bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL‐4/IL‐13 pathway in nasal type 2 inflammation: The central role and targeted therapy
Authors: Zhu Zhiqiu , Zhao Chaoran , Wang Ming 
Published: January 2024

AbstractType 2 dominant inflammation in nasal mucosa is the key underlying pathophysiological mechanism of allergic rhinitis (AR) and most presentations of chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin‐4 (IL‐4) and IL‐13 share common receptor subunits and signaling molecules, which lead to various pathological changes in different cells, playing key roles in the pathogenesis of nasal type 2 inflammation. Numerous clinical trials have shown that biologics targeting key molecules of the IL‐4/IL‐13 pathway, especially IL‐4 receptor alpha, can treat CRSwNP and AR with high efficacy, and are generally well tolerated. Several biologics have been approved for the treatment of difficult‐to‐control CRSwNP, while others also show promising results. Here, we review the IL‐4/IL‐13 pathway, its role in nasal type 2 inflammation, and current targeted therapies related to the IL‐4/IL‐13 pathway, with a focus on AR and CRSwNP.
Chitosan‐Based Nanogels Containing Ln3+ Chelates (Ln=Gd, Dy) as T1 and T2 MRI Probes
Authors: Ricci Marco , Carniato Fabio , Tei Lorenzo , Camorali Sara , Ferrauto Giuseppe , Botta Mauro 
Published: January 2024

AbstractNovel nanogels, characterized by high stability and incorporating macrocyclic chelates of Gd(III) and Dy(III), were synthesized and assessed for their effectiveness as T1 and T2 relaxation agents, respectively. In this specific design, we employed octacoordinated bifunctional Gd‐1,7‐DOTAGA2 chelate to cross‐link chitosan chains. The results revealed that the sample exhibited a relaxivity value at clinical magnetic field strengths (1.5 T), approximately seven times higher than that of currently available clinical contrast agents and good MRI contrast efficacy at both 7.1 and 1 T. Furthermore, the nanogel displayed excellent stability in biological fluids, with no discernible interactions with serum biomolecules and no release of metal. In addition to Gd(III)‐based probes commonly used as T1 positive contrast agents, the nanogel with the corresponding Dy‐1,7‐DOTAGA2 chelate was prepared to explore its potential as a T2 MRI probe. Dy‐based nanogel demonstrated notably elevated transverse relaxivity values compared to the free chelate at high magnetic fields (>3 T) and significant T2 MRI contrast at 7.1 T, a capability often lacking when employing an equivalent concentration of a low‐molecular‐weight Dy(III) complex. The characterization of paramagnetic complexes was completed through the measurement of 1H NMRD profiles and 17O NMR data.
Lanthanide Amide Complexes Supported by the Bis‐tris(pyrazolyl)borate Ligand Environment
Authors: Chowdhury Tajrian , Wilson Claire , Maichle‐Mössmer Cäcilia , Anwander Reiner , Farnaby Joy H. 
Published: January 2024

AbstractSynthesis of primary lanthanide amides in the bis‐hydrotris(1‐pyrazolyl)borate ligand environment has been achieved. Salt metathesis of [Dy(Tp)2(OTf)] 1‐Dy (OTf=CF3SO3) with K(N′′) (N′′=N(SiMe3)2) in toluene yielded the [bis(silyl)]amide [Dy(Tp)2(N′′)] 2‐Dy. Complexes 1‐Ln and 2‐Ln were both used to access primary lanthanide amides, where either metathesis of 1‐Ln with K(NHArCF3) (ArCF3=C6H3(CF3)2‐3,5) or protonolysis of 2‐Ln with H2NArCF3 in toluene yielded [Ln(Tp)2(NHArCF3)] 3‐Ln (Ln=Y, Dy). The synthesis of parent amides was also attempted, but the metathesis of 1‐Y with NaNH2 yielded complicated reaction mixtures, but from which the dimeric parent amide [{Y(Tp)2(μ‐NH2)}2] 4‐Y and an ‘ate’‐salt [{Y(Tp)2(μ2‐OTf)(μ3‐OTf)Na(THF)2}2] 5‐Y were isolated. Full characterisation data are presented for all complexes, including the structure determination.
On the Keto‐Enol‐Tautomerism of 2‐(1‐Hydroxyethylidene)malononitrile and Its Lewis Adduct Formation with B(C6F5)3
Authors: Surkau Jonas , Bresien Jonas , Michalik Dirk , Rohregger Mara Elén , Villinger Alexander , Schulz Axel 
Published: January 2024

Abstract2‐(1‐Hydroxyethylidene)malononitrile (4) is commercially sold as the keto isomer and is described in the literature as either a keto (4 b) or enol (4 a) species. Using NMR techniques and single crystal X‐ray diffraction, we were able to show that 4 exists exclusively as the enol isomer (4 a) in solution as well as in the solid state, which agrees with quantum chemical calculations. By adding one or two equivalents of the Lewis acid B(C6F5)3, the mono‐ or diadducts are formed in exergonic reactions, in which the enol form is further thermodynamically stabilized. The structure and acidity of enol 4 a and its borane adducts are discussed based on experimental and theoretical results.
Impact of cryogenic treatment on the performance of coated tungsten carbide inserts during machining of EN24 grade alloy steel
Authors: Prem Chand R. , Reddy T. V. Sreerama , Anjinappa Chandrashekar , Omprakash B. , Razak Abdul , Wodajo Anteneh Wogasso 
Published: January 2024

AbstractToday's industries need to be more productive, especially those that shape and machine materials. As a result, engineers and scientists are seeking for cutting tool materials and technologies that have high hot hardness, chemical stability, wear resistance, and toughness while also improving tool life or contact time. Cryogenic treatment of cutting tools has been proven to be a good way for increasing the contact time of any cutting tool material. This study presents the results of turning alloy steel (EN24 grade) using P20 grade carbide inserts under various conditions under continuous machining. Cutting speeds varied from 100 to 500 m/min (in increments of 100 m/min), with feed rates ranging from 0.1 to 0.4 mm/rev in stages of 0.1 mm/rev and a constant radial depth of cut of 1.5 mm were considered under dry machining conditions. Cryogenic treated/coated inserts are better than other inserts in terms of tool life for optimized parameters such as cutting speed 100 m/min, feed rate 0.1 mm/rev, and depth of cut 1.5 mm, according to the study's findings. Under similar conditions of cutting speed, feed rate, and depth of cut, coated/cryotreated inserts had a tool life increase of about 97.5% over uncoated/untreated inserts, a 50.58% increase over uncoated/crytreated inserts, and a 23.89% increase over coated and untreated inserts, respectively.
The evaluation of L‐arginine solution as a solvent for propolis extraction: The phenolic profile, antioxidant, antibacterial activity, and in vitro bioaccessibility
Authors: Mergen Duymaz Gizem , Duz Gamze , Ozkan Kubra , Karadag Ayse , Yilmaz Ozlem , Karakus Ayca , Cengiz Ozlem , Akyildiz Ismail Emir , Basdogan Gunay , Damarlı Emel , Sagdic Osman 
Published: January 2024

AbstractEthanol has been widely used for the extraction of propolis. Due to its certain disadvantages, there has been an ongoing search to find alternative non‐ethanolic extraction solvents. This study aimed to compare the phenolics, antioxidant, and antibacterial activity of propolis extracts prepared with 70% ethanol (EWE), propylene glycol (PGE), and L‐arginine solution (BE). All extracts were subjected to an in vitro simulated digestion procedure, and the phenolic profile of non‐digested and digested samples was determined by using LC–MS/MS. Additionally, the change in total phenolic (TPC), total flavonoid content (TFC), and antioxidant capacities were determined at each digestion phase. TPC and TFC of non‐digested propolis extracts had similar values, although BE showed higher antioxidant capacity (p < .05). The amount of TPC reached or transformed at the intestinal stage was higher for BE and PG compared to EWE. BE also provided the highest antioxidant capacity assay in digested samples. The most common phenolics were pinocembrin, pinobanskin, galangin, and CAPE in non‐digested extracts. However, their concentration was drastically reduced by digestion, and their recovery (R%) ranged from 0% to 9.38% of the initial amount detected in the non‐digested extracts. Chrysin was the most bioaccessible flavonoid in all extracts. Among phenolic acids, the highest R% was determined for trans‐cinnamic acid (22.14%) from BE. All extracts showed in vitro inhibitory activity against Escherichia coli and Staphylococcus aureus. This study suggests that an L‐arginine solution could be used as an alternative solvent to ethanol and propylene glycol for propolis extraction.
Cognition and motion dysfunction‐associated brain functional network disruption in diabetic peripheral neuropathy
Authors: Xin Haotian , Fu Yajie , Wen Hongwei , Feng Mengmeng , Sui Chaofan , Gao Yian , Guo Lingfei , Liang Changhu 
Published: January 2024

AbstractNeuroimaging studies have demonstrated extensive brain functional alterations in cognitive and motor functional areas in Type 2 diabetes mellitus (T2DM) with diabetic peripheral neuropathy (DPN), suggesting potential alterations in large‐scale brain networks related to DPN and associated cognition and motor dysfunction. In this study, using resting‐state functional connectivity (FC) and graph theory computational approaches, we investigated the topological disruptions of brain functional networks in 28 DPN, 43 T2DM without DPN (NDPN), and 32 healthy controls (HCs) and examined the correlations between altered network topological metrics and cognitive/motor function parameters in T2DM. For global topology, NDPN exhibited a significantly decreased shortest path length compared with HCs, suggesting increased efficient global integration. For regional topology, DPN and NDPN had separated topological reorganization of functional hubs compared with HCs. In addition, DPN showed significantly decreased nodal efficiency (Enodal), mainly in the bilateral superior occipital gyrus (SOG), right cuneus, middle temporal gyrus (MTG), and left inferior parietal gyrus (IPL), compared with NDPN, whereas NDPN showed significantly increased Enodal compared with HCs. Intriguingly, in T2DM patients, the Enodal of the right SOG was significantly negatively correlated with Toronto Clinical Scoring System scores, while the Enodal of the right postcentral gyrus (PoCG) and MTG were significantly positively correlated with Montreal Cognitive Assessment scores. Conclusively, DPN and NDPN patients had segregated disruptions in the brain functional network, which were related to cognition and motion dysfunctions. Our findings provide a theoretical basis for understanding the neurophysiological mechanism of DPN and its effective prevention and treatment in T2DM.
Distinct parallel activation and interaction between dorsal and ventral pathways during phonological and semantic processing: A cTBS‐fMRI study
Authors: Luo Yudan , Wang Ke , Jiao Saiyi , Zeng Jiahong , Han Zaizhu 
Published: January 2024

AbstractSuccessful visual word recognition requires the integration of phonological and semantic information, which is supported by the dorsal and ventral pathways in the brain. However, the functional specialization or interaction of these pathways during phonological and semantic processing remains unclear. Previous research has been limited by its dependence on correlational functional magnetic resonance imaging (fMRI) results or causal validation using patient populations, which are susceptible to confounds such as plasticity and lesion characteristics. To address this, the present study employed continuous theta‐burst stimulation combined with fMRI in a within‐subject design to assess rapid adaptation in regional activity and functional connectivity of the dorsal and ventral pathways during phonological and semantic tasks. This assessment followed the precise inhibition of the left inferior parietal lobule and anterior temporal lobe in the dorsal and ventral pathways, respectively. Our results reveal that both the dorsal and ventral pathways were activated during phonological and semantic processing, while the adaptation activation and interactive network were modulated by the task type and inhibited region. The two pathways exhibited interconnectivity in phonological processing, and disruption of either pathway led to rapid adaptation across both pathways. In contrast, only the ventral pathway exhibited connectivity in semantic processing, and disruption of this pathway alone resulted in adaptive effects primarily in the ventral pathway. These findings provide essential evidence supporting the interactive theory, phonological information processing in particular, potentially providing meaningful implications for clinical populations.
Treatment of nasolabial fold rhabdomyosarcoma in children: A single‐institution experience
Authors: Zhang Ge , Sun Nian , Ni Xin , Su Yan , He Lejian , Liu Zhikai , Zhang Jie , Li Yanzhen , Zhang Xuexi , Liu Qiaoyin , Liu Zhiyong , Li Xiaodan , Mei Lin , Liu Yuwei , Ji Tingting , Wang Shengcai 
Published: January 2024

AbstractObjectivesTo summarize the clinical characteristics and prognosis of children with nasolabial fold rhabdomyosarcoma (RMS).MethodsRetrospective review of children treated for nasolabial fold RMS from January 2014 to September 2019.ResultsOf 21 patients with nasolabial fold RMS, 90.48% were alveolar subtype, in which PAX3/7‐FOXO1 fusion positive accounted for 87.5%. Ten patients (47.62%) had nodals invasion. Almost all patients received comprehensive treatment (chemotherapy [100%], radiation therapy [100%], and surgery [95.24%]). The median follow‐up time was 34.3 months. The 3‐year overall survival (OS) and event‐free survival (EFS) was 67.7% ± 14.1% and 42.1% ± 13.5%, respectively. Four patients had regional lymph node relapse (NR), all in the ipsilateral submandibular lymph node region.ConclusionMajority of the patients with RMS in the nasolabial fold area were alveolar subtype and had positive PAX3/7‐FOXO1 gene fusion. In addition, the nasolabial fold RMS had a high probability of regional lymph node metastasis in the submandibular area. To maintain the facial aesthetics and functions, the surgical area for nasolabial fold RMS is often very conservative and restricted. This could be one of the contributors for the poor prognosis of nasolabial fold RMS beside its worse pathological subtype and gene fusion.
Decision support system based on a hybrid genetic algorithm–Kohonen map for combined mode conduction–radiation heat transfer in a porous medium: A comparative assessment of three variations of the Kohonen map
Authors: Ansari MD Mumtaz A. , Mishra Vijay K. , Sahu Kunja B. , Chaudhuri Sumanta , Ghose Prakash , Kar Vishesh Ranjan 
Published: January 2024

AbstractA hybrid genetic algorithm (GA)–Kohonen map, with its three variants, is explored for the first time for the decision‐making system in a porous ceramic matrix (PCM)‐based burner through determination of the regime of operation. Four different attributes of PCMs such as convective coupling (P2), extinction coefficient (β), downstream porosity (ϕ2), and scattering albedo (ω) are selected for determining the regime of operation of a PCM‐based burner. Changes in any of these attributes of a PCM lead to significant changes in the temperature profiles of the gas and solid phases. Temperature profiles of the gas and solid phases are computed by developing a numerical model. Various samples corresponding to different regimes are generated and used in a hybrid GA–Kohonen map. The best architectural details such as the neuron number and training epochs are obtained from GA as output. The best Kohonen map is trained with the input data, and regimes of operation for new temperature profiles are predicted. A supervised Kohonen map is able to provide the highest average class prediction of more than 40%. All the variants are assessed under two different types of neuron grids: hexagonal and rectangular. Comparative assessments of the three different variants of Kohonen maps, in terms of CPU time and average class prediction, are carried out.
Opioid analgesics prescribing trends 2010–2019 in Slovenia: National database study
Authors: Cebron Lipovec Nanca 
Published: January 2024

AbstractObjectiveSignificant increases in global opioid use have been reported in recent decades. This study analyzed opioid utilization in outpatient care in Slovenia between 2010 and 2019.MethodsThis retrospective cross‐sectional study performed a nationwide database analysis of all outpatient opioid analgesic prescriptions based on Slovenian health insurance claims data. Prevalence was defined as the number of recipients prescribed at least one opioid per 1000 inhabitants. Opioid consumption was presented as the total number of dispensed prescriptions per 1000 inhabitants and dispensed defined daily doses (DDD) per 1000 inhabitants for each year analyzed.ResultsThe age‐standardized prevalence of opioid recipients decreased by 21.5% during the study period. Total opioid consumption decreased both in the number of prescriptions (−9.2%) and DDD (−5.4%). Tramadol consumption decreased in terms of the number of prescriptions (−12.2%) and DDD (−2.7%), whereas prescriptions for strong opioids increased (10.2%) and DDDs decreased (−16.2%). The results suggest less intensive prescribing of strong opioids and more intensive prescribing for tramadol. The most frequently used strong opioids were fentanyl and oxycodone/naloxone.ConclusionsThe prevalence of opioid recipients and opioid consumption is decreasing in Slovenia. Further research is needed to understand whether this finding reflects safe use or underuse of these important analgesics.
In vivo deep brain multiphoton fluorescence imaging emitting at NIR‐I and NIR‐II and excited at NIR‐IV
Authors: Zhong Jincheng , Zhang Yingxian , Chen Xinlin , Tong Shen , Deng Xiangquan , Huang Jie , Li Zhenhui , Zhang Chi , Gao Zhiang , Li Jia , Qiu Ping , Wang Ke 
Published: January 2024

AbstractMultiphoton microscopy (MPM) enables deep brain imaging. Three optical windows: NIR‐I, NIR‐II, and NIR‐III are widely used. Recently, NIR‐IV (the 2200 nm window) has been demonstrated to be the last and longest window for deep tissue MPM. However, so far MPM covers only two optical windows labeled by single fluorescent probe, one for emission and one for excitation. Here we demonstrate in vivo deep brain MPM covering three optical windows, with emission at NIR‐I, NIR‐II, and excitation at NIR‐IV, labeled by ICG. The innovations include: (1) characterizing both 3‐photon excitation and emission properties of ICG emitting at both NIR‐I and NIR‐II, in water, plasma, and circulating blood; (2) a home‐built multiphoton microscope with simultaneous dual channel detection, with which we demonstrate deep brain MPM 950 μm (NIR‐I) and 850 μm (NIR‐II) into the mouse brain in vivo, verifying that multi‐optical window MPM is promising for deep brain imaging.
Nonsynonymous mutations in VEGF receptor binding domain alter the efficacy of bevacizumab treatment
Authors: Ahamed Ashif , Samanta Arijit , Alam Syed Sahajada Mahafujul , Mir Showkat Ahmad , Jamil Zarnain , Ali Safdar , Hoque Mehboob 
Published: January 2024

AbstractVascular endothelial growth factor (VEGF) mediated angiogenesis is crucial for tumor progression. Isoforms of VEGF bind to different VEGF receptors (VEGFRs) to initiate angiogenesis specific cellular signaling. Inhibitors that target both the receptors and ligands are in clinical use to impede angiogenesis. Bevacizumab, a monoclonal antibody (mAb) approved by the Food and Drug Administration (FDA), binds in the VEGF receptor binding domain (RBD) of all soluble isoforms of VEGF and inhibits the VEGF‐VEGFR interaction. Bevacizumab is also used in combination with other chemotherapeutic agents for a better therapeutic outcome. Understanding the intricate polymorphic character of VEGFA gene and the influence of missense or nonsynonymous mutations in the form of nonsynonymous polymorphisms (nsSNPs) on RBD of VEGF may aid in increasing the efficacy of this drug. This study has identified 18 potential nsSNPs in VEGFA gene that affect the VEGF RBD structure and alter its binding pattern to bevacizumab. The mutated RBDs, modeled using trRosetta, in addition to the changed pattern of secondary structure, post translational modification and stability compared to the wild type, have shown contrasting binding affinity and molecular interaction pattern with bevacizumab. Molecular docking analysis by ClusPro and visualization using PyMol and PDBsum tools have detected 17 nsSNPs with decreased binding affinity to bevacizumab and therefore may impact the treatment efficacy. Whereas VEGF RBD expressed due to rs1267535717 (R229H) nsSNP of VEGFA has increased affinity to the mAb. This study suggests that genetic characterization of VEGFA before bevacizumab mediated cancer treatment is essential in predicting the appropriate efficacy of the drug, as the treatment efficiency may vary at individual level.
Augmented mitochondrial apoptotic signaling impairs C2C12 myoblast differentiation following cellular aging through sequential passaging
Authors: Rahman Fasih A. , Hian‐Cheong Dylan J. , Boonstra Kristen , Ma Andrew , Thoms James P. , Zago Anderson S. , Quadrilatero Joe 
Published: January 2024

AbstractAging is associated with the steady decline of several cellular processes. The loss of skeletal muscle mass, termed sarcopenia, is one of the major hallmarks of aging. Aged skeletal muscle exhibits a robust reduction in its regenerative capacity due to dysfunction (i.e., senescence, lack of self‐renewal, and impaired differentiation) of resident muscle stem cells, called satellite cells. To replicate aging in vitro, immortalized skeletal muscle cells (myoblasts) can be treated with various agents to mimic age‐related dysfunction; however, these come with their own set of limitations. In the present study, we used sequential passaging of mouse myoblasts to mimic impaired differentiation that is observed in aged skeletal muscle. Further, we investigated mitochondrial apoptotic mechanisms to better understand the impaired differentiation in these “aged” cells. Our data shows that sequential passaging (>20 passages) of myoblasts is accompanied with significant reductions in differentiation and elevated cell death. Furthermore, high‐passage (HP) myoblasts exhibit greater mitochondrial‐mediated apoptotic signaling through mitochondrial BAX translocation, CYCS and AIFM1 release, and caspase‐9 activation. Finally, we show that inhibition of mitochondrial outer membrane permeability partly recovered differentiation in HP myoblasts. Together, our findings suggests that mitochondrial apoptotic signaling is a contributing factor to the diminished differentiation that is observed in aged myoblasts.