bluuebunny/crossref_metadata_2025_split huggingface dataset:
The causal relationship of DTI phenotypes and epilepsy: A two sample mendelian randomization study
Authors: Feng Shang , Huang Shaobin , Lin Zhiguo 
Published: October 2024

AbstractObjectiveClinical studies indicated a link between DTI imaging characteristics and epilepsy, but the causality of this connection had not been established. Therefore, we employed the Mendelian randomization analysis method to determine the causal relationship between DTI imaging characteristics and epilepsy.MethodWe used Mendelian randomization analysis to identify the causal relationship between brain structure and the risk of epilepsy. GWAS data of DTI phenotypes, focal epilepsy, and genetic generalized epilepsy (GGE) were utilized in the analysis.ResultsOur study found that DTI imaging phenotypes had a causal risk relationship with epilepsy. These phenotypes had a statistical impact on the risk of epilepsy seizures. There were differences in DTI phenotype causality between GGE and focal epilepsy, which were associated with the clinical phenotype differences of the two types of epilepsy.SignificanceOur study demonstrated that the diagnosis of subtypes could be assisted by comparing the differences in DTI phenotypes of specific brain regions. This meant that by studying the changes in brain regions before the onset of epilepsy, we might be able to intervene in epilepsy at an earlier stage.Plain Language SummaryOur study used Mendelian randomization to explore the causal relationship between brain structure, as seen in DTI imaging, and epilepsy. We found that specific DTI phenotypes are linked to an increased risk of epilepsy seizures, with notable differences between genetic generalized epilepsy and focal epilepsy. This suggested that analyzing DTI phenotypes could help in diagnosing and potentially intervening in epilepsy earlier by finding brain changes before seizures begin.
Fatty acid amide hydrolase gene inactivation induces hetero‐cellular potentiation of microglial function in the 5xFAD mouse model of Alzheimer's disease
Authors: Arnanz María Andrea , Ferrer María , Grande María Teresa , de Martín Esteban Samuel Ruiz , Ruiz‐Pérez Gonzalo , Cravatt Benjamin F. , Mostany Ricardo , Lobo Víctor Javier Sánchez‐Arévalo , Romero Julián , Martínez‐Relimpio Ana María 
Published: October 2024

AbstractNeuroinflammation has recently emerged as a crucial factor in Alzheimer's disease (AD) etiopathogenesis. Microglial cells play an important function in the inflammatory response; specifically, the emergence of disease‐associated microglia (DAM) has offered new insights into the conflicting perspectives on the detrimental or beneficial roles of microglia. We previously showed that modulating the endocannabinoid tone by fatty acid amide hydrolase (FAAH) inactivation renders beneficial effects in an amyloidosis context, paradoxically accompanied by an exacerbated neuroinflammatory response and the enrichment of DAM population. Here, we aim to elucidate the role of microglial cells in FAAH‐lacking mice in the 5xFAD mouse model of AD by using RNA‐sequencing analysis, molecular determinations, and morphological studies by using in vivo multiphoton microscopy. FAAH‐lacking AD mice displayed upregulated inflammatory genes and exhibited a DAM genetic profile. Conversely, genes linked to AD were downregulated. Depleting microglia using PLX5622 revealed that plaque‐associated microglia in FAAH‐deficient AD mice had a more stable, ramified morphology and increased Aβ uptake, leading to reduced plaque growth compared to control mice. Importantly, FAAH expression was negligible in microglial cells, thus suggesting a role for FAAH in the cellular interplay in the central nervous system. Our findings show that Faah gene inactivation triggers a hetero‐cellular enhancement of microglial function that was paradoxically paralleled by an exacerbated inflammatory response. Taken together, the present data highlight FAAH as a potential therapeutic target in AD.
PCSK9 Inhibitors: The Evolving Future
Authors: Jeswani Bijay Mukesh , Sharma Shubhangi , Rathore Sawai Singh , Nazir Abubakar , Bhatheja Rohit , Kapoor Kapil 
Published: October 2024

ABSTRACTIntroductionPCSK9 inhibitors are a novel class of medications that lower LDL cholesterol (LDL‐C) by increasing LDL receptor activity, promoting clearance of LDL‐C from the bloodstream. Over the years, PCSK9 inhibitors have been explored as adjunct therapies to statins or as monotherapy in high‐risk cardiovascular patients.AimThis review aims to provide an updated perspective on PCSK9 inhibitors, assessing their clinical efficacy, safety, and significance, especially in light of recent clinical trials.MethodsThe review examines the role of PCSK9 in cholesterol regulation and summarizes the results of major cardiovascular trials, including FOURIER, SPIRE‐1, SPIRE‐2, and ODYSSEY Outcomes. It also discusses emerging treatments like small interfering RNA (siRNA) therapies and evaluates PCSK9 inhibitor effects on LDL‐C and lipoprotein(a) levels.ResultsClinical trials have shown PCSK9 inhibitors reduce LDL‐C by up to 60%. In the FOURIER trial, evolocumab reduced LDL‐C by 59% and major cardiovascular events by 15%–20%. The SPIRE‐2 trial, despite early termination, showed a 21% risk reduction in the primary composite endpoint with bococizumab. The ODYSSEY Outcomes trial reported a 57% LDL‐C reduction with alirocumab, alongside a 15% reduction in adverse events. Emerging treatments like Inclisiran offer long‐term LDL‐C control with fewer doses. PCSK9 inhibitors are generally well‐tolerated, with the most common side effect being injection site reactions.ConclusionPCSK9 inhibitors significantly lower LDL‐C and reduce cardiovascular events, offering promising therapies for high‐risk patients, including those with familial hypercholesterolemia (FH) and those who cannot tolerate statins. Future research will focus on optimizing these inhibitors, integrating complementary therapies, and exploring gene‐editing technologies to improve patient outcomes.
Engineered exosomes in service of tumor immunotherapy: From optimizing tumor‐derived exosomes to delivering CRISPR/Cas9 system
Authors: Jiang Mingyang , Zhang Ke , Meng Jinfeng , Xu Linhua , Liu Ying , Wei Ruqiong 
Published: October 2024

AbstractExosomes can be modified and designed for various therapeutic goals because of their unique physical and chemical characteristics. Researchers have identified tumor‐derived exosomes (TEXs) as significant players in cancer by influencing tumor growth, immune response evasion, angiogeneis, and drug resistance. TEXs promote the production of specific proteins important for cancer progression. Due to their easy accessibility, TEXs are being modified through genetic, drug delivery, membrane, immune system, and chemical alterations to be repurposed as vehicles for delivering drugs to improve cancer treatment outcomes. In the complex in vivo environment, the clustered regularly interspaced short palindromic repeats and CRISPR‐associated protein 9 (CRISPR/Cas9) system encounters challenges from degradation, neutralization, and immune responses, emphasizing the need for strategic distribution strategies for effective genome editing. Engineered exosomes present a promising avenue for delivering CRISPR/Cas9 in vivo. In this review, we will explore different techniques for enhancing TEXs using various engineering strategies. Additionally, we will discuss how these exosomes can be incorporated into advanced genetic engineering systems like CRISPR/Cas9 for possible therapeutic uses.
The Quantitative In Vivo Assessment of Diabetic and Non‐Diabetic Skin Wound Healing Using Phasor‐FLIM Approach
Authors: Zuhayri Hala , Lepekhina Tatiana B. , Nikolaev Viktor V. , Baalbaki Houssain , Knyazkova Anastasia I. , Borisov Alexey V. , Krivova Natalya A. , Kistenev Yury V. 
Published: October 2024

ABSTRACTA quantitative assessment of wound status in a murine model was developed using phasor plot presentation of fluorescence lifetime imaging microscopy (FLIM) data. The quantitative assessment is based on calculating Bhattacharyya distance between g coordinates of FLIM data phasor plot density distributions of wound and healthy skin. The approach was validated for both diabetic and non‐diabetic mice wounds, including during low‐dose photodynamic therapy (LDPDT). Analysis revealed a shift in the FLIM data phasor plot g coordinates, suggesting altered metabolic processes involved in wound healing. Bhattacharyya distances in the LDPDT groups were closer to zero compared to the control group, which was not treated by LDPDT. Bhattacharyya distances in the non‐diabetic LDPDT groups were closer to zero compared to the diabetic LDPDT groups that is consistent with the literature regarding the positive role of LDPDT in accelerating wound healing and the role of diabetes mellitus in impairing wound healing.
An In Vitro Study of 355‐nm Laser Ablation of Atherosclerotic Lesions Model
Authors: Wei Fangying , He Jiajun , Zhao Shiyong , Lei Peng , Zhang Qingjie , Li Guangxi , Li Xiaopeng , Ding Xin , Yao Jianquan 
Published: October 2024

ABSTRACTA study of 355 nm laser with high pulse energy across various types of atherosclerotic lesion models is presented. The 355 nm laser pulses (10 ns) are delivered via a single fiber (600 μm diameter), and the ablation of calcified tissue, lipid tissue, and thrombus‐like tissue are studied under varied laser fluence (40–70 mJ/mm2) and repetition rate (5–30 Hz). The contact and noncontact ablation processes of chicken tibia samples (calcified tissue) are compared at 60 mJ/mm2 and 30 Hz, and the size of ablation particles is in the range of 0.1–1 μm. At the same repetition rate, the advancement rate of tricalcium phosphate samples reaches 150 μm/s at 70 mJ/mm2. Calcified and lipid models demonstrate predictable increases in ablation with higher laser fluence and repetition rate. The fresh porcine blood clot samples exhibit high‐quality ablation with good channel effect at 50 mJ/mm2 and 30 Hz.
Tin Silver Alloy as a Biomaterial: Corrosion Characteristics and Cellular Behavior
Authors: Goodwin Charley M. , Mace Annsley O. , Gilbert Jeremy L. 
Published: October 2024

ABSTRACTTin‐silver (Sn‐Ag) has been used as a permanently implanted biomaterial within the Essure female sterilization device and in dental amalgams; however, little data exist for Sn‐Ag's corrosion characteristics and/or cellular interactions. In this study, to assess its suitability as a degradable metallic biomaterial, 95–5 wt% Sn‐Ag solder was subjected to corrosion testing including open circuit potential (OCP), electrochemical impedance spectroscopy (EIS), and anodic potentiodynamic polarization in phosphate‐buffered saline (PBS) and cell culture media (with serum proteins) at room temperature (25°C) and body temperature (37°C). Cell culture studies were also performed. Mouse pre‐osteoblast cells (MC3T3‐E1) were cultured in media on Sn‐Ag discs and monitored over 24 h at potentials below, around, or above Sn‐Ag's breakdown potential, fixed, and then viewed using SEM. Separately, cells on tissue culture plastic were subjected to increasing concentrations of SnCl2 in media for 24 h before a live‐dead imaging at each concentration to determine cell viability and area fraction covered when compared with a control well. The results show both passive (in PBS), with a breakdown potential of −250 mV versus Ag/AgCl and active polarization behavior (in AMEM with proteins). EIS results showed polarization resistance (R

p
) in the 105 Ωcm2 range but decreased generally with increasing temperature (p < 0.05). Cells were well attached on Sn‐Ag surfaces at OCP and below the breakdown potential, but when anodically polarized, cells reduced their spread area and became more spherical, indicating less viability. SnCl2 exhibited a dose‐dependent killing effect on MC3T3 cells with a lethal dose for 50% of about 0.5 mM. The results of these experiments show that Sn‐Ag alloys can be considered as degradable metallic biomaterials.
Stable, aromatic, and electrophilic azepinium ions: Design using quantum chemical methods
Authors: Patra Nabajyoti , Gupta Astha , Bharatam Prasad V. 
Published: October 2024

AbstractCyclic nitrenium ions containing five‐membered and six‐membered rings are available, however, the seven‐membered cyclic nitrenium ions (azepinium ions) are rare. The chemistry of these species is related to their stability originating from the aromaticity due to 6π electrons. Very few theoretical and experimental studies have been conducted on the azepinium ions. Related clozapine and olanzapine cations (diazepinium ions) were observed during drug metabolism studies. In this work, quantum chemical analysis has been carried out to estimate the stability, aromaticity, and electrophilicity of several derivatives of azepinium ions. A few of the designed azepinium ions carry ΔES‐T values in the range of 50 kcal/mol favoring singlet state; π donating groups at the 2nd position increase the singlet‐triplet energy differences. Most of the substituents reduce the NICS(1) values compared to the parent system. Ring fusion with heterocyclic five‐membered rings generally increases the aromaticity and the stability of the azepinium ion ring systems. The electrophilicity parameters estimated in terms of HIA, FIA, and ω values indicate that it is possible to fine‐tune the chemical properties of azepinium ions with appropriate modulation.
Electrochemical Applications Reveal Enhanced Photocatalytic Performance of TiO2‐Doped ZnS Nanocomposites
Authors: Synthiya S. , Thilagavathi T. , Uthrakumar R. , Renuka R. , Inmozhi C. , Kaviyarasu K. 
Published: October 2024

ABSTRACTThe titanium dioxide (TiO2) nanoparticles were prepared by hydrothermal methods at ambient temperature. Based on XRD analysis, the average crystallite size of pure TiO2 nanoparticles and those doped with ZnS was calculated to be 58 and 54 nm, respectively. At an angle of 25.4°, the prominent peak observed at the (101) plane of TiO2 was confirmed. As can be seen from the collection of peaks, the TiO2 formed has an anatase‐type tetragonal crystal structure. A strain of −6.4541 × 10−4 and a grain size of 33 nm can be seen in the W–H plot for TiO2 nanoparticles. For doped ZnS nanoparticles, on the other hand, the values are 1.9448 × 10−4 and 47 nm. In our study, we found that doped nanoparticles were average grain size 134 nm, while pure nanoparticles were average grain size 146 nm. Doping reduces the size of the nanomaterial, which means that the TiO2 molecules form nanoclusters on their surfaces, which can lead to a larger grain size for a pure nanoparticle than for a doped nanoparticle. A wide range of functional groups and their associated bonds were investigated using FTIR spectra in synthesized nanomaterials. TiOTi bonds are subjected to a strong stretching vibration, which is confirmed by the absorption peaks from 450 cm−1 to 800 cm−1. The PL spectra for pure TiO2‐ and ZnS‐doped TiO2 containing nanocomposites of ZnS emit ultraviolet light at wavelengths of 362 and 379 nm in the UV region. Pure and doped samples with optical bandgap energies of ~3.04 and ~3.8 eV corresponding to anatase phases were near ~3.18 eV in Tauc plots. Since the TiO2‐doped ZnS heterojunction migrates photoexcited holes toward the interface, while electrons migrate toward the bulk, this results in photoexcited holes migrating toward the interface. To calculate the specific capacitance of the synthesized materials, cyclic voltammetry with pure ZnS and those with ZnS‐doped had specific capacitance values of 144.91 F/g and 120.11 F/g, respectively. The catalysts used were ZnS nanocomposite doped with TiO2 in addition to pure TiO2 nanoparticles. The degradation of dye within 80 min after sunlight exposure was monitored with a UV–Vis spectrophotometer at 20‐min intervals. ZnS nanoparticles doped with TiO2 display 87.8% greater efficiency than pure nanoparticles. Doped TiO2 nanocomposite degrades at an 87.8% rate, whereas pure TiO2 degrades at ~54%, indicating that the dopants enhance photocatalysis.
Mechanisms of extracellular vesicle uptake and implications for the design of cancer therapeutics
Authors: Jackson Cullison Stephanie R. , Flemming Joseph P. , Karagoz Kubra , Wermuth Peter J. , Mahoney Mỹ G. 
Published: October 2024

AbstractThe translation of pre‐clinical anti‐cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose‐limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off‐target toxicity. Much effort has been devoted to the rational design and application of synthetic nanoparticles to serve as targeted therapeutic delivery vehicles. Several challenges to the successful application of this modality as delivery vehicles include the induction of a protracted immune response that results in their rapid systemic clearance, manufacturing cost, lack of stability, and their biocompatibility. Extracellular vesicles (EVs) are a heterogeneous class of endogenous biologically produced lipid bilayer nanoparticles that mediate intercellular communication by carrying bioactive macromolecules capable of modifying cellular phenotypes to local and distant cells. By genetic, chemical, or metabolic methods, extracellular vesicles (EVs) can be engineered to display targeting moieties on their surface while transporting specific cargo to modulate pathological processes following uptake by target cell populations. This review will survey the types of EVs, their composition and cargoes, strategies employed to increase their targeting, uptake, and cargo release, and their potential as targeted anti‐cancer therapeutic delivery vehicles.
Short‐ and long‐term outcomes of liver resection with hepatic vein reconstruction for liver tumors: A nationwide multicenter survey
Authors: Sadamori Hiroshi , Hasegawa Kiyoshi , Oba Atsushi , Kato Yutaro , Soejima Yuji , Monden Kazuteru , Umeda Yuzo , Abe Yuta , Ko Saiho , Saiura Akio , Ohtsuka Masayuki , Kubo Shoji , Shirabe Ken , Nagano Hiroaki , Fujiwara Toshiyoshi , Nakamura Masafumi , Endo Itaru 
Published: October 2024

AbstractBackground/PurposeThis study clarifies the short‐ and long‐term outcomes of liver resection with hepatic vein (HV) reconstruction for liver tumors and identifies the risk factors for poor outcome.MethodsWe contacted 263 specialized centers in Japan and collected data on this surgical procedure. Patient characteristics, surgical procedures, and outcomes were then analyzed.ResultsA total of 187 patients were enrolled from 36 institutions. Grade C post‐hepatectomy liver failure (PHLF) and in‐hospital mortality were 3.2% and 1.6%, respectively. The median overall survival (OS) and recurrence‐free survival (RFS) were 49.9 and 9.8 months, respectively. Surgical outcomes, OS and RFS did not differ among three types of liver tumors, colorectal liver metastasis (CRLM) (n = 127), hepatocellular carcinoma (n = 27), and intrahepatic cholangiocarcinoma (n = 27). Patients with CRLM and seven or more courses of preoperative chemotherapy had significantly worse OS. Compared with HV reconstruction for securing liver remnant (LR) function (n = 148), reconstruction of the only main HV remaining in the LR (n = 39) had significantly worse short‐term outcomes, but did not result in increased mortality, and showed equivalent OS and RFS.ConclusionsLiver resection with HV reconstruction can be achieved safely and contributes to a relatively good long‐term outcome for patients with advanced liver malignancies.
Reducing the Uncertainty in the Tropical Precipitation through a Multi‐Criteria Decision‐Making Approach
Authors: Majhi Archana , Dhanya C. T. , Pattanayak Sonali , Chakma Sumedha 
Published: October 2024

ABSTRACTThe inherent model uncertainty in precipitation projections is found to be more dominant over tropical regions thereby reducing the reliability of using them in climate change impact assessment studies. To address such issues, a subset of well performing global climate models (GCMs) can provide narrow range of possible future outcomes, which can be helpful in formulating mitigation and adaptation strategies that are more targeted and efficient. In this study, climate models are selected based on their performance in simulating relative humidity and vertical velocity since these variables play an important role in precipitation simulation and significantly contribute toward the intermodel spread. The models are evaluated by using various statistical performance measures and ranked using multi‐criteria decision‐making approaches. Finally, based on Jenks natural breaks optimization algorithm, subset of GCMs consisting of ACCESS1.0, ACCESS1.3 and INM‐CM4 models, are considered as the best possible subset for precipitation simulation over tropical land regions. Two observational precipitation datasets are further considered to investigate the effectiveness of the proposed framework. The proposed methodology is validated to be effective in identifying the best climate models since the resulting subset is capable of both capturing observed precipitation and minimizing the uncertainty in future projections. Hence, this methodology can be utilized further for performance evaluation of GCMs focusing different geography and climatic drivers.
Advanced Intelligent Anti‐Counterfeiting in a Memory Storage Phosphor Through Response of Charge Carriers to Temperature
Authors: Zhang Xiangyu , Wang Zhigang , Xu Chunlong , Gao Dangli , Pang Qing , Xu Jie , Wang Xiaojun 
Published: October 2024

AbstractPersistent phosphor as a printing anti‐counterfeiting material has attracted strong attention owing to its inherent luminescent decay process and multi‐mode luminescence characteristics under external field stimulation. However, the dynamic persistent luminescence (PersL) pattern of a single material is only manifested in color changes and still faces the problem of being easily decrypted. Herein, a multi‐color luminescent material with a wide range distribution of traps is developed, which can emit strong white PersL. In addition, the phosphors show an intelligent response of thermo‐stimulated luminescence to ambient temperature via recalling the charging temperature of the traps. The PersL mechanism is proposed based on electron transfer between PbO6 and TbO6 octahedrons through the O bridging. Based on the intelligent response of thermo‐stimulated luminescence to temperature, high‐throughput multi‐channel luminescence anti‐counterfeiting can be achieved on a single phosphor recording layer. This study not only provides further insights into the PersL mechanism, but also opens a new door for constructing intelligent responsive anti‐counterfeiting materials.