bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrocatalytic Reduction of CO2 to Long‐Chain Hydrocarbons: Investigating the Asymmetric C−C Coupling Mechanism on Pd3Au Catalysts
Authors: Zheng Ming , Lv Chade , Zhou Xin
Published: January 2025

The electrochemical reduction of CO2 to high‐energy‐density hydrocarbons is pivotal for addressing energy and environmental challenges. Understanding the mechanisms underlying the conversion of CO2 to long‐chain hydrocarbons is both crucial and complex. In this study, we employed density functional theory (DFT) calculations to investigate the C−C coupling mechanisms responsible for the formation of C2‐C4 products on Pd3Au catalysts. Our findings highlight the sequential formation of C2−C1 bonds via asymmetric C−C coupling as a critical pathway for generating C3 product, which is essential for controlling product selectivity. Detailed analysis of coupling reactions involving CCH2* and CCH3* intermediates with various C1 species indicates that these asymmetric coupling events are energetically favorable and play a decisive role in the selective assembly of carbon atoms into longer hydrocarbon chains. Moreover, we propose a mechanism wherein the asymmetric coupling of C1‐C3 intermediate leads to a diverse array of C4 products. This process underscores the importance of CH2 group coupling with C3 intermediates in forming long‐chain hydrocarbons. Our work provides valuable insights into optimizing catalyst design for improved selectivity towards higher hydrocarbons in CO2 reduction processes.
Efficient Blue Electroluminescence Based on a Donor‐π‐Acceptor with Pyrene Bridge: Weak Charge‐Transfer (CT) for High Luminescence and Considerable Exciton Utilization
Authors: Yao Mingming , Men Shuyi , Yu Kuo , Wei Jinbei , Zhang Shi‐Tong , Yang Bing
Published: January 2025

Blue emitters are crucial in the organic light emitting diode (OLED) industry and scientific field. In this work, we prepared a novel donor‐π‐acceptor (D‐π‐A) molecular PCZ−P‐PY using pyrene as a bridge to construct hybrid local and charge‐transfer (HLCT) state with weak charge‐transfer (CT) property. This excited state design give rise to the high photoluminescent quantum yield (PLQY), more importantly, it is also responsible for the high exciton utilization efficiency (EUE) by constructing efficient hot‐exciton channel. As a result, exceeding external quantum efficiency (EQE) of 5.7 % is achieved in the non‐doped OLED of PCZ−P‐PY with exceeding EUE of up to 90 %.
Nitrocyclopropanes as Valuable Building Blocks in Organic Synthesis and Biology: Exploring the Origin of the Nitro Group
Authors: Chaidali Andriani G. , Terzidis Michael A. , Lykakis Ioannis N.
Published: January 2025

Cyclopropane derivatives serve as important building blocks in organic synthesis, due to their three‐membered stretched ring. Nitro‐substituted cyclopropanes (NCPs) represent a special class of donor‐acceptor cyclopropanes (DACs) that contain a strong electron‐withdrawing nitro group as substituent on the cyclopropyl moiety. Due to the versatile nature of the nitro group, which can be converted into other functional azo groups or heterocyclic scaffolds, NCPs are considered important building blocks in the design of complex organic compounds. Herein, the present review is organized in two main sections focused on the synthesis and application of NCPs. The part containing the synthetic methodologies of NCPs has been further divided into distinct sections based mainly on the nature of the starting materials, such as: a) from nitroalkenes, b) from nitro‐bearing diazo compounds, c) from nitroalkanes in combination with alkenes, d) from aminocyclopropanes under oxidative conditions, and e) from various nitro compounds, through miscellaneous processes. In the part concerning the applications and use of NCPs, the categorization includes three main subcategories, concerning their reduction to 1‐aminocyclopropane‐1‐carboxylic acids (ACC), the ring opening of NCPs leading to valuable open‐chain heterocycles, and the ring expansion to larger cyclic and heterocyclic compounds.
Helicene–Fluorescein Hybrids: A Reversible Base‐Triggered (Chir)optical Switch with Sign Inversion of Circularly Polarized Luminescence
Authors: Miwa Sorachi , Mizutani Daichi , Kawano Kenichi , Matsuzaki Katsumi , Nagata Yuuya , Tsubaki Kazunori , Takasu Kiyosei , Takikawa Hiroshi
Published: January 2025

Novel circularly‐polarized‐luminescence (CPL) materials were designed and synthesized by integrating the intrinsic chirality of helicene with the acid/base‐responsive properties of fluorescein. The synthesized helicene–fluorescein hybrids exhibit reversible switching between blue fluorescence under neutral conditions and red fluorescence under basic conditions. Furthermore, these hybrid compounds demonstrate unique chiroptical switching behavior with a rare base‐triggered CPL sign inversion, where (P)‐isomers show a negative CPL signal around 450 nm under neutral conditions and a positive signal around 620 nm under basic conditions, with three‐fold enhanced dissymmetry factors (|glum|) under basic conditions. The structural basis for this switching was elucidated through TD‐DFT calculations, revealing distinct angles between magnetic and electric transition dipole moments in closed versus open forms. Live‐cell imaging experiments using HeLa cells revealed that the hybrid compounds exhibit intracellular red emission with minimal cytotoxicity, thus promising potential as chiral fluorescent probes for biological applications.
Lamellarin D Acts as an Inhibitor of Type I Collagen Production
Authors: Okuno Daisuke , Sakamoto Noriho , Hayashi Hideki , Fukuda Tsutomu , Akiyama Yoshiko , Iketani Chiaki , Murakami Ritsuko , Tokito Takatomo , Miyamura Takuto , Yura Hirokazu , Kido Takashi , Ishimoto Hiroshi , Takemoto Shinnosuke , Takazono Takahiro , Nishino Tomoya , Ishimatsu Yuji , Ishihara Jun , Takeda Kohsuke , Tanaka Yoshimasa , Mukae Hiroshi
Published: January 2025

Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic interstitial lung disease characterized by irreversible loss of lung function and a poor prognosis. Type I collagen, a major component of the extracellular matrix, plays a central role in the pathogenesis of fibrosis and is considered a key molecular target for therapeutic intervention. While current anti‐fibrotic therapies demonstrate limited efficacy in slowing disease progression, their clinical impact remains suboptimal due to poor pharmacokinetic properties and non‐curative therapy. Moreover, the development of effective anti‐fibrotic agents targeting collagen synthesis is hindered by the absence of robust, cost‐effective, high‐throughput drug screening platforms. In this study, we established a novel screening system designed to identify small molecules that inhibit the expression of the COL1A2 gene, which encodes type I collagen. Utilizing this system, we screened a library of natural and synthetic compounds developed at Nagasaki University and identified lamellarin D as a potent inhibitor of COL1A2 expression and subsequent type I collagen production. These findings suggest that lamellarin D, through its unique molecular mechanism, may serve as the foundation for the development of a new class of IPF treatments aimed at targeting the underlying fibrotic processes.
Integrating UAV‐based multispectral remote sensing and machine learning for detection and classification of chocolate spot disease in faba bean
Authors: Mohammadi Shirin , Uhlen Anne Kjersti , Aamot Heidi Udnes , Dieseth Jon Arne , Shafiee Sahameh
Published: January 2025

Chocolate spot (CS), caused by Botrytis fabae, is one of the most destructive fungal diseases affecting faba bean (Vicia faba L.) globally. This study evaluated 33 faba bean cultivars across two locations and over 2 years to assess genetic resistance and the effect of fungicide application on CS progression. The utility of unmanned aerial vehicle–mounted multispectral camera for disease monitoring was examined. Significant variability was observed in cultivar susceptibility, with Bolivia exhibiting the highest level of resistance and Louhi, Sampo, Vire, Merlin, Mistral, and GL Sunrise proving highly susceptible. Fungicide application significantly reduced CS severity and improved yield. Analysis of canopy spectral signatures revealed the near‐infrared and red edge bands, along with enhanced vegetation index (EVI) and soil adjusted vegetation index, as most sensitive to CS infection, and they had a strong negative correlation with CS severity ranging from −0.51 to −0.71. In addition, EVI enabled early disease detection in the field. Support vector machine accurately classified CS severity into four classes (resistant, moderately resistant, moderately susceptible, and susceptible) based on spectral data with higher accuracy after the onset of disease compared to later in the season (accuracy 0.75–0.90). This research underscores the value of integrating resistant germplasm, sound agronomic practices, and spectral monitoring for effectively identification and managing CS disease in faba bean.
Impact of sleep disruptions on gray matter structural covariance networks across the Alzheimer's disease continuum
Authors: Luo Xiao , Li Kaicheng , Zeng Qingze , Liu Xiaocao , Li Jixuan , Zhang Xinyi , Zhong Siyan , Liu Lingyun , Wang Shuyue , Wang Chao , Chen Yanxing , Zhang Minming , Huang Peiyu ,   for the Alzheimer's Disease Neuroimaging Initiative (ADNI)
Published: January 2025

BACKGROUND

This study explores the impact of sleep disturbances on gray matter structural covariance networks (SCNs) across the Alzheimer's disease (AD) continuum.

METHODS

Amyloid‐negative participants served as controls, whereas amyloid positive (A+) individuals were categorized into six groups based on cognitive status and sleep quality. SCNs for the default mode network (DMN), salience network (SN), and executive control network (ECN) were derived from T1‐weighted magnetic resonance images.

RESULTS

In the DMN, increased structural associations were observed in cognitive unimpaired (CU) A+ and mild cognitive impairment (MCI) groups regardless of sleep quality, whereas AD with poor sleep (PS) showed a decrease and AD with normal sleep (NS) an increase. For the ECN, AD‐NS showed increased and AD‐PS showed reduced associations. In the SN, reduced associations were observed in CU A+ NS and MCI‐NS, whereas AD‐NS displayed increased associations; only AD‐PS had decreased associations.

CONCLUSION

Distinct SCN damage patterns between normal and poor sleepers provide insights into sleep disturbances in AD.

Highlights

We delineated distinct patterns of structural covariance networks (SCN) impairment across the Alzheimer's disease (AD) continuum, uncovering significant disparities between individuals with normal sleep architecture and those afflicted by sleep disturbances.

These observations underscore the pivotal importance of addressing sleep disruptions in AD therapeutics, providing a refined understanding of their detrimental impact on brain networks implicated in the disease.

Our investigation epitomizes methodological precision by constructing an AD continuum using amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers to minimize diagnostic heterogeneity, further enhanced by a substantial cohort size that bolsters the robustness and generalizability of our findings.
TR(Acking) Individuals Down: Exploring the Effect of Temporal Resolution in Resting‐State Functional MRI Fingerprinting
Authors: Cassone Barbara , Saviola Francesca , Tambalo Stefano , Amico Enrico , Hübner Sebastian , Sarubbo Silvio , Van De Ville Dimitri , Jovicich Jorge
Published: January 2025

Functional brain fingerprinting has emerged as an influential tool to quantify reliability in neuroimaging studies and to identify cognitive biomarkers in both healthy and clinical populations. Recent studies have revealed that brain fingerprints reside in the timescale‐specific functional connectivity of particular brain regions. However, the impact of the acquisition's temporal resolution on fingerprinting remains unclear. In this study, we examine for the first time the reliability of functional fingerprinting derived from resting‐state functional MRI (rs‐fMRI) with different whole‐brain temporal resolutions (TR = 0.5, 0.7, 1, 2, and 3 s) in a cohort of 20 healthy volunteers. Our findings indicate that subject identifiability within a fixed TR is successful across different temporal resolutions, with the highest identifiability observed at TR 0.5 and 3 s (TR(s)/identifiability(%): 0.5/64; 0.7/47; 1/44; 2/44; 3/56). We discuss this observation in terms of protocol‐specific effects of physiological noise aliasing. We further show that, irrespective of TR, associative brain areas make an higher contribution to subject identifiability (functional connections with highest mean ICC: within subcortical network [SUB; ICC = 0.0387], within default mode network [DMN; ICC = 0.0058]; between DMN and somato‐motor [SM] network [ICC = 0.0013]; between ventral attention network [VA] and DMN [ICC = 0.0008]; between VA and SM [ICC = 0.0007]), whereas sensory‐motor regions become more influential when integrating data from different TRs (functional connections with highest mean ICC: within fronto‐parietal network [ICC = 0.382], within dorsal attention network [DA; ICC = 0.373]; within SUB [ICC = 0.367]; between visual network [VIS] and DA [ICC = 0.362]; within VIS [ICC = 0.358]). We conclude that functional connectivity fingerprinting derived from rs‐fMRI holds significant potential for multicentric studies also employing protocols with different temporal resolutions. However, it remains crucial to consider fMRI signal's sampling rate differences in subject identifiability between data samples, in order to improve reliability and generalizability of both whole‐brain and specific functional networks' results. These findings contribute to a better understanding of the practical application of functional connectivity fingerprinting, and its implications for future neuroimaging research.
Stage‐specific characterization of “early‐onset colorectal cancer”: Localized and synchronous metastatic disease
Authors: Akkus Erman , Karaoğlan Beliz Bahar , Kayaalp Mehmet , Turmuş Utkucan , Akyol Cihangir , Utkan Güngör
Published: January 2025

Early‐onset colorectal cancer (EOCRC) is an alarming entity worldwide. Yet, stage‐specific characteristics and prognosis in localized and synchronous metastatic EOCRC are not well‐defined. Two cohorts of CRC patients (localized and synchronous metastatic) were evaluated, defining EOCRC as the diagnosis <50 years old. Five hundred sixty‐eight patients were included (n = 432 localized, 14.4% [n = 62] EOCRC and n = 136 synchronous metastatic, 20.6% [n = 28] EOCRC). 93.5% of localized and 96.5% of synchronous metastatic EOCRC patients were symptomatic at diagnosis. Among localized patients, female gender (58.1% vs. 40%, p = .008), perineural invasion (41.9% vs. 24.9%, p = .005), folinic acid, 5‐fluorouracil, and oxaliplatin chemotherapy (45.2% vs. 25.2%, p = .003), and perioperative chemotherapy cycles (9.21 [± 3.10] vs. 7.98 [± 2.92], p = .006) were higher in EOCRC compared with ≥50‐year. Median recurrence‐free survival (RFS) and overall survival were not reached in either group (p = .234 and p = .831). Only RAS mutant status was associated with RFS (Hazard ratio: 7.09 [95% confidence interval (CI): 1.87–26.76], p < .001) in EOCRC. Among synchronous metastatic patients, urgent surgery (32.1% vs. 11.1%, p = .014) and local treatments (39.3% vs. 20.4%, p = .037) were more frequent in EOCRC. Median progression‐free survival and overall survival in the EOCRC and ≥50 years were 8.07 months (95% CI: 5.03–12.97) vs. 10.03 months (95% CI, 8.40–13.10) (p = .450) and 18.57 months (95% CI, 13.33–43.03) vs. 19.83 months (95% CI, 16.07–27.30) (p = .833), respectively. Synchronous metastatic EOCRC more frequently underwent urgent surgery (32.1% vs. 8%, p = .008) and had RAS mutation (43.5% vs. 16.7%, p = .032) than localized EOCRC. This study suggests that localized and synchronous metastatic EOCRC patients may have different characteristics than average onset, without survival differences. Implementation of stage‐specific characteristics into daily practice is necessary for decision‐making processes in these young patients.
Evaluation of plasma alpha‐1‐antichymotrypsin as a marker for pulmonary Kaposi sarcoma
Authors: Nalwoga Angela , Jackson Conner , Fiorillo Suzanne , Manyeruke Felix , Makoni Tobias , Nyagura Tatenda , White Irene E. , Rapaport Eric , Rochford Rosemary , Borok Margaret , Campbell Thomas B.
Published: January 2025

Individuals with AIDS and Kaposi sarcoma (AIDS‐KS) with pulmonary involvement have high‐risk of poor outcomes but diagnosis of pulmonary KS in low‐resource settings is difficult. We aimed to discover plasma proteins that distinguish individuals with pulmonary KS from those without pulmonary involvement. SomaScan proteomics screen measured 7288 plasma proteins in 22 cases and 17 controls selected from 181 participants with HIV‐1 and cutaneous KS who underwent bronchoscopy. Cases had KS in the lower respiratory tract by bronchoscopy. Controls had no KS lesions detected by bronchoscopy. Results of the proteomics screen were confirmed by ELISA measurement of plasma alpha‐1‐antichymotrypsin (SERPINA3) in 18 cases and 13 controls and in an additional 162 individuals with AIDS‐KS who were not included in the case–control analysis. Proteomics identified 12 plasma proteins with differential levels in controls and cases. Plasma alpha‐1‐antichymotrypsin (SERPINA3) complex was consistently higher in cases compared to controls in the proteomics assay. Measurement of plasma alpha‐1‐antichymotrypsin by ELISA confirmed higher levels in cases (median 399.4, IQR 95.77–766.4 μg/ml) versus controls (median 39.98, IQR 31.2–170.2 μg/ml; p = .001). Plasma alpha‐1‐antichymotrypsin correlated with the estimated burden of pulmonary KS in the respiratory tract (r = 0.439; p = .0002) and 234 μg/ml had 51% sensitivity and 94% specificity for detection of pulmonary KS by bronchoscopy. Measurement of plasma alpha‐1‐antichymotrypsin has potential for identifying persons with pulmonary AIDS‐KS and estimating the burden of KS in the lower respiratory tract.
Effects of the expansion of integrated maternal‐fetal intensive care centers on high‐risk newborns in Korea
Authors: Jang Ye Seul , Jang Sung‐In , Park Eun‐Cheol
Published: January 2025

Objective

To investigate the impact of the introduction of Integrated Maternal‐Fetal Intensive Care Unit (MFICU) reimbursement rates for high‐risk newborns in South Korea.

Method

The present study used data from the Population Dynamics data released annually by Statistics Korea, which contain information on all births in the country from October 1, 2015, to September 31, 2019. The MFICU reimbursement fee began on October 1, 2017, and the follow‐up period was 24 months before and after the intervention. The dependent variable was defined as either premature births (before 37 weeks of pregnancy) or underweight births (birth weight ≤2.5 kg). A total of 1 377 841 infants were included in the present study, and an Interrupted Time Series with segmented regression analysis was performed.

Results

After the intervention, the premature or low‐birth‐weight deliveries decreased by approximately 0.4%. The difference in the level change was more significant in legitimate children and multiple births. Premature neonates showed a significantly different level of change compared with low‐birth‐weight neonates.

Conclusion

The expansion of the MFICU reduces high‐risk births, such as premature births and those involving low birth weight. To effectively care for high‐risk deliveries, the enhancement of obstetric care and continuous medical support policies must be maintained.
Celecoxib Enhances Oxidative Muscle Fibre Formation and Improves Muscle Functions Through Prokr1 Activation in Mice
Authors: Park Jeong Hwan , Mok Jongsoo , Park Seoah , Kim Dooho , Kang Min‐Su , Park Tae Sub , Park Joonghoon
Published: January 2025

Background

Muscle diseases are serious challenges to human health. Prokineticin receptor 1 (PROKR1) has emerged as a potential target to improve muscle function through increasing oxidative muscle fibres, but there are no clinically applicable synthetic PROKR1 agonists.

Methods

Drugs with biological properties of prokineticin 2 (PK2) were discovered through connectivity map (CMap) analysis. Their effects on PROKR1 were evaluated using molecular docking, PROKR1 signalling and competitive binding assays. Pregnant dams were fed diets containing varying celecoxib concentrations (0, 500, 1000 and 1500 ppm) from gestation day 5 through weaning. Offspring were given high‐fat diets (HFD) from weaning until 20 weeks old, and body composition, insulin resistance, energy expenditure, exercise performance and histological analysis of muscle tissues were evaluated.

Results

Celecoxib, with a connectivity score of 64.19 to PK2 and a docking score of −9.0 to PROKR1, selectively activated Gs signalling at 4 μM of EC50 and increased NR4A2 protein levels by 1.6‐fold (p < 0.01) in PROKR1‐overexpressing cells. It competitively inhibited PK2 binding to PROKR1 and reduced cAMP accumulation. In murine and human myotubes, celecoxib increased Prokr1 protein levels by 1.8‐fold (p < 0.05), pCreb by 1.5‐fold (p < 0.05) and Nr4a2 by 1.3‐fold (p < 0.05). It also elevated Myh7 index by 2.2‐fold (p < 0.0001), mitochondrial content by 1.6‐fold (p < 0.001) and fatty acid oxidation (FAO) activity by 4.1‐fold (p < 0.05). Offspring exposed to celecoxib during pre‐ and postnatal muscle development exhibited activated Prokr1 signalling, enhanced oxidative muscle fibre formation and improved muscle phenotype despite HFD. At weaning, both male and female offspring showed dose‐dependent increases in lean mass (> 9.35%, p < 0.001) and grip strength (< 18.0%, p < 0.01). At 12 weeks old, mice displayed a dose‐dependent decrease in weight loss (> 13.3%, p < 0.05), increased lean mass (> 16.2%, p < 0.05), improved insulin resistance (> 70.4%, p < 0.0001), energy expenditure (> 173%, p < 0.0001) and grip strength (> 23.5%, p < 0.001). Celecoxib also increased Myh7‐positive muscle fibre composition (> 10.8%, p < 0.05) and mitochondrial mass (> 32.8%, p < 0.05) in the gastrocnemius and soleus muscles, accompanied by significant Prokr1 signalling activation. These effects persisted in both male and female mice at 20 weeks old.

Conclusions

Celecoxib shows promise as a PROKR1 agonist and clinically applicable exercise mimetic for the treatment of muscular disorders.
Defective Cystic Fibrosis Transmembrane Conductance Regulator Accelerates Skeletal Muscle Aging by Impairing Autophagy/Myogenesis
Authors: Chen Ziyi , Xu Jiankun , Hu Peijie , Du Wanting , Chen Junjiang , Zhang Xiaotian , Zhou Wei , Gao Jiayang , Zhang Yuantao , Dai Bingyang , Nie Guangshuai , Hu Jun , Zhou Liangbin , Xu Shunxiang , Chan Hisao Chang , Cheung Wing‐hoi , Ruan Ye Chun , Qin Ling
Published: January 2025

Background

Regenerative capacity of skeletal muscles decreases with age. Deficiency in cystic fibrosis transmembrane conductance regulator (CFTR) is associated with skeletal muscle weakness as well as epithelial cell senescence. However, whether and how CFTR plays a role in skeletal muscle regeneration and aging were unclear.

Methods

Vastus lateralis biopsy samples from male and female human subjects (n = 23) of 7‐ to 86‐year‐old and gastrocnemii tissues from mice of 4‐ to 29‐month‐old were examined for CFTR expression. Skeletal muscle tissues or cultured myoblasts from mice carrying CFTR mutation (DF508) at 4‐ to 18‐month‐old were used for assessment of muscle mass, contractile force and regenerative capacity as well as myogenic and autophagy signalling. Overexpression of LC3‐β, an autophagy mediator, was conducted to reverse myogenic defects in DF508 myoblasts. Adenoviruses containing CFTR gene or pharmaceuticals that enhance CFTR (VX809) were locally injected into the gastrocnemius or femoris quadricep to rescue age‐related skeletal muscle defects in mice.

Results

mRNA levels of CFTR in human vastus lateralis exhibited significantly negative correlations with age (r = −0.87 in males and −0.62 in females, p < 0.05). Gastrocnemius mRNA level of CFTR decreased by 77.7 ± 4.6% in 29‐month‐old wild‐type mice compared to the 4‐month‐old. At 18‐month‐old, DF508 mice showed significantly reduced lean mass (by 35.6%), lower specific twitch force of the gastrocnemius (by 46.2%), decrease in fast/slow‐twitch muscle isoform ratio as well as downregulation of myogenic (e.g., MYOD and MYOG) or autophagy/mitophagy (e.g., LC3‐β) genes, compared to age‐matched wild‐types. Post‐injury gastrocnemius regeneration was found impaired in DF508 mice. Myoblast cultures from DF508 mice showed defective myogenic differentiation, which was reversed by overexpressing LC3‐β. In aged (> 15‐month‐old) mice, overexpressing CFTR or VX809 restored the expression of autophagy or myogenic genes, increased mitochondrial LC3‐β level and improved skeletal muscle mass and function.

Conclusion

Age‐related reduction in skeletal muscle expression of CFTR impairs autophagy and myogenesis, exacerbating skeletal muscle aging. Enhancing CFTR might be a potential treatment strategy for age‐related skeletal muscle disorders.
Inhalable Nano Formulation of Cabazitaxel: A Comparative Study with Intravenous Route
Authors: Kaga Elif , Kaga Sadik , Altunbas Korhan , Okumus Nurullah
Published: January 2025

Chemotherapy is generally given by intravenous (IV) administration which provides higher bioavailability than other systemic routes. However, in the case of lung cancer, the pulmonary (INH) route is the other choice for inhalable formulations. In the study, biochemical and histological parameters of Cabazitaxel (CBZ) free (2 mg kg−1) and nanoparticle (NP) (2 mg kg−1 CBZ equivalent) formulations are investigated after IV and INH administration in rats. The nanoformulation of CBZ is obtained using PEGylated polystyrene (PEG‐PST) nanoparticles obtained by PISA. While a nose and head‐only device is used for INH administration, a jugular vein is used as the IV route. Blood samples (blank, 24 h, and 48 h) are collected via carotid artery cannulas without handling in metabolism cages. According to biochemical parameters, free CBZ formulation applied via IV or INH route shows higher systemic toxicity. On the other hand, the nanoformulation of CBZ showed no signs of toxicity in both IV or INH routes. Higher and longer retention is observed in the case of inhaled nanoformulation. Histological analysis showed higher alveolar macrophage migration for inhaled nanoformulation due to enhanced retention. Results showed that nanotechnology and the lung defense system gave the advantage to end up with an inhalable nanomedicine formulation for lung cancer.
Predicting the Price of Molecules Using Their Predicted Synthetic Pathways**
Authors: Abderrahmane Massina , Tajmouati Hamza , Ribeiro da Silva Vinicius Barros , Perron Quentin
Published: January 2025

Currently, numerous metrics allow chemists and computational chemists to refine and filter libraries of virtual molecules in order to prioritize their synthesis. Some of the most commonly used metrics and models are QSAR models, docking scores, diverse druggability metrics, and synthetic feasibility scores to name only a few. To our knowledge, among the known metrics, a function which estimates the price of a novel virtual molecule and which takes into account the availability and price of starting materials has not been considered before in literature. Being able to make such a prediction could improve and accelerate the decision‐making process related to the cost‐of‐goods. Taking advantage of recent advances in the field of Computer Aided Synthetic Planning (CASP), we decided to investigate if the predicted retrosynthetic pathways of a given molecule and the prices of its associated starting materials could be good features to predict the price of that compound. In this work, we present a deep learning model, RetroPriceNet, that predicts the price of molecules using their predicted synthetic pathways. On a holdout test set, the model achieves better performance than the state‐of‐the‐art model. The developed approach takes into account the synthetic feasibility of molecules and the availability and prices of the starting materials.
Orbicularis Oculi Stimulated Jitter Analysis in Children With Autoimmune Myasthenia Gravis
Authors: Natarajan Vishva , Verma Sumit
Published: January 2025

Introduction/Aims

Stimulated jitter analysis (stim‐JA) involves analyzing the variation in time intervals between stimulations and action potentials, expressed as the mean consecutive difference (MCD). The MCD upper limits are derived from adult populations and warrant a re‐evaluation in children to accurately diagnose neuromuscular junction (NMJ) defects.

Methods

A retrospective chart review was conducted which analyzed orbicularis oculi stim‐JA studies performed on children between January 2014 and December 2021. The clinical profile, acetylcholine receptor (AChR), and muscle‐specific kinase (MuSK) antibody status as well as stim‐JA study results were retrieved. Bootstrapping was applied to the stim‐JA studies to derive de novo MCD upper limits.

Results

Twenty‐seven stim‐JA studies were performed on patients aged 3–19 years with either definite myasthenia gravis presentations and NMJ defects (n = 19, 17 AChR+, 2 MuSK+) or those with normal neurological examinations who were seronegative (n = 8). Four hundred ninety‐nine apparent single fiber action potentials (ASFAPs) were analyzed with the individual and mean MCD significantly higher in children with autoimmune myasthenia (p < 0.05). Bootstrapping analysis revealed that MCD upper limits of 39 μs for individual MCD and 24 μs for mean MCD significantly improved specificity (p < 0.05) while maintaining sensitivity of the test in distinguishing definite MG NMJ defect from normal NMJ function.

Discussion

Stim‐JA using revised upper limits may help clinicians avoid the over‐diagnosis of NMJ disorders in children. Stim‐JA is a safe and well‐tolerated method to screen for definite MG in children over 2 years.
Harnessing Social Media and NGO Collaboration for Advancing Sustainable Ecotourism Policy: A Pathway to Sustainable Tourism Development
Authors: Zada Muhammad , Khan Salman , Zada Shagufta , Dhar Bablu Kumar , Marcão Ricardo
Published: January 2025

Social media has emerged as a powerful catalyst in promoting sustainable tourism development (STD) by raising awareness, attracting tourists, fostering community engagement, and shaping policy decisions, particularly in developing regions like Khyber Pakhtunkhwa (KPK), Pakistan. However, the combined influence of social media usage, non‐governmental organization (NGO) support, and STD remains underexplored. This study, grounded in organizational learning theory, explores how social media and NGO collaboration contribute to ecotourism policy and STD in Pakistan. The socioeconomic framework in Pakistan, particularly in the KPK region, forms the background against which local dynamics shape such processes. A cross‐sectional survey was conducted, collecting data from 482 respondents in the KPK tourism sector, providing valuable insights into the region's socio‐economic context. This survey approach captures diverse stakeholder perceptions within the KPK tourism sector. The findings reveal that social media significantly influences ecotourism policy, advancing STD. Moreover, NGO support (NGS) serves as a crucial moderating factor, enhancing the role of social media in shaping effective ecotourism policies. This research offers valuable insights into leveraging social media and NGO partnerships to promote sustainable tourism practices, presenting practical implications for policymakers, practitioners, and researchers dedicated to advancing STD and environmental sustainability. In particular, this study highlights the infrastructural and technological challenges of applying social media effectively in developing countries. A unique contribution of this study is its focus on social media's role in a developing region—a context largely underrepresented in existing literature.
Institutions and the real effects of private equity buyouts: A meta‐analysis
Authors: Verbouw Jeroen , Meuleman Miguel , Manigart Sophie
Published: January 2025

Research Summary

This study reviews four decades of fragmented and contradictory empirical literature on the real effects of private equity (PE) buyouts on portfolio companies, differentiating between efficiency and growth outcomes. We hypothesize how institutional forces, including regulatory, cognitive, and normative institutions explain heterogeneity in post‐buyout efficiency and growth across time and countries. We argue that competition and population‐level learning have shifted the cognitive frame underlying value creation in buyouts from financial engineering toward operational engineering and strategic entrepreneurship. Using meta‐analysis, we find support for several of our hypotheses using samples from 66 empirical studies across the finance, management, economics, and entrepreneurship disciplines.

Managerial Summary

This study delves into four decades of fragmented private equity (PE) literature to unravel the practical implications for post‐buyout efficiency and growth. Using meta‐analysis, we explore the role of institutional forces—regulatory, cognitive, and normative—in shaping outcomes across diverse temporal and geographical contexts. We observe an overall paradigm shift in PE value creation over time, transitioning from focusing on financial engineering to operational value creation and strategic entrepreneurship. This transformation is driven by heightened competition and widespread population‐level learning. Validating our hypotheses through a thorough examination of 66 empirical studies spanning finance, management, economics, and entrepreneurship disciplines, our findings offer insights for policymakers and practitioners navigating the nuanced landscape of PE buyouts.
Layer‐by‐Layer Assembly of Antibiotic‐Loaded Multilayered Coating on Polyacrylate Scaffold
Authors: Gao Jie , Du Yu‐Kun , Li Man , Che Li‐Ping , Wang Kai , Feng Lin , Cai Hao‐Yuan , Li Shuo‐Qi , Cui Lan‐Yue , Liu Cheng‐Bao , Xi Yong‐Ming
Published: January 2025

Bacteria‐related infection is a significant problem for the implant materials, which would lead to the failure of the implants. Thus, the surface functionalization for the implant with bacterial inhibition properties would be urgently needed. However, surface inertness and structure complexity are barriers to the surface modification of the 3D‐printed polymer implant. For this reason, the efficiency of antibiotic‐loaded polyelectrolyte multilayers on 3D‐printed resin is investigated. The obtained samples are characterized by various techniques. Antimicrobial test results show that a 99.9% eradication rate against Staphylococcus aureus (S. aureus) could be achieved by antibiotic‐loaded samples. However, the cytocompatibility test shows that the samples also exhibit mild cytotoxicity due to the rapid release of gentamicin sulfate (GS); thus, further work is needed to reduce the side effects of the antibiotics.
Design and Synthesis of Alpha Glycosidase Inhibitors for 1‐Benzyl‐4‐oxa‐1,9‐diazaspiro[5.5]undecan‐2‐one as an Antidiabetic Agent
Authors: Adarasandi Ravi , Gundla Rambabu , Paidikondala Kalyani , Putta Prashanthi , Lakkoju Babi , Kolli Balakrishna
Published: January 2025

A series of (4‐(trifluoromethyl)benzyl)‐linked 1,9‐diazaspiro[5.5]undecane derivatives were designed as α‐glucosidase inhibitors. We have synthesized new (4‐(trifluoromethyl)benzyl)‐linked 1,9‐diazaspiro derivatives for their antidiabetes properties. The newly synthesized compounds were examined for their inhibition activity against α‐glucosidase. The findings demonstrated that the novel synthesized compounds inhibited significantly against α‐glucosidase. Among them, SPO‐7 and SPO‐9 demonstrated the most potent inhibition, with IC50 values of 49.96 and 63.15 nmol, respectively. Docking studies examined the orientation, interaction, and verification of the intent compounds on the active site of α‐glucosidase. The compounds SPO‐7 and SPO‐9 exhibit the highest docking energies, with values of −10.7 and −10.6 kcal/mol, respectively. In addition, the compound SPO‐7 exhibited substantial inhibition effects at all tested concentrations and their capacity to inhibit the bacterial activity against Escherichia coli and Bacillus cereus. The minimum inhibitory concentration (MIC) values for SPO‐7 and SPO‐11 were determined to be 0.156 mg/mL. Furthermore, computational drug‐likeness/ADME/toxicity tests were conducted on the compounds, which indicated that this compound exhibits drug‐like properties and possesses favorable ADME and toxicity profiles.
High‐Entropy Oxychalcogenide for Hydrogen Spillover Enhanced Hydrogen Evolution Reaction in Proton and Anion Exchange Membrane Water Electrolyzers
Authors: Jo Seunghwan , Shin Ki Hoon , Kim Eunmin , Sohn Jung Inn
Published: January 2025

The hydrogen spillover phenomenon provides an expeditious reaction pathway via hydrogen transfer from a strong H adsorption site to a weak H adsorption site, enabling a cost‐efficient hydrogen evolution reaction (HER) analogous to platinum with moderate H adsorption energy. Here, a high‐entropy oxychalcogenide (HEOC) comprising Co, Ni, Mo, W, O, Se, and Te is prepared by a two‐step electrochemical deposition for hydrogen spillover‐enhanced HER in acidic and alkaline water electrolysis. The anodic–cathodic reversal current enables the co‐deposition of cations and aliovalent anions, facilitating a glass structure with multiple active sites for hydrogen spillover. The HEOC exhibits low overpotentials of 52 and 57 mV to obtain a current density of 10 mA cm−2 in acidic and alkaline media, respectively, and long‐term stability for 500 h. The electrochemical and analytical approaches elucidate the hydrogen transfer toward Mo/W−O sites in both acid and alkaline HERs. Meanwhile, the other sites act as hydrogen adsorption or water dissociation‐derived hydroxide adsorption sites, showing accommodable behavior in acidic and alkaline media. The HEOC exhibits a practically high current of 1 A cm−2 at cell voltages of 1.78 and 1.89 V and long‐term stability for 100 h in proton and anion exchange membrane water electrolyzers, respectively.
Enhanced water‐induced shape memory and swelling characteristics of graphene oxide‐cellulose nanofiber reinforced polyvinyl alcohol nanocomposites
Authors: Thomas Lince Mathew , Sreekanth M. S
Published: January 2025

An efficient water‐induced shape memory polymer (SMP) has been developed by incorporating graphene oxide (GO) and cellulose nanofibers (CNF) into polyvinyl alcohol (PVA) matrix. The resulting PVA/GO‐CNF hybrid nanocomposite films at 1 wt% exhibit synergistic effect with superior water‐induced shape memory performance, with 100% shape recovery within 37 sec. Moreover, these hybrid nanocomposite films at 1 wt% demonstrate superior mechanical strength of 77.9 MPa and an improved glass transition temperature (Tg) of 61.4°C in dry conditions. The synergetic effect of GO and CNF in PVA overcomes the limitations of other PVA‐based SMPs in terms of mechanical properties, dimensional stability, and resistance to excessive swelling. Exposure to water significantly reduces Tg to 24.2°C, as confirmed by DSC analysis, which is attributed to the decrease in hydrogen bonding between PVA and 1 wt% GO‐CNF caused by the swelling and plasticizing effect of water. Consequently, the shape recovery of the PVA/1 wt% GO‐CNF occurs with a switching temperature activation due to the polymer chains' released strain energy. These findings suggest that these hybrid films hold the potential for expanding the applications of SMPs in biomedical and moisture‐responsive application such as soft robotics and smart textiles, where water serves as the primary stimulus.

Highlights

PVA/1 wt% GO‐CNF hybrid film demonstrates 100% shape recovery in 37 sec.

Water immersed PVA/1 wt% GO‐CNF nanocomposites show a reduction in Tg to 24.2°C.

PVA/1 wt% GO‐CNF nanocomposite shows superior mechanical strength in dry conditions.

Shape memory behavior is due to reduction in hydrogen bonding and plasticizing effect.
The genetic consequences of successful reintroduction of wild turkey (Meleagris gallopavo) in Nebraska
Authors: Buchanan Brittaney L. , Olson Magdalena J. , Zink Robert M. , Vázquez‐Miranda Hernán
Published: January 2025

The wild turkey (Meleagris gallopavo) recovered from near extirpation because of protection from unrestricted harvest and from introductions and translocations. In Nebraska, modern turkeys are descendants of introductions of domestic, Eastern, Merriam's, and Rio Grande wild turkeys. Whether introduced birds mated assortatively by plumage traits is unknown, and the effects of restoration efforts on the genetic integrity of the introduced birds are unclear. We analyzed variation in the mitogenome and nuclear genome of 16 turkeys selected to represent each subspecies. Analyses of mitochondrial DNA genomes suggest two clades, Gould's plus Merriam's, and a blended group of Eastern, Osceola and Rio Grande turkeys. Analysis of 58 birds from Nebraska for mtDNA control region sequences, plus birds from museums and domestic stock, did not recover any groupings consistent with subspecies or our mitogenome results. We extracted 8,554 single nucleotide polymorphisms (SNPs) from low‐coverage genomes, which resolved each subspecies albeit with some potential conflicts, but unlike the mtDNA pattern suggested that the Rio Grande was more closely related to individuals thought to represent Merriam's or Gould's subspecies. We designed 12 primers that bracketed subspecies‐specific/autapomorphic SNPs and used variation in these independent gene regions to assess genetic structure in birds from Nebraska, to evaluate genetically the known history of reintroductions. From 8,152 base pairs (bp) in the 12 gene regions flanking the subspecies‐specific/autapomorphic SNPs and after alignment and removal of sites with missing data, we created a data set (5,415 bp, 177 variable) of 57 birds from Nebraska including museum frozen tissue specimens identified to subspecies and 11 domestic birds. Our nuclear data suggested considerable blending of genetic distinctiveness among birds from Nebraska, as predicted by the history of reintroductions. Genetic data thus affirmed that Nebraska turkeys consisted mostly of birds of hybrid origin. The reestablishment of wild turkeys across North America has come at the cost of genetic admixing of originally distinct populations. Whether this is problematic depends on whether the goal of wild turkey management is to retain original genetic distinctiveness or harvestable populations of wild turkey irrespective of their genealogical background.
Exploring the New Croatian Mediation Framework: A Leap Forward or a Setback?
Authors: Brozović Juraj
Published: January 2025

In 2023, Croatia enacted the new Amicable Dispute Resolution Act, aimed at providing a new framework for mediation, negotiation, and similar non-adjudicative amicable dispute resolution methods. Despite its ambitions, the changes were not fully implemented, and the new framework has not been unanimously welcomed by the mediation community. The new legislation causes some concerns, as some of the new inadvertent provisions are unclear, or leave dangerous legal gaps leading to uncertainty, with a negative impact on the further expansion of mediation. This chapter offers a critical overview of these changes.
Annulment of Arbitral Awards Rendered in Albania: Trends and Challenges
Authors: Tafaj Flutura Kola , Çinari Silvana
Published: January 2025

The law no. 52/2023 “On Arbitration in the Republic of Albania”, which regulates domestic and international arbitration seated in Albania, entered into force in 2023, after decades of legal vacuum. The adoption of this law is a very welcome positive step. Firstly, it solves all the problems stemming from the lack of an arbitration law in Albania. Secondly, it comes at a time when the Albanian courts’ backlog is huge, mainly due to judicial reforms. Hence, in these times, the use of alternative dispute resolution mechanisms, including arbitration, assumes particular importance for the business community. One of the main problems solved with the entry into force of the arbitration law is the possibility of challenging arbitral awards, which was previously impossible for domestic and international arbitration awards rendered in Albania, due to the lack of an arbitration law. This chapter aims to focus precisely on the novelties brought by the new arbitration law regarding the annulment of arbitral awards rendered in Albania, whether in domestic or international arbitration. Also, although drafted based on the UNCITRAL Model Law, the Albanian arbitration law is not a verbatim adoption. Several differences exist in the provisions regulating the annulment of arbitral awards. For this reason, this chapter will also focus on the challenges related to the implementation of the provisions on the annulment of arbitral awards in Albania. The aims of this chapter are achieved following an analytical and comparative approach.
WHO, UN, and Sustainable Development Goals: Effective Measures for Prevention of CVD in Developing Economies
Authors: Taubert Kathryn A. , Smith Sidney C.
Published: January 2025

Cardiovascular disease (CVD) is the leading cause of death worldwide. CVD is a noncommunicable disease (NCD), and other major NCDs include cancer, diabetes, and chronic lung disease. These four groups of NCDs (led by CVD) are responsible for approximately three-fourths of all deaths globally. The majority of these deaths, including deaths that occur prematurely, are in low- and middle-income countries where the NCD/CVD death rate has been burgeoning since the latter part of the twentieth century. The World Health Organization (WHO) and the United Nations (UN) recognize that the rapid rise of NCDs represent a major health challenge to global development. This chapter describes the initiatives from these two groups designed to better recognize and treat NCDs and reverse the premature mortality from them. The WHO developed a global strategy for the prevention and control of NCDs with an overarching mortality goal to achieve a 25% relative reduction in risk of premature mortality from NCDs by 2025 (later changed to 2030 in accord with the UN). The UN goal to “ensure healthy lives and promote well-being” is a part of the UN Sustainable Development Goals and has a target to reduce by one-third premature mortality from NCDs by 2030.
COVID-19 Pandemia, Socio-economic Status, Limitations, and Outcomes Observed in the Access to Health Care
Authors: Avendaño Luis Fidel , Canals Mauricio , Nazal Carolina Nazzal , Alonso Faustino
Published: January 2025

The global impact of the SARS-CoV-2 pandemic has symbolized the most serious public health episode since the 1918 influenza pandemic. Although pathogenic factors include host, enviroment, and causal agent, the latter appears typically transcendent. ARN viruses represent the principal future threat. Science rapidly identified the agent and developed vaccines. The easy air viral transmission, mainly from pre-symptomatic and asymptomatic cases, makes ineffective most non-pharmaceutical interventions.

Chile started in March 2020 combating the COVID pandemic. The principal actions were (1) rapid viral diagnosis implementation (RT-PCR); (2) containment measures (mobility restriction in the country and frontiers, educational institutions closure, contact tracing, facemasks use, quarantines); (3) reinforcement of COVID health service attention; (4) prompt adquisition of vaccines.

Among health actions, the vaccination coverage was the main accomplished objective. Their cost is briefly commented. The public-private coordination and the scientific and health collaboration improved the pandemic management.

Despite the decrease in primary health care monitoring of chronic patients due to COVID-19 restrictions, the universal coverage for acute myocardial infarction (Chile, 2005) and the integrated bed system through public-private collaboration of the health system was effective in preventing the increase in case fatality during the pandemic.