identifies future research and management directions. The existing literature suggests that artificial drainage carried out to lower water tables and improve grazing has a significant impact on the peatland C cycle. Drained and degraded areas may act as a net C source, through increased CO2 emissions, although the overall C balance of the Zoige peatlands is likely still a net C sink. Future climate change may also impact upon the peatland C cycle. Warming of 2°C may significantly reduce the strength of the C sink of intact peatland areas, which may shift the overall Zoige peatland C cycle balance to a net C source. The effect of warming on degraded Zoige peatlands is a major uncertainty, although the global literature suggests warming effects may be greater in degraded peatlands. Restoration of degraded peatlands (by blocking drains) may help reverse some of the impacts of degradation and gradually recover C sink function. However, there are fewer studies in Zoige peatlands than elsewhere. We conclude with several specific suggestions for future research on the peatland C cycle.

This article is categorized under:

Paleoclimates and Current Trends > Modern Climate Change

Assessing Impacts of Climate Change > Observed Impacts of Climate Change

Climate, Ecology, and Conservation > Observed Ecological Changes
Biogenic polymer nanoparticles to remove hydrophobic organic contaminants from water
Authors: Kathalingam Adaikalam , Santhoshkumar Palanisamy , Ramesh Sivalingam , Sivanesan Iyyakkannu , Kim Hyun‐Seok
Published: October 2023

Soil and water pollution is of significant concern worldwide because of the consequences of environmental degradation and harmful effects on human health. Water bodies are very much polluted by various organic and inorganic pollutants by different human activities, including industrial wastes. Environmental pollution remains high because of urbanization‐induced industrial developments and human lifestyle. It accumulates pollutants in the environment including plants and living organisms. Even mothers' milk is poisoned because of the uncontrolled, widespread increase in pollution. The discharge levels of organic hydrophobic contaminants in the water and soil are increasing rapidly. This severe pollution must be remediated to upgrade the environment and ensure the safety of human beings. It is vital to eradicate soil and water pollution to guarantee sufficient food and water. Different techniques available to remove the pollutants vary according to the type of pollutants. Hydrophobic contaminants are more dangerous than heavy metals and other pollutants; they cannot be easily removed, requiring special care. Hydrophobic organoxenobiotics released in the environment pose severe contamination in soil and water. Therefore, developing efficient and cost‐effective processes is necessary to remove hydrophobic contaminants from soil and water. With nanoparticle‐mediated remediation techniques, the green‐synthesized nanoparticles exhibit improved performance. This review consolidates reports on the remediation techniques of hydrophobic contaminants, focusing on green‐synthesized remediation agents. The very limited works on green synthesis of polymeric nanoparticles, particularly polyurethane‐based materials for organic contaminants removal demand more attention in this area.

Practitioner Points

Consolidated the effects of hydrophobic organic and plastic contaminants on environment degradation.

Summarized the advantages of green synthesized polymer nanoparticles for efficient removal of hydrophobic contaminants.

Discussed the different sources of pollution and remediation techniques referring 112 research works.
On-shell operator construction in the effective field theory of gravity
Authors: Li Hao-Lin , Ren Zhe , Xiao Ming-Lei , Yu Jiang-Hao , Zheng Yu-Hui
Published: October 2023

Abstract

We construct the on-shell amplitude basis and the corresponding effective operators for generic modified gravity theory, such as pure gravity with higher derivatives, scalar-tensor gravity, Einstein-Yang-Mills, etc. Taking the Weyl tensor as the building block, we utilize the Young tensor technique to obtain independent operators, without equation of motion and total derivative redundancies. We update our algorithm and vastly increase the speed for finding the monomial basis (m-basis) of effective operators expressed in terms of Weyl tensors with Lorentz indices, the familiar form for the General Relativity community. Finally, we obtain the complete and independent amplitude and operator basis for GRSMEFT and GRLEFT up to mass dimension 10.
Comparing nanobody and aptamer-based capacitive sensing for detection of interleukin-6 (IL-6) at physiologically relevant levels
Authors: Sánchez-Salcedo Raquel , Miranda-Castro Rebeca , de-los-Santos-Álvarez Noemí , Lobo-Castañón María Jesús , Corrigan Damion K.
Published: October 2023

A major societal challenge is the development of the necessary tools for early diagnosis of diseases such as cancer and sepsis. Consequently, there is a concerted push to develop low-cost and non-invasive methods of analysis with high sensitivity and selectivity. A notable trend is the development of highly sensitive methods that are not only amenable for point-of-care (POC) testing, but also for wearable devices allowing continuous monitoring of biomarkers. In this context, a non-invasive test for the detection of a promising biomarker, the protein Interleukin-6 (IL-6), could represent a significant advance in the clinical management of cancer, in monitoring the chemotherapy response, or for prompt diagnosis of sepsis. This work reports a capacitive electrochemical impedance spectroscopy sensing platform tailored towards POC detection and treatment monitoring in human serum. The specific recognition of IL-6 was achieved employing gold surfaces modified with an anti-IL6 nanobody (anti-IL-6 VHH) or a specific IL-6 aptamer. In the first system, the anti-IL-6 VHH was covalently attached to the gold surface using a binary self-assembled-monolayer (SAM) of 6-mercapto-1-hexanol (MCH) and 11-mercaptoundecanoic acid. In the second system, the aptamer was chemisorbed onto the surface in a mixed SAM layer with MCH. The analytical performance for each label-free sensor was evaluated in buffer and 10% human serum samples and then compared. The results of this work were generated using a low-cost, thin film eight-channel gold sensor array produced on a flexible substrate providing useful information on the future design of POC and wearable impedance biomarker detection platforms.
Optimal Control of Nonlocal Continuity Equations: Numerical Solution
Authors: Chertovskih Roman , Pogodaev Nikolay , Staritsyn Maxim
Published: October 2023

The paper addresses an optimal ensemble control problem for nonlocal continuity equations on the space of probability measures. We admit the general nonlinear cost functional, and an option to directly control the nonlocal terms of the driving vector field. For this problem, we design a descent method based on Pontryagin’s maximum principle (PMP). To this end, we derive a new form of PMP with a decoupled Hamiltonian system. Specifically, we extract the adjoint system of linear nonlocal balance laws on the space of signed measures and prove its well-posedness. As an implementation of the designed descent method, we propose an indirect deterministic numeric algorithm with backtracking. We prove the convergence of the algorithm and illustrate its modus operandi by treating a simple case involving a Kuramoto-type model of a population of interacting oscillators.
An intramolecular disulphide bond in human 4E-T affects its binding to eIF4E1a protein
Authors: Zuberek Joanna , Warzecha Marek , Dobrowolski Mateusz , Modrak-Wojcik Anna
Published: October 2023

The cap at the 5’terminus of mRNA is a key determinant of gene expression in eukaryotic cells, which among others is required for cap dependent translation and protects mRNA from degradation. These properties of cap are mediated by several proteins. One of them is 4E-Transporter (4E-T), which plays an important role in translational repression, mRNA decay and P-bodies formation. 4E-T is also one of several proteins that interact with eukaryotic initiation factor 4E (eIF4E), a cap binding protein which is a key component of the translation initiation machinery. The molecular mechanisms underlying the interactions of these two proteins are crucial for mRNA processing. Studying the interactions between human eIF4E1a and the N-terminal fragment of 4E-T that possesses unstructured 4E-binding motifs under non-reducing conditions, we observed that 4E-T preferentially forms an intramolecular disulphide bond. This “disulphide loop” reduces affinity of 4E-T for eIF4E1a by about 300-fold. Considering that only human 4E-T possesses two cysteines located between the 4E binding motifs, we proposed that the disulphide bond may act as a switch to regulate interactions between the two proteins.

Graphical Abstract
Machine learning based on radiomics features combing B-mode transrectal ultrasound and contrast-enhanced ultrasound to improve peripheral zone prostate cancer detection
Authors: Sun Ya , Fang Jingyang , Shi Yanping , Li Huarong , Wang Jiajun , Xu Jingxu , Zhang Bao , Liang Lei
Published: October 2023

Purpose

To construct machine learning models based on radiomics features combing conventional transrectal ultrasound (B-mode) and contrast-enhanced ultrasound (CEUS) to improve prostate cancer (PCa) detection in peripheral zone (PZ).

Methods

A prospective study of 166 men (72 benign, 94 malignant lesions) with targeted biopsy-confirmed pathology who underwent B-mode and CEUS examinations was performed. Risk factors, including age, serum total prostate-specific antigen (tPSA), free PSA (fPSA), f/t PSA, prostate volume and prostate-specific antigen density (PSAD), were collected. Time-intensity curves were obtained using SonoLiver software for all lesions in regions of interest. Four parameters were collected as risk factors: the maximum intensity (IMAX), rise time (RT), time to peak (TTP), and mean transit time (MTT). Radiomics features were extracted from the target lesions from B-mode and CEUS imaging. Multivariable logistic regression analysis was used to construct the model.

Results

A total of 3306 features were extracted from seven categories. Finally, 32 features were screened out from radiomics models. Five models were developed to predict PCa: the B-mode radiomics model (B model), CEUS radiomics model (CEUS model), B-CEUS combined radiomics model (B-CEUS model), risk factors model, and risk factors-radiomics combined model (combined model). Age, PSAD, tPSA, and RT were significant independent predictors in discriminating benign and malignant PZ lesions (P < 0.05). The risk factors model combing these four predictors showed better discrimination in the validation cohort (area under the curve [AUC], 0.84) than the radiomics images (AUC, 0.79 on B model; AUC, 0.78 on CEUS model; AUC, 0.83 on B-CEUS model), and the combined model (AUC: 0.89) achieved the greatest predictive efficacy.

Conclusion

The prediction model including B-mode and CEUS radiomics signatures and risk factors represents a promising diagnostic tool for PCa detection in PZ, which may contribute to clinical decision-making.
An optimized protocol for the generation and monitoring of conditional orthotopic lung cancer in the KP mouse model using an adeno-associated virus vector compatible with biosafety level 1
Authors: Deng Haibin , Ge Huixiang , Dubey Christelle , Losmanova Tereza , Medová Michaela , Konstantinidou Georgia , Mutlu Seyran Mathilde , Birrer Fabienne Esther , Brodie Tess Melinda , Stroka Deborah , Wang Wenxiang , Peng Ren-Wang , Dorn Patrick , Marti Thomas Michael
Published: October 2023

Background

The inducible Kras/p53 lung adenocarcinoma mouse model, which faithfully recapitulates human disease, is routinely initiated by the intratracheal instillation of a virus-based Cre recombinase delivery system. Handling virus-based delivery systems requires elevated biosafety levels, e.g., biosafety level 2 (BSL-2). However, in experimental animal research facilities, following exposure to viral vectors in a BSL-2 environment, rodents may not be reclassified to BSL-1 according to standard practice, preventing access to small animal micro-computed tomography (micro-CT) scanners that are typically housed in general access areas such as BSL-1 rooms. Therefore, our goal was to adapt the protocol so that the Cre-induced KP mouse model could be handled under BSL-1 conditions during the entire procedure.

Results

The Kras-Lox-STOP-Lox-G12D/p53 flox/flox (KP)-based lung adenocarcinoma mouse model was activated by intratracheal instillation of either an adenoviral-based or a gutless, adeno-associated viral-based Cre delivery system. Tumor growth was monitored over time by micro-CT. We have successfully substituted the virus-based Cre delivery system with a commercially available, gutless, adeno-associated, Cre-expressing vector that allows the KP mouse model to be handled and imaged in a BSL-1 facility. By optimizing the anesthesia protocol and switching to a microscope-guided vector instillation procedure, productivity was increased and procedure-related complications were significantly reduced. In addition, repeated micro-CT analysis of individual animals allowed us to monitor tumor growth longitudinally, dramatically reducing the number of animals required per experiment. Finally, we documented the evolution of tumor volume for different doses, which revealed that individual tumor nodules induced by low-titer AAV-Cre transductions can be monitored over time by micro-CT.

Conclusion

Modifications to the anesthesia and instillation protocols increased the productivity of the original KP protocol. In addition, the switch to a gutless, adeno-associated, Cre-expressing vector allowed longitudinal monitoring of tumor growth under BSL-1 conditions, significantly reducing the number of animals required for an experiment, in line with the 3R principles.
The Efficacy and Safety of Tirofiban Use in Endovascular Thrombectomy for Intravenous Thrombolysis Applicable Patients with Large Vessel Occlusion Stroke—a Post Hoc Analysis from the Direct-MT Trial
Authors: Zhang Yingying , Zhang Ping , Tao Anyang , Wang Xinliang , Ying Jiangxian , Wang Zhimin , Yang Pengfei , Zhang Yongwei , Zhang Lei , Li Zifu , Zhang Meng , Xu Chenghua , Liu Jianmin ,   on behalf of The Direct-MT Investigators
Published: October 2023

Purpose

The purpose of the study was to evaluate the efficacy and safety of tirofiban use in endovascular thrombectomy for intravenous thrombolysis applicable patients of large vessel occlusion stroke with data from Direct-MT trial.

Materials and Methods

Direct-MT was the first randomized controlled trial to prove the non-inferiority of thrombectomy alone to bridging therapy (intravenous thrombolysis before thrombectomy) for large vessel occlusion stroke. Patients who underwent endovascular procedure were included and divided into thrombectomy-alone group and bridging therapy group. The effect of tirofiban use on 90 days MRS distribution, MRS 0–2 and mortality, successful reperfusion, the ASPECTS and outcome lesion volume of index stroke, re-occlusion of the treated vessel, futile recanalization and safety outcomes were further evaluated in both groups after adjustment for relevant confounding factors. The interaction between tirofiban and rt-PA was also assessed.

Results

Of 639 patients included in this analysis, 180 patients underwent thrombectomy with tirofiban use (28.2%). Patients with tirofiban use had lower percentage of bridging therapy (41.1% vs 54.3%, P = 0.003), higher proportion of large artery atherosclerosis (P < 0.001) and more emergent stenting (30.56% vs 6.97%, P < 0.001). After adjustment for confounding factors, the 90-day modified Rankin Scale distribution, successful final recanalization rate, outcome lesion volume of index stroke on CT and intracranial hemorrhage risk showed no difference after tirofiban use in thrombectomy-alone group and in bridging therapy group. No interaction effect between tirofiban and rt-PA was detected.

Conclusion

Based on data from Direct-MT trial, tirofiban is a safe medication for intravenous thrombolysis applicable patients with large vessel occlusion stroke undergoing thrombectomy.

Level of Evidence

Level 3, cohort study of randomized trial.
Dynamic pricing for shared mobility systems based on idle time data
Authors: Müller Christian , Gönsch Jochen , Soppert Matthias , Steinhardt Claudius
Published: October 2023

In most major cities today, various shared mobility systems such as car or bike sharing exist. Maintaining these systems is challenging, and, thus, public and private providers strive to improve operational performance. An important metric which is regularly recorded and monitored in practice for this purpose is idle time, i.e., the time a vehicle stands unused between two rentals. Usually, it is available for different temporal and spatial granularities. At the same time, dynamic pricing has been shown to be an efficient means for increasing operational performance in shared mobility systems, but data necessary for traditional dynamic pricing approaches, like unconstrained demand, is much less available in practice. Thus, dynamic pricing based on idle time data appears promising and first ideas have been proposed. However, the existing approaches are based either on simple business rules or on myopic optimization. In this work, we develop a novel dynamic pricing approach that determines prices by online optimization and thereby anticipates future profits through the integration of idle time data. The core idea is quantifying the remaining profitable time by using idle times. With regard to application in practice, the developed approach is generic in the sense that different types of readily available historical idle time data can be seamlessly integrated, meaning data of different spatio-temporal granularities. In an extensive numerical study, we demonstrate that the operational performance increases with higher granularity and that the approach with the highest one outperforms current pricing practice by up to 11% in terms of profit.
Vessel wall MRI in moyamoya disease: arterial wall enhancement varies depending on age, arteries, and disease progression
Authors: Tagawa Hiroshi , Fushimi Yasutaka , Funaki Takeshi , Nakajima Satoshi , Sakata Akihiko , Okuchi Sachi , Hinoda Takuya , Grinstead John , Ahn Sinyeob , Hidaka Yu , Yoshida Kazumichi , Miyamoto Susumu , Nakamoto Yuji
Published: October 2023

Objective

To investigate the relationship of followings for patients with moyamoya disease (MMD): arterial wall enhancement on vessel wall MRI (VW-MRI), cross-sectional area (CSA), time-of-flight MR angiography (MRA), age, locations from intracranial internal carotid artery (ICA) to proximal middle cerebral artery (MCA), disease progression, and transient ischemic attack (TIA).

Methods

Patients who underwent VW-MRI between October 2018 and December 2020 were enrolled in this retrospective study. We measured arterial wall enhancement (enhancement ratio, ER) and CSA at five sections of ICA and MCA. Also, we scored MRA findings. Multiple linear regression (MLR) analysis was performed to explore the associations between ER, age, MRA score, CSA, history of TIA, and surgical revascularization.

Results

We investigated 102 sides of 51 patients with MMD (35 women, 16 men, mean age 31 years ± 18 [standard deviation]). ER for MRA score 2 (signal discontinuity) was higher than ER for other scores in sections D (end of ICA) and E (proximal MCA) on MLR analysis. ER in section E was significantly higher in patients for MRA score 2 with TIA history than without. ER significantly increased as CSA increased in section E, which suggests ER becomes less in decreased CSA due to negative remodeling.

Conclusion

Arterial wall enhancement in MMD varies by age, location, and disease progression. Arterial wall enhancement may be stronger in the progressive stage of MMD. Arterial wall enhancement increases with history of TIA at proximal MCA, which may indicate the progression of the disease.

Clinical relevance statement

Arterial wall enhancement in moyamoya disease varies by age, location of arteries, and disease progression, and arterial wall enhancement may be used as an imaging biomarker of moyamoya disease.

Key Points

It has not been clarified what arterial wall enhancement in moyamoya disease represents.

Arterial wall enhancement in moyamoya disease varies by age, location of arteries, and disease progression.

Arterial wall enhancement in moyamoya disease increases as the disease progresses.

Graphical abstract
C-section technique vs minilaparotomy after minimally invasive uterine surgery: a retrospective cohort study
Authors: Della Corte Luigi , Guarino Maria Chiara , Vitale Salvatore Giovanni , Angioni Stefano , Mercorio Antonio , Bifulco Giuseppe , Giampaolino Pierluigi
Published: October 2023

Purpose

Uterine leiomyomas are benign uterine tumors. The choice of surgical treatment is guided by patient's age, desire to preserve fertility or avoid "radical" surgical interventions such as hysterectomy. In laparotomy, the issue of extracting the fibroid from the cavity does not arise. However, in laparoscopy and robotic surgery, this becomes a challenge. The aim of the present study was to determine the optimal surgical approach for fibroid extraction following laparoscopic or robotic myomectomy in terms of postoperative pain, extraction time, overall surgical time, scar size, and patient satisfaction.

Methods

A total of 51 patients met the inclusion criteria and were considered in our analysis: 33 patients who had undergone the "ExCITE technique" (Group A), and 18 patients a minilaparotomy procedure (Group B), after either simple myomectomy, multiple myomectomy, supracervical hysterectomy, or total hysterectomy. The diagnosis of myoma was histologically confirmed in all cases.

Results

Regarding the postoperative pain evaluation, at 6 h, patients reported 4 [3–4] vs 6 [5.3–7] on the VAS in Group A and B, as well as at 12 h, 2 [0–2] vs 3.5 [2.3–4] in Group A and B, respectively: both differences were statistically significant (p < 0.001). No statistically significant difference at 24 h from surgery was found. All patients in Group A were satisfied with the ExCITE technique, while in Group B only 67% of them. The length of the hospital stay was significantly shorter in Group A as compared to Group B (p = 0.007). In terms of the operative time for the extraction of the surgical specimen, overall operative time, and the scar size after the surgery, there was a statistically significant difference for those in Group A.

Conclusion

The ExCITE technique does not require specific training and allows the surgeon to offer a minimally invasive surgical option for patients, with also an aesthetic result. It is a safe and standardized approach that ensures tissue extraction without the need for mechanical morcellation.
Fabricating a designer capsule phase microextraction platform based on sol–gel Carbowax 20M-zwitterionic ionic liquid composite sorbent for the extraction of lipid-lowering drugs from human urine samples
Authors: Kechagia Argyroula , Manousi Natalia , Kabir Abuzar , Furton Kenneth G. , Zacharis Constantinos K.
Published: October 2023

A sol–gel Carbowax 20 M/3-[(3-Cholamidopropyl) dimethyl ammonio]-1-propanesulfonate composite sorbent-based capsule phase microextraction device has been fabricated and characterized for the determination of four statins (pravastatin, rosuvastatin, pitavastatin, and atorvastatin) in human urine. The presence of ionizable carboxyl functional groups in statins requires pH adjustment of the sample matrix to ensure that the target molecules are in their protonated form (pH should be 2 units below their pKa values) which not only is cumbersome but also risks unintended contamination of the sample. This challenge was addressed by introducing zwitterionic ionic liquid in addition to neutral, polar Carbowax 20 M polymer in the sol–gel-derived composite sorbent. As such, the composite zwitterionic multi-modal sorbent can simultaneously extract neutral, cationic, and anionic species. This particular attribute of the composite sorbent eliminates the necessity of the matrix pH adjustment and consequently simplifies the overall sample preparation workflow. Various experimental parameters such as the sample amount, extraction time, salt addition, stirring rate, and elution solvent type that may affect the extraction performance of the statins were investigated using a central composite design and the one-parameter-at-a-time approach. The analytes and the internal standard were separated on a C18 column with gradient elution using phosphate buffer (20 mM, pH 3) and acetonitrile as mobile phase. The analytes were detected at 237 nm. The method was validated, and linearity was observed in the range 0.10–2.0 μg mL−1 for all compounds. The method precision was better 9.9% and 10.4% for intra-day and inter-day, respectively, while the relative recoveries were acceptable, ranging between 83.4 and 116% in all cases. Method greenness was assessed using the ComplexGAPI index. Finally, the method’s applicability was demonstrated in the determination of the statins in authentic human urine after oral administration of pitavastatin and rosuvastatin-containing tablets.

Graphical abstract
Pointwise multipliers for Besov spaces $$B^{0,b}_{p,\infty }({\mathbb {R}}^n)$$ with only logarithmic smoothness
Authors: Li Ziwei , Sickel Winfried , Yang Dachun , Yuan Wen
Published: October 2023

In this article, we establish a characterization of the set $$M(B^{0,b}_{p,\infty }({\mathbb {R}}^n))$$

M
(

B

p
,
∞

0
,
b

(

R

n

)

)

of all pointwise multipliers of Besov spaces $$B^{0,b}_{p,\infty }({\mathbb {R}}^n)$$

B

p
,
∞

0
,
b

(

R

n

)

with only logarithmic smoothness $$b\in {\mathbb {R}}$$

b
∈
R

in the special cases $$p=1$$

p
=
1

and $$p=\infty $$

p
=
∞

. As applications of these two characterizations, we clarify whether or not the three concrete examples, namely characteristic functions of open sets, continuous functions defined by differences, and the functions $$e^{ik\cdot x}$$

e

i
k
·
x

with $$k\in {\mathbb {Z}}^n$$

k
∈

Z

n

and $$x\in {\mathbb {R}}^n$$

x
∈

R

n

, are pointwise multipliers of $$B^{0,b}_{1,\infty }({\mathbb {R}}^n)$$

B

1
,
∞

0
,
b

(

R

n

)

and $$B^{0,b}_{\infty ,\infty }({\mathbb {R}}^n)$$

B

∞
,
∞

0
,
b

(

R

n

)

, respectively; furthermore, we obtain the explicit estimates of $$\Vert e^{ik \cdot x}\Vert _{M(B^{0,b}_{1,\infty }({\mathbb {R}}^n))}$$

‖

e

i
k
·
x

‖

M
(

B

1
,
∞

0
,
b

(

R

n

)

)

and $$\Vert e^{ik \cdot x}\Vert _{M(B^{0,b}_{\infty ,\infty }({\mathbb {R}}^n))}$$

‖

e

i
k
·
x

‖

M
(

B

∞
,
∞

0
,
b

(

R

n

)

)

. In the case where $$p\in (1,\infty )$$

p
∈
(
1
,
∞
)

, we give some sufficient conditions and some necessary conditions of the pointwise multipliers of $$B^{0,b}_{p,\infty }({\mathbb {R}}^n)$$

B

p
,
∞

0
,
b

(

R

n

)

and a complete characterization of $$M(B^{0,b}_{p,\infty }({\mathbb {R}}^n))$$

M
(

B

p
,
∞

0
,
b

(

R

n

)

)

is still open. However, via a different method, we are still able to accurately calculate $$\Vert e^{ik \cdot x}\Vert _{M(B^{0,b}_{p,\infty }({\mathbb {R}}^n))}$$

‖

e

i
k
·
x

‖

M
(

B

p
,
∞

0
,
b

(

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n

)

)

, $$k\in {\mathbb {Z}}^n$$

k
∈

Z

n

, in this situation. The novelty of this article is that most of the proofs are constructive and these constructions strongly depend on the logarithmic structure of Besov spaces under consideration.
Epilepsieüberwachungsgeräte bei Kindern und Jugendlichen
Authors: Borusiak Peter , Bast Thomas , Haberlandt Edda , Wiegand Gert
Published: October 2023

Hintergrund

Viele Eltern der Kinder und Jugendlichen mit Epilepsien wünschen eine Überwachung insbesondere von nächtlichen Anfällen. Daten zu den einzelnen Geräten stammen überwiegend aus einem klinischen Setting an Erwachsenen. Alltagsbezogene Daten für Kinder und Jugendliche fehlen.

Ziel der Arbeit

Es erfolgte die Sammlung von alltagsbezogenen Informationen und Einschätzungen über den Einsatz verschiedener Überwachungsgeräte bei Kindern und Jugendlichen im häuslichen Setting.

Material und Methoden

In Zusammenarbeit mit dem Elternverband (e.b.e.) erfolgte vom 01.03.2023 bis 16.04.2023 eine Querschnittuntersuchung via eine webbasierte Umfrage mittels SoSci-Survey.

Ergebnisse

Für die Altersgruppe < 18 Jahre lagen 153 auswertbare Datensätze vor. Hiervon war bei 129 Teilnehmenden zumindest über einen Zeitraum ein Überwachungsgerät im Einsatz. Die Gruppen mit oder ohne Anfallsüberwachung unterschieden sich nicht hinsichtlich demografischer und epilepsiebezogener Faktoren. Es kam eine Vielzahl von Geräten quer durch alle Altersgruppen zum Einsatz, ohne dass eine eindeutige Präferenz erkennbar war. Die am häufigsten verwendeten Geräte waren NightWatch® (N = 39), VitaGuard® 3100/310 (N = 18) und die verschiedenen Epi-Care®-Modelle (N = 16). Im Elternurteil wurden Benutzerfreundlichkeit, Sicherheit und Zuverlässigkeit und Eignung für die Anfallsüberwachung benotet, wobei sich kein klares und eindeutiges Bild ergab.

Diskussion

Letztendlich kann auch auf Basis unserer Daten keine allgemeingültige Empfehlung für oder gegen ein bestimmtes Gerät ausgesprochen werden. Der Bericht hilft Patient*innen und ihren Ärzt*innen, einen Einblick in den Alltag mit nächtlicher Überwachung zu bekommen, und kann dazu beitragen, sich ein eigenes Bild je nach Präferenzen zu machen.
Effect of CITES Appendix I listing on illegal pangolin trade as gauged from seizure reports in Indonesia
Authors: Nijman Vincent
Published: October 2023

Pangolins, one of the most heavily trafficked animals, have become the poster child for the illegal wildlife trade. Pangolins are protected throughout their range and their international trade has been regulated through the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Assessing the effectiveness of trade regulations, such as the listing of all pangolins on CITES Appendix I in 2016 precluding all international trade, can be done by analysis of seizure reports. I report 81 large seizures within Indonesia over the last 12 years, the equivalent of 18,024 pangolins representing a value of USD9.42 million. In Indonesia, the number of seizures remained stable at around seven a year. There was a significant decrease in the number of seized pangolin equivalents, from 3000 to 4000 in 2011 and 2012 to 400 to 600 in 2021 and 2022. A break point analysis showed that any changes in this trend did not coincide with changes in international trade regulations. Seizures were made in 17/22 provinces where pangolins occur. At the provincial level seizures or the number of confiscated pangolins was not linked to minimum wage, area, human population, or international connectiveness. Despite the international nature of the pangolin trade, where reported, suspects that were arrested were Indonesian nationals. Over time the proportion of seizures comprising solely of scales has increased from ~ 5 to 100%. These observations of seizures of large amounts of pangolin scales, in the absence of bodies, carcasses, or meat, suggest there is a hidden trade in these parts, in Indonesia and/or elsewhere. There is no clear support that the CITES Appendix I listing had a direct effect on the pangolin trade within Indonesia.