bluuebunny/crossref_metadata_2025 huggingface dataset:
Amelioration of propionic acid‐induced autism‐like behaviors in rats by fenofibrate: A focus on reduction of brain galectin‐3 levels
Authors: Erdogan Mumin Alper , Akbulut Mine Ceren , Altuntaş İlknur , Tomruk Canberk , Uyanıkgil Yiğit , Erbaş Oytun
Published: November 2024

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and repetitive behaviors. This study examines the effects of fenofibrate on a propionic acid (PPA)‐induced rat model of ASD, focusing on behavioral changes, inflammatory markers, and histological findings.

Materials and Methods

Thirty male Wistar rats were divided into three groups: a control group, a group receiving PPA and saline, and a group treated with PPA and fenofibrate for 15 days. Behavioral assessments, including the three‐chamber sociability test, open‐field test, and passive avoidance learning, were conducted. Biochemical analyses measured TNF‐α, NGF, IL‐17, IL‐2, and galectin‐3 levels in brain tissues. Histological evaluations focused on Purkinje neuron counts in the cerebellum and neuronal changes in the CA1 and CA3 regions of the hippocampus, along with glial fibrillary acidic protein (GFAP) levels.

Results

Fenofibrate treatment significantly improved behavioral outcomes, reducing autism‐like behaviors compared to the PPA/saline group. Biochemically, the PPA/saline group showed elevated levels of malondialdehyde, TNF‐α, IL‐2, IL‐17, and galectin‐3, which were reduced following fenofibrate treatment. Histologically, the PPA/saline group exhibited fewer, dysmorphic Purkinje neurons and increased glial activity in the CA1 region, both of which were ameliorated by fenofibrate treatment.

Conclusion

Fenofibrate shows promise in mitigating autism‐like behaviors in a rat model of ASD, likely due to its antioxidative and neuroprotective properties, which contribute to preserving neuronal integrity and reducing inflammation.
Synergistic Regulation of DNA Morphology by Metal Cations and Low pH
Authors: Wang Xia , Wang Ying , Gao Mingyan , Hou Fengyan , Wang Junxi , Wang Jingyu , Li Ye , Wang Zuobin
Published: November 2024

As a flexible biomolecule, the spatial structure of DNA is variable. The effects of concentration, metal cations, and low pH on DNA morphology were studied. For the high concentration of DNA, the cross‐linked branch‐like or network structures were formed. For the low concentration of DNA, isolated, random and freely loose linear DNA chains were presented. These phenomena were related to the intermolecular interactions. Branch‐like DNA structures were reformed with the addition of metal cations to the low concentration of DNA at pH 7–4, suggesting the negative charges of DNA were neutralized, thus transforming the spatial structure of DNA into a low charge density morphology and presenting the hypochromic effect. Compared to the monovalent alkaline metal cations, more negative charges of DNA were screened by the alkaline‐earth metal cations. Distinct DNA morphologies were observed for pH 3. The linear and condensed DNA structures were simultaneously observed, which was met regardless of the solution with or without the addition of metal cations. This was further confirmed by the absorbance of DNA. Compared to the pure DNA, bulky and aggregated DNA collapsed structures were formed when the sodium and magnesium cations were added to the reaction solution. In addition, it was verified that the condensed DNA structures failed to revert back to the chain structure by neutralizing acidic solutions with alkali, but the compacted DNA spheres became loose. The conductivities of various DNA morphologies were measured. They were morphology‐dependent. This study provides guidance for the behavior of DNA in the acidic solutions and further promotes the application of DNA in DNA‐based nano‐optoelectronic devices.
Effect of gypsum on transport of IMX‐104 constituents in overland flow under simulated rainfall
Authors: Polyakov Viktor , Beal Samuel , Meding Stephen Mercer , Dontsova Katerina
Published: November 2024

Residue of energetic formulations, which is deposited on military training grounds following incomplete detonation, poses biotic hazards. This residue can be transported off‐site, adsorb to soil clays and organic matter, transform or degrade, or taken up by plants and animals. Its harmful effects can be mitigated by localizing the energetics at the site of initial deposition using soil amendments and allowing them to bio‐ and photodegrade in situ. Small plots with coarse loamy soil were used to study the effect of gypsum (CaSO4·2H2O) on transport and redistribution under simulated rainfall of various sizes of insensitive munition explosive (IMX)‐104 particles, which consist of 3‐nitro‐1,2,4‐triazol‐5‐one (NTO), 2,4‐dinitroanisole (DNAN), hexahydro‐1,3,5‐trinitro‐1,3,5‐triazine (RDX), and octahydro‐1,3,5,7‐tertranitro‐1,3,5,7‐tetrazocine (HMX). The addition of gypsum more than doubled infiltration and decreased sediment loss by 16% compared to the control. The post‐rainfall mass balance of IMX‐104 in the order from greater to smaller pools was as follows: (1) soil surface retention, (2) off‐site loss to overland flow, and (3) sub‐surface infiltration. Overall, the application of gypsum significantly decreased concentration and the total mass loss of dissolved DNAN, RDX, and HMX in surface runoff. In addition, gypsum significantly decreased (for NTO, DNAN, and HMX) or delayed (for NTO, DNAN, RDX, and HMX) the peak discharge of <2 mm particulate energetics. The infiltration of NTO in the gypsum treatment was fivefold greater than in the control. Moreover, DNAN and RDX were also present in infiltration, while in the gypsum‐free control none were found. Gypsum shifted the total mass balance of energetics toward subsurface flow. This study indicates that gypsum may decrease off‐site transport of energetic constituents in the soils that are subject to surface sealing.
Antioxidant and Antiapoptotic Effects of Selenium And Nano Selenium‐Loaded Exosomes on Hepatic Dysfunction of Type 1 Diabetic Rats
Authors: Alahmari Layla A. , Ali Lashin S. , Fansa Hoda A. , Alshaya Dalal S. , Al‐Salmi Fawziah A. , El‐Hallous Ehab I. , Eldesoqui Mamdouh , Gad Elsaid Fahmy , Fayad Eman , El‐Mansy Ahmed A. , Alsharif Ghadi , Khalil Dlovan Y. , Mahmood Maryam Bakir , Khalil Rozhan Yassin , Rashwan Hanan M. , El‐Sawah Shady G.
Published: November 2024

Mesenchymal stem cells‐derived exosomes (MSCs‐EXs) applications have brought a key breakthrough in treating type 1 diabetes mellitus (T1DM) and its diabetic complications. However, various recent strategies aimed to construct prominent engineered EXs with greater precision and higher efficiency for diabetes syndrome were conducted. In this research, we seek to enhance the medicinal potentialities of MSCs‐EXs on type 1 diabetic rats' hepatic complications, via loading with either selenium (Se) or nano selenium (NSe) particles. For consecutive 4‐weeks, rats were divided into 8 groups as; control, EXs, EXs + Se, EXs + NSe, STZ‐diabetic (D), D + EXs, D + EXs + Se, and D + EXs + NSe groups. The three diabetic‐treated groups manifested a significant reduction in hepatic contents of oxidative stress (OS) (MDA, NO, and H2O2) inflammatory (IL‐6, TNF‐α, and TGF‐β), and apoptotic (P53, BAX, caspase‐3, and Bcl2) markers, with marked elevation in hepatic antioxidant levels (GSH, GPX, SOD, and CAT). Such results were supported by the marked diminish in serum total proteins, liver function enzymes (AST, ALT, and bilirubin), and both serum and liver lipid profile fractions. In addition, hepatic histological examination showed marked improvement in liver architecture of all treated diabetic rats' groups, compared to diabetic untreated rats. Significantly, diabetic rats with EXs loaded with NSe exhibited the most therapeutic superiority.
Fibrinogen concentrate use in the operating theatre at a quaternary hospital in Australia
Authors: Ziser Kate Elizabeth Doreen , Bullock Madeline , Coghill Brett , Al‐Kureshy Sarah , Nihal Aaron , Bendeich Jess
Published: November 2024

At our quaternary teaching hospital in Queensland, Australia, there has been a rapid increase from 2019 to 2022 in the usage of fibrinogen concentrate (FC) in preference to cryoprecipitate for cardiac surgery. FC is indicated for patients having major trauma requiring haemostatic resuscitation, major intraoperative haemorrhage, or liver transplant patients with major intraoperative haemorrhage. These patients must exhibit severe hypofibrinogenaemia, which is assessed using assay cut‐offs of thromboelastogram (TEG) (citrated functional fibrinogen [CFF] ≤ 10 mm) or rotational thromboelastometry (ROTEM) (FIBTEM A5 ≤ 8 mm). FC usage over cryoprecipitate for cardiac surgery is an ongoing debate due to advantages such as dose predictability, rapid reconstitution, viral inactivation, and minimal transfusion‐related adverse events; however, it is expensive. The aim of this study was to capture prescribing patterns of FC and appropriateness against local guidelines. Retrospective data were analysed, and the practice was compared to hospital guidelines. Data from 52 patients over a 4‐year period (2019–2022) showed intraoperative haemorrhage was the leading indication for FC use (65%, n = 34), followed by liver transplantation (27%, n = 14), and major trauma (8%, n = 4). When breaking down the cause of intraoperative haemorrhage, cardiothoracic surgery, both elective (50%, n = 17) and emergency procedures (41%, n = 14), accounted for 91% of all operative bleeding requiring FC. There were 34 (65%) of 52 patients who received a differing dose of FC compared to what was recommended in the hospital guideline, with 50% (n = 17) receiving a higher than recommended dose and 50% (n = 17) receiving lower than recommended doses. This project was exempt due to the local policy requirements that constitute research by the Metro South Human Research Ethics Committee (Reference no: CM2305202303). The justification for this exemption was as follows: the study presented no foreseeable risk of patient harm as it involved evaluation of standard care involved the use of existing non‐identifiable patient records.
Site‐specific effects of fertilizer on hay and grain yields of oats: evidence from large‐scale field experiments
Authors: Mao Liping , Zhang Hongbo , Yang Zengnan , Li Yuan , Shen Yuying
Published: November 2024

BACKGROUND

Oat (Avena sativa L.) is a valuable crop due to its strong adaptability to marginal environments, making it an important component of agricultural systems in regions where other cereals may not thrive. The application of chemical fertilizer can influence oat hay and grain yield significantly. However, large‐scale meta‐analytical studies of the size and variability of oat hay and grain yields in response to fertilizer addition are still lacking. Based on 83 studies worldwide, this meta‐analysis quantifies the impact of the addition of fertilizer on oat hay and grain yields under varying environmental conditions (e.g., soil nutrient levels, texture, and climate).

RESULTS

The results confirmed that the fertilizer application increased oat hay yield by 48.9% and grain yield by 36.2%. This study demonstrated that balanced fertilization with nitrogen, phosphorus, and potassium generally enhances oat hay and grain yield despite large temporal and spatial variations. Boosted regression tree (BRT) models suggest that changes in hay and grain yield were primarily dominated by soil pH and nitrogen fertilizer. The response ratio (the natural logarithm of the mean values of hay yield or grain yield with and without fertilization, respectively) of hay yield declined linearly with soil pH. Elevation was the second most important factor affecting the change in response ratio of hay yield and the third most important factor affecting the change in response ratio of grain yield but climatic conditions were not the dominant factors affecting changes in oat hay or grain yield.

CONCLUSION

Overall, these results will benefit producers considering site‐specific fertilization management of oat. They could increase yields and save investment in fertilizer, and help to facilitate the genetic breeding of oat varieties with high nutrient use efficiency. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Angioedema following venipuncture in a patient on angiotensin‐converting enzyme inhibitor and dipeptidyl peptidase‐IV inhibitor therapy: A case report
Authors: Bénic Adrien , Boyard Adrien , Pogossian Alexan , Misery Laurent , Roguedas‐Contios Anne‐Marie
Published: November 2024

Acquired angioedema (AAE) is a rare, potentially life‐threatening condition, primarily induced by medications, with attacks typically triggered by major trauma. We report a rare case of AAE triggered locally by minor trauma—a forearm venipuncture—in a 77‐year‐old male taking ramipril and sitagliptin. The venipuncture and these medications acted synergistically through distinct pathways in bradykinin metabolism, resulting in localized AAE. This case highlights the importance of recognizing minor trauma as a potential trigger in patients on multiple AAE‐inducing medications.
Inpatient cost comparison of total and unicompartmental knee arthroplasty in patients with medial compartmental osteoarthritis using time‐driven activity‐based costing
Authors: Lim Perry L. , Gonzalez Marcos R. , Goh Graham S. , Melnic Christopher M. , Bedair Hany S.
Published: November 2024

Purpose

Using time‐driven activity‐based costing (TDABC), we sought to compare the total facility costs, comprising supply and personnel costs during the episode of care for the index procedure, in patients with isolated medial compartmental knee osteoarthritis (OA) undergoing unicompartmental knee arthroplasty (UKA) versus total knee arthroplasty (TKA).

Methods

We conducted a retrospective analysis of 100 UKAs and 100 TKAs from 2019 to 2022. From a larger sample of 4899 TKAs and 137 UKAs, patients with isolated medial OA (Kellgren–Lawrence Grade <2 in other compartments) were radiographically identified. Demographic data included age, sex and body mass index, with comorbidities controlled using the Charlson comorbidity index. Facility costs were calculated using TDABC and standardized in cost units (CUs), a metric for comparing costs across procedures. Multiple regression analysis was used to assess the independent effect of TKA versus UKA on facility costs.

Results

TKA patients had similar operative times (TKA vs. UKA: 1.01×, p = 0.783) and supply costs (1.00×, p = 0.866), where ‘x’ denotes the relative cost ratio. However, TKA was associated with higher personnel costs (260.0 vs. 222.5 CUs [1.17×], p < 0.001) and total facility costs, both including (706.3 vs. 667.5 CUs [1.06×], p = 0.007) and excluding implants (353.8 vs. 312.5 CUs [1.13×], p < 0.001). Adjusted for demographics and comorbidities, TKA had increased facility costs, including (32.2 CUs, 95% confidence interval [CI]: 2.9–61.5, p = 0.031) and excluding implants (37.8 CUs, 95% CI: 15.2–60.3, p = 0.001).

Conclusions

TDABC analysis revealed higher total facility costs for the index procedure in TKA, suggesting UKA may be a cost‐saving alternative for isolated medial compartment knee OA.

Level of Evidence

Level III, retrospective comparative study.
Individualized post‐operative prediction of cochlear implantation outcomes in children with prelingual deafness using functional near‐infrared spectroscopy
Authors: Chen Zhe , Zhao Xue , Liu Haotian , Wang Yuyang , Zhang Zhikai , Zhang Yuxuan , Liu Yuhe
Published: November 2024

Objective

The goal of this study was to develop an objective measure and predictor of cochlear implantation (CI) outcomes using functional near‐infrared spectroscopy (fNIRS) for young children with prelingual deafness.

Methods

Sound‐evoked hemodynamic responses were recorded from auditory and language‐related cortical regions of 47 child CI recipients (35.47 ± 17.24 months of age) using fNIRS shortly after CI activation (0.26 ± 0.30 months). There were four sound conditions (natural speech, instrumental music, multi‐speaker babble noise, and speech‐in‐noise). Post‐CI auditory and verbal communication performance was evaluated using clinical questionnaires with caretakers. Both classification and individualized regression models were constructed to predict post‐CI behavioral improvement from fNIRS data using support vector machine (SVM) learning algorithms.

Results

Auditory cortical responses shortly after CI hearing onset yielded highly accurate prediction of behavioral development in young CI children. For classification models, optimal prediction was achieved using cortical responses to two or more sound conditions, with the highest accuracy of 98.20% (precision = 98.17%, sensitivity = 98.96%, area under the curve of the receiver operating characteristic curve = 99.61%) obtained with the combination of speech, noise, and music stimuli. Similarly, for regression models, best prediction of individual development was achieved using three (highest r = 0.919) or four (r = 0.966) sound conditions. The predictability of cortical responses far outperformed (Cohen's d: 18.56) that of the collection of audiological and demographic parameters (classification accuracy: 0.62) under the same SVM algorithms and could not benefit from the inclusion of the latter.

Conclusion

Machine learning models using auditory cortical hemodynamic responses shortly after CI activation were able to predict individualized post‐CI behavioral improvement in children with prelingual deafness.

Level of Evidence

Level 5.
Multi‐Color Optical Quasiparticle Laser Source Formed of a Pr3+ Doped Fiber Laser with a Dual‐Output Coupling Geometry
Authors: Yoneda Yuto , Allam Srinivasa Rao , Kerridge‐Johns William R. , Fujimoto Yasushi , Omatsu Takashige
Published: November 2024

The generation of multicolor (523, 605, 637, and 719 nm) optical quasiparticles (bimerons and skyrmions with topologically protected polarization textures) from a diode‐pumped Pr3+‐doped fluoro‐aluminate glass (Pr3+: WPFG) fiber simply with intra‐cavity plano‐convex lens and wedge‐plate and without any wavefront control elements, such as a spatial light modulator is demonstrated. This robust and cost‐saving system efficiently produces Bloch‐, Néel‐, and anti‐quasiparticles with high mode purity. In particular, the green optical quasiparticles will have the potential to explore many applications in materials science and biotechnologies.
Photo‐Accelerated Synthesis of Oligo(triazole amide)s
Authors: Petropoulos Alexandros , Charles Laurence , Becht Jean‐Michel , Schmitt Michael , Lalevée Jacques , Lutz Jean‐François
Published: November 2024

A photo‐assisted process is explored for improving the synthesis of oligo(triazole amide)s, which are prepared by solid phase synthesis using a repeated cycle of two reactions: amine‐carboxylic acid coupling and copper‐catalyzed azide‐alkyne cycloaddition (CuAAC). The improvement of the second reaction is investigated herein. A catalytic system involving Cu(II)Cl2, N,N,N’,N″,N″‐pentamethyldiethylenetriamine (PMDETA) and a titanocene photoinitiator is explored for reducing the reaction time of CuAAC. This catalyst is first tested on a model reaction involving phenylacetylene and ethyl azidoacetate in DMSO. The kinetics of these model experiments are monitored by 1H NMR in the presence of different concentrations of the photoinitiator. It is found that 30 mol% of photoinitiator leads to quantitative reactions in only 8 min. These conditions are then applied to the solid phase synthesis of oligo(triazole amide)s, performed on a glycine‐loaded Wang resin. The backbone of the oligomers is constructed using 6‐heptynoic acid and 1‐amino‐11‐azido‐3,6,9‐trioxaundecane as submonomers. Due to slow reagent diffusion, the CuAAC step required more time in the solid phase than in solution. Yet, one hour only is necessary to achieve quantitative CuAAC on the resin, which is twice as fast as previously‐reported conditions. Using these optimized conditions, oligo(triazole amide)s of different length are prepared.
Activated Phenyl Ester Vitrimers
Authors: Engelen Stéphanie , Daelman Bram , Winne Johan M. , Du Prez Filip E.
Published: November 2024

Aromatic esters are amongst the oldest known chemical motifs that allow for thermal (re)processing of thermosetting polymers. Moreover, phenyl esters are generally known as activated esters that do not require a catalyst to undergo acyl transfer reactions. Even though dynamic aromatic esters find applications in commercialized thermoset formulations, all‐aromatic esters have found limited use so far in the design of covalent adaptable networks (CAN) as a result of their high glass transition temperature (Tg) and specific curing process. Here, a strategy to include partly aromatic esters as dynamic cross‐links inside low Tg (−40 °C) thermosetting formulations, using aliphatic esters derived from para‐hydroxybenzoic acid, which serves as a highly activated phenol or as a reactive “phenylogous anhydride” is reported. A small molecule study shows that the activated phenyl ester bonds can readily exchange with free phenol moieties at 200 °C under catalyst‐free conditions, while the addition of a catalyst allows for a faster exchange. Robust and hydrophobic polymer networks are conveniently prepared via rapid thiol‐ene UV‐curing of unsaturated phenol esters. The obtained networks show high thermal stability (350 °C), fast processability, good water resistance, and low creep up to 120 °C, thus showing good promise as a platform for CAN.
Bubble‐Assisted Sample Preparation Techniques for Mass Spectrometry
Authors: Elpa Decibel P. , Urban Pawel L.
Published: November 2024

This review delves into the efficacy of utilizing bubbles to extract analytes into the gas phase, offering a faster and greener alternative to traditional sample preparation methods for mass spectrometry. Generating numerous bubbles in liquids rapidly transfers volatile and surface‐active species to the gas phase. Recently, effervescence has found application in chemical laboratories for swiftly extracting volatile organic compounds, facilitating instantaneous analysis. In the so‐called fizzy extraction, liquid matrices are pressurized with gas and then subjected to sudden decompression to induce effervescence. Alternatively, specifically designed effervescent tablets are introduced into the liquid samples. In situ bubble generation has also enhanced dispersion of extractant in microextraction techniques. Furthermore, droplets from bursting bubbles are collected to analyze non‐volatile species. Various methods exist to induce bubbling for sample preparation. The polydispersity of generated bubbles and the limited control of bubble size pose critical challenges in the stability of the bubble–liquid interface and the ability to quantify analytes using bubble‐based sample preparation techniques. This review covers different bubble‐assisted sample preparation methods and gives practical guidance on their implementation in mass spectrometry workflows. Traditional, offline, and online approaches for sample preparation relying on bubbles are discussed. Unconventional bubbling techniques for sample preparation are also covered.
The Effects of Carbonate on Candida albicans Filamentation, Biofilm Formation, and Antifungal Resistance
Authors: Miedema Trenton P. , Grooters Kayla E. , Cleary Ian A.
Published: November 2024

Candida albicans, a member of the normal microbial population of healthy humans, is an opportunistic pathogen that can cause serious disease in immunocompromised patients. An important virulence factor of C. albicans is the formation of biofilms. These organized communities of cells are efficient at attaching to host cells and implanted medical devices. Carbonate has been studied as an agricultural antifungal agent, and here we demonstrate that carbonate can affect filamentation, biofilm formation, and antifungal drug resistance in C. albicans.
The Genomic Landscape of Wilson Disease in a Pan India Disease Cohort and Population‐Scale Data
Authors: Kumar Mukesh , Sharma Srishti , Pandey Sanjay , Mammayil Geetha , Pala kuzhiyil Aslam , Sreesh Srijaya , Arakkal Riyaz , Radhakrishnan Divya M. , Rajan Roopa , Amalnath Deepak , Gulati Reena , Tayade Naresh , Sadasivan Shine , Valsan Arun , Menon Jagadeesh , Kamate Mahesh , Mathur Sandeep Kumar , Mahadevan Radha , Dhingra Bhavna , Rajan Rajneesh , Singh Kuldeep , Shalimar  , Geevarghese Suja K. , Kumar Vikram S. , Menachery John , Aliyar Aminu , Bhoyar Rahul C. , Jolly Bani , Jain Abhinav , Vittal Rangan Arvinden , Moitra Trisha , Mhaske Aditi , Gupta Vishu , Senthivel Vigneshwar , Mishra Anushree , Saini Arti , Gaharwar Utkarsh , Sivasubbu Sridhar , Scaria Vinod , B. K. Binukumar
Published: November 2024

Background

Wilson's disease (WD) results from pathogenic ATP7B gene variations, causing copper accumulation mainly in the liver, brain, and kidneys.

Objectives

In India, despite studies on ATP7B variants, WD often goes undiagnosed, with the prevalence, carrier rate, and mutation spectrum remaining unknown.

Methods

A multicenter study examined genetic variations in WD among individuals of Indian origin via whole exome sequencing. The study used the InDelible structural variants calling pipeline and conducted molecular dynamic simulations on variants of uncertain significance (VUS) in ATP7B AlphaFold protein structures. Additionally, a high‐throughput gene screening panel for WD was developed.

Results

This study examined 128 clinically diagnosed cases of WD, revealing 74 genetically confirmed cases, 22 with ATP7B variants, and 32 without. Twenty‐two novel ATP7B gene variants were identified, including a 322 bp deletion classified as a structural variant. Molecular dynamics simulations highlighted the potential deleterious effects of 11 ATP7B VUS. Gene burden analysis suggested associations with ANO8, LGR4, and CDC7. ATP7B gene hotspots for pathogenic variants were identified. Prevalence and carrier rates were determined as one in 18,678 and one in 67, respectively. A multiplex sequencing panel showed promise for accurate WD diagnosis.

Conclusions

This study offers crucial insights into WD's genetic variations and prevalence in India, addressing its underdiagnosis. It highlights the novel genetic variants in the ATP7B gene, the involvement of other genes, a scalable, cost‐effective multiplex sequencing panel for WD diagnosis and management and promising advancements in WD care.
Early Changes in the Locus Coeruleus in Mild Cognitive Impairment with Lewy Bodies
Authors: Železníková Žaneta , Nováková L'ubomíra , Vojtíšek Lubomír , Brabenec Luboš , Mitterová Kristína , Morávková Ivona , Rektorová Irena
Published: November 2024

Background

Although neuromelanin‐sensitive magnetic resonance imaging (NM‐MRI) has been used to evaluate early neurodegeneration in Parkinson's disease, studies concentrating on the locus coeruleus (LC) in pre‐dementia stages of dementia with Lewy bodies (DLB) are lacking.

Objectives

The aims were to evaluate NM‐MRI signal changes in the LC in patients with mild cognitive impairment with Lewy bodies (MCI‐LB) compared to healthy controls (HC) and to identify the cognitive correlates of the changes. We also aimed to test the hypothesis of a caudal‐rostral α‐synuclein pathology spread using NM‐MRI of the different LC subparts.

Methods

A total of 38 MCI‐LB patients and 59 HCs underwent clinical and cognitive testing and NM‐MRI of the LC. We calculated the contrast ratio of NM‐MRI signal (LC‐CR) in the whole LC as well as in its caudal, middle, and rostral MRI slices, and we compared the LC‐CR values between the MCI‐LB and HC groups. Linear regression analyses were performed to assess the relationship between the LC‐CR and cognitive outcomes.

Results

The MCI‐LB group exhibited a significant reduction in the right LC‐CR compared to HCs (P = 0.021). The right LC‐CR decrease was associated with impaired visuospatial memory in the MCI‐LB group. Only the caudal part of the LC exhibited significant LC‐CR decreases in MCI‐LB patients compared to HCs on both sides (P < 0.0001).

Conclusions

This is the first study that focuses on LC‐CRs in MCI‐LB patients and analyzes the LC subparts, offering new insights into the LC integrity alterations in the initial stages of DLB and their clinical correlates. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Small but mighty: Platelets as multifunctional architects of tumor metastasis and immune regulation
Authors: Tang Leyi , Shi Hubing , Luo Yong
Published: November 2024

Platelets play an irreplaceable role in hemostasis and wound healing. However, beyond these classical roles, as the smallest anucleate cells in the blood stream, they are crucial for immune response which have inflammatory functions through specialized receptors and different signaling pathways, influencing both innate and adaptive immune response. Furthermore, many research have proved that platelets significantly contribute to tumor metastasis and are associated with poor prognoses in cancer patients through its coagulability and supporting an immunosuppressive tumor microenvironment. When tumor cells detach from the primary tumor mass and enter the bloodstream, they rapidly initiate the direct activation and adhesion of platelets, forming a protective microenvironment. This environment shields circulating tumor cells (CTCs) from the mechanical shear forces of blood flow and immune surveillance. Here we delve into the interaction between platelets and immunomodulation and explore the multifaceted roles and underlying mechanisms by which platelets influence tumor cell metastasis and tumor growth. Furthermore, we also discussed the diagnostic role of platelets in cancer occurrence and progression, as well as the feasibility and prospects of targeting platelets for antitumor immunotherapy. This review provides a multidimensional perspective and reference for platelet‐related cancer treatment strategies and diagnosis.
Radiomics‐guided generative adversarial network for automatic primary target volume segmentation for nasopharyngeal carcinoma using computed tomography images
Authors: Jin Juebin , Zhang Jicheng , Yu Xianwen , Xiang Ziqing , Zhu Xuanxuan , Guo Mingrou , Zhao Zeshuo , Li WenLong , Li Heng , Xu Jiayi , Jin Xiance
Published: November 2024

Background

Automatic primary gross tumor volume (GTVp) segmentation for nasopharyngeal carcinoma (NPC) is a quite challenging task because of the existence of similar visual characteristics between tumors and their surroundings, especially on computed tomography (CT) images with severe low contrast resolution. Therefore, most recently proposed methods based on radiomics or deep learning (DL) is difficult to achieve good results on CT datasets.

Purpose

A peritumoral radiomics‐guided generative adversarial network (PRG‐GAN) was proposed to address this challenge.

Methods

A total of 157 NPC patients with CT images was collected and divided into training, validation, and testing cohorts of 108, 9, and 30 patients, respectively. The proposed model was based on a standard GAN consisting of a generator network and a discriminator network. Morphological dilation on the initial segmentation results from GAN was first conducted to delineate annular peritumoral region, in which radiomics features were extracted as priori guide knowledge. Then, radiomics features were fused with semantic features by the discriminator's fully connected layer to achieve the voxel‐level classification and segmentation. The dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and average symmetric surface distance (ASSD) were used to evaluate the segmentation performance using a paired samples t‐test with Bonferroni correction and Cohen's d (d) effect sizes. A two‐sided p‐value of less than 0.05 was considered statistically significant.

Results

The model‐generated predictions had a high overlap ratio with the ground truth. The average DSC, HD95, and ASSD were significantly improved from 0.80 ± 0.12, 4.65 ± 4.71  mm, and 1.35 ± 1.15  mm of GAN to 0.85 ± 0.18 (p = 0.001, d = 0.71), 4.15 ± 7.56 mm (p = 0.002, d = 0.67), and 1.11 ± 1.65 mm (p < 0.001, d = 0.46) of PRG‐GAN, respectively.

Conclusion

Integrating radiomics features into GAN is promising to solve unclear border limitations and increase the delineation accuracy of GTVp for patients with NPC.
Orientation‐independent quantification of macromolecular proton fraction in tissues with suppression of residual dipolar coupling
Authors: Gao Zijian , Yu Ziqiang , Zhou Ziqin , Hou Jian , Jiang Baiyan , Ong Michael , Chen Weitian
Published: November 2024

Quantitative magnetization transfer (MT) imaging enables noninvasive characterization of the macromolecular environment of tissues. However, recent work has highlighted that the quantification of MT parameters using saturation radiofrequency (RF) pulses exhibits orientation dependence in ordered tissue structures, potentially confounding its clinical applications. Notably, in tissues with ordered structures, such as articular cartilage and myelin, the residual dipolar coupling (RDC) effect can arise owing to incomplete averaging of dipolar–dipolar interactions of water protons. In this study, we demonstrated the confounding effect of RDC on quantitative MT imaging in ordered tissues can be suppressed by using an emerging technique known as macromolecular proton fraction mapping based on spin‐lock (MPF‐SL). The off‐resonance spin‐lock RF pulse in MPF‐SL could be designed to generate a strong effective spin‐lock field to suppress RDC without violating the specific absorption rate and hardware limitations in clinical scans. Furthermore, suppressing the water pool contribution in MPF‐SL enabled the application of a strong effective spin‐lock field without confounding effects from direct water saturation. Our findings were experimentally validated using human knee specimens and healthy human cartilage. The results demonstrated that MPF‐SL exhibits lower sensitivity to tissue orientation compared with ,, and saturation‐pulse‐based MT imaging. Consequently, MPF‐SL could serve as a valuable orientation‐independent technique for the quantification of MPF.
Motion and magnetic field inhomogeneity correction techniques for chemical exchange saturation transfer (CEST) MRI: A contemporary review
Authors: Simegn Gizeaddis Lamesgin , Sun Phillip Zhe , Zhou Jinyuan , Kim Mina , Reddy Ravinder , Zu Zhongliang , Zaiss Moritz , Yadav Nirbhay Narayan , Edden Richard A. E. , van Zijl Peter C. M. , Knutsson Linda
Published: November 2024

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as a powerful imaging technique sensitive to tissue molecular composition, pH, and metabolic processes in situ. CEST MRI uniquely probes the physical exchange of protons between water and specific molecules within tissues, providing a window into physiological phenomena that remain invisible to standard MRI. However, given the very low concentration (millimolar range) of CEST compounds, the effects measured are generally only on the order of a few percent of the water signal. Consequently, a few critical challenges, including correction of motion artifacts and magnetic field (B0 and B1+) inhomogeneities, have to be addressed in order to unlock the full potential of CEST MRI. Motion, whether from patient movement or inherent physiological pulsations, can distort the CEST signal, hindering accurate quantification. B0 and B1+ inhomogeneities, arising from scanner hardware imperfections, further complicate data interpretation by introducing spurious variations in the signal intensity. Without proper correction of these confounding factors, reliable analysis and clinical translation of CEST MRI remain challenging. Motion correction methods aim to compensate for patient movement during (prospective) or after (retrospective) image acquisition, reducing artifacts and preserving data quality. Similarly, B0 and B1+ inhomogeneity correction techniques enhance the spatial and spectral accuracy of CEST MRI. This paper aims to provide a comprehensive review of the current landscape of motion and magnetic field inhomogeneity correction methods in CEST MRI. The methods discussed apply to saturation transfer (ST) MRI in general, including semisolid magnetization transfer contrast (MTC) and relayed nuclear Overhauser enhancement (rNOE) studies.
From Corporate Artification to Artification in the Third Sector
Authors: Turrini Alex , Massi Marta , Piancatelli Chiara
Published: November 2024

Artification refers to the process by which objects, practices, or entities not traditionally considered art are transformed into socially accepted art forms. A common example is graffiti, which was once regarded as vandalism but has since evolved into a recognized and celebrated form of art, but organizations and brands can also engage in artification strategies. This special issue of the Journal of Philanthropy and Marketing explores the concept of artification, with a particular focus on its application within the third sector. The six papers in this issue examine how artification fosters creativity, innovation, and social impact in non‐profits. Through case studies and empirical research, the issue demonstrates how third‐sector organizations, such as arts and culture institutions, charities, and foundations, can leverage artification not only to support the arts but also to enhance their legitimacy, build stronger community relationships, and increase credibility with stakeholders. The special issue examines studies on artification in both non‐profit organizations and corporate initiatives, emphasizing how art fosters social sustainability through creative partnerships. Collectively, these papers underscore the transformative potential of artification in the third sector, offering valuable insights for non‐profits seeking to integrate art into their strategic initiatives and enhance their social impact.
The Stepwise Artification Process in Luxury Fashion: Strategic Integration With the Arts and Collaboration With Non‐Profit Institutions
Authors: Mion Dalle Carbonare Piergiacomo , Luchetti Marco , Rurale Andrea , Fanin Elisa
Published: November 2024

This article investigates the diverse artification strategies used by luxury fashion brands to strengthen their connection with the art world and emphasises how these strategies infuse objects, practices, and brands with artistic value. Using a theoretical framework, the research classifies the Altagamma and Comité Colbert brands into distinct clusters representing various stages of the artification process, from early exploration to full integration of artistic practices. The study analyses the ways in which these stages reflect the brands’ historical evolution and strategic investments in artification, particularly in response to market threats. Between 2019 and 2024, 81.25% of the 39 brands examined in this study engaged in at least one artistic activity, such as artist collaborations, art installations or incorporating artistic elements into collections. This study offers new insights by expanding the understanding of artification and classifying underexplored connections between luxury brands, artists and non‐profit cultural institutions. It reveals how brands, despite differing approaches, recognise artification as a key strategy in enhancing identity and positioning in the luxury market.
Experimental and numerical studies of the open hole tensile strength of drilled‐ and molded‐hole unidirectional laminates
Authors: Liu Dongxu , Zhao Shicai , Zhang Deyuan
Published: November 2024

In this paper, we created a new molded‐hole process to manufacture holes instead of drilling in unidirectional (UD) carbon fiber reinforced plastics avoid fiber discontinuity. Several open hole tensile (OHT) tests were carried out on specimens with Cross ply (CP) and Quasi‐isotropic (QI) stacking sequence with drilled holes and molded holes. At the same time, we established finite element analysis (FEA) models of drilled‐hole laminate and molded‐hole laminate to characterize the stress field around the hole. The numerical analysis results reveals that the max principal strain distribution around the molded hole has much higher coincidence with fiber axial direction than that in drilled‐hole laminate. Moreover, the OHT strength results of QI specimens indicate that the plates with molded holes were more 50% higher than those with drilled holes. This process will provide reference for molded UD CFRP structure holes. And the numerical model can help engineering designer make OHT strength prediction.

Highlights

A new molded‐hole process for unidirectional prepreg was created.

Molded‐hole specimens have higher open hole tensile strength than drilled‐hole pieces.

The simulation results were close to the experimental results.
Novel Nordaucane Sesquiterpenoid and Sesquiterpene Lactone From Laserpitium Species: Isolation, Structure Elucidation, In Vitro, In Vivo, and In Silico Evaluation as Anticancer Agents
Authors: Güleç Meltem , Şenol Halil , Tan Nur
Published: November 2024

Introduction

This study explores the cytotoxic activity‐guided isolation of the underground parts of Laserpitium hispidum M. Bieb and Laserpitium petrophilum Boiss. & Heldr., which have not been previously investigated.

Objectives

The aim is to isolate and evaluate bioactive compounds from Laserpitium L. species with anticancer potential.

Material and Methods

This study involves bioactivity‐guided isolation and structural studies of the pure compounds utilizing NMR, UV–Vis, IR spectroscopies, and HRMS. The cytotoxic activity of the isolated compounds was evaluated in vitro and in vivo, whereas molecular modeling, docking, and ADME predictions were conducted using Schrödinger software.

Results

The study isolated phenylpropanoids (laserine (1), latifolone (2), myristicin (3)), sterol (stigmasterol (4)), polyenes (falcarindiol (5)), sesquiterpene lactone (11‐hydroxybadkhyzin (6)), and nordaucane sesquiterpene (norlasidiol angelate (7)) from L. hispidum, whereas L. petrophilum yielded 10β‐acetoxy‐8α‐angeloyloxy‐6αH,7αH‐guaian‐3‐en‐12,6‐olide (8), 10β‐acetoxy‐8α‐senecioyloxy‐6αH,7αH‐guaian‐3‐en‐6,12‐olide (9) and acetylisomontanolide (10). Molecular docking simulations revealed stable interactions between compounds 7 and 9 with estrogen receptor α (ERα) and vascular endothelial growth factor receptor 2 (VEGFR2), with compound 7 showing superior stability and binding affinity. In silico ADME predictions indicated favorable pharmacokinetic properties, including high oral absorption.

Conclusion

Compounds 7 and 9, representing new nordaucane and sesquiterpene lactones, have not been previously reported. In vitro cytotoxicity revealed that compound 7 exhibits potent anti‐cancer activity against MCF‐7 cells, whereas compound 9 showed reduced cytotoxicity. In vivo testing in Caenorhabditis elegans supported these findings, suggesting safety and efficacy in organisms. In silico results emphasize the potential of these compounds, with compound 7 promising due to its stability and strong binding affinity.
Standardised and Reproducible Phenotyping Using Distributed Analytics and Tools in the Data Analysis and Real World Interrogation Network (DARWIN EU)
Authors: Dernie Francesco , Corby George , Robinson Abigail , Bezer James , Mercade‐Besora Nuria , Griffier Romain , Verdy Guillaume , Leis Angela , Ramirez‐Anguita Juan Manuel , Mayer Miguel A. , Brash James T. , Seager Sarah , Parry Rowan , Jodicke Annika , Duarte‐Salles Talita , Rijnbeek Peter R. , Verhamme Katia , Pacurariu Alexandra , Morales Daniel , Pinheiro Luis , Prieto‐Alhambra Daniel , Prats‐Uribe Albert
Published: November 2024

Purpose

The generation of representative disease phenotypes is important for ensuring the reliability of the findings of observational studies. The aim of this manuscript is to outline a reproducible framework for reliable and traceable phenotype generation based on real world data for use in the Data Analysis and Real‐World Interrogation Network (DARWIN EU). We illustrate the use of this framework by generating phenotypes for two diseases: pancreatic cancer and systemic lupus erythematosus (SLE).

Methods

The phenotyping process involves a 14‐steps process based on a standard operating procedure co‐created by the DARWIN EU Coordination Centre in collaboration with the European Medicines Agency. A number of bespoke R packages were utilised to generate and review codelists for two phenotypes based on real world data mapped to the OMOP Common Data Model.

Results

Codelists were generated for both pancreatic cancer and SLE, and cohorts were generated in six OMOP‐mapped databases. Diagnostic checks were performed, which showed these cohorts had broadly similar incidence and prevalence figures to previously published literature, despite significant inter‐database variability. Co‐occurrent symptoms, conditions, and medication use were in keeping with pre‐specified clinical descriptions based on previous knowledge.

Conclusions

Our detailed phenotyping process makes use of bespoke tools and allows for comprehensive codelist generation and review, as well as large‐scale exploration of the characteristics of the resulting cohorts. Wider use of structured and reproducible phenotyping methods will be important in ensuring the reliability of observational studies for regulatory purposes.
Real‐World Evidence of Indapamide‐Induced Rhabdomyolysis: A Retrospective Analysis of Electronic Health Records
Authors: Alroba Raseel , Alfakhri Almaha , Badreldin Hisham , Alrwisan Adel , Almadani Ohoud
Published: November 2024

Purpose

Previous research and pharmacovigilance monitoring activities have suggested a potential association between indapamide use and rhabdomyolysis. This study aims to investigate the potential causal relationship between the use of indapamide and rhabdomyolysis.

Methods

A case–control study conducted using electronic health records data, between July 1, 2016 and December 31, 2022. Patients who have rhabdomyolysis event (cases) were matched to four controls bases on age, gender, and date. We examined the odds for indapamide exposure through three risk periods: current use, recent use, and former. The study outcome was ascertained through the presence of CK level over 1000 U/L (i.e., rhabdomyolysis event). Subsequently, a multivariable conditional logistic regression analysis was utilized to assess the causal association of indapamide exposure on the likelihood of developing rhabdomyolysis, while accounting for potential confounding variables.

Results

The study population consisted of 2965 cases and 11 860 controls. The results of the conditional logistic regression analysis indicated a lack of association between exposure to indapamide for the current users with an odds ratio (OR) of 0.6 (95% confidence intervals (CI): 0.39–1.05). The odds of recent indapamide use among cases was lower than controls (OR 0.2; 95% CI: 0.14–0.47). Lastly, the OR for former use of indapamide was 0.1 (95% CI: 0.07–0.23).

Conclusions

In this study, we did not find association between indapamide use and rhabdomyolysis regardless timing of exposure.