bluuebunny/crossref_metadata_2025 huggingface dataset:
Empagliflozin in acute myocardial infarction in patients with and without type 2 diabetes: A pre‐specified analysis of the EMPACT‐MI trial
Authors: Petrie Mark C. , Udell Jacob A. , Anker Stefan D. , Harrington Josephine , Jones W. Schuyler , Mattheus Michaela , Gasior Tomasz , van der Meer Peter , Amir Offer , Bahit M. Cecilia , Bauersachs Johann , Bayes‐Genis Antoni , Chopra Vijay K. , Januzzi James L. , Lopes Renato D. , Ponikowski Piotr , Rossello Xavier , Schou Morten , Zieroth Shelley , Brueckmann Martina , Sumin Mikhail , Bhatt Deepak L. , Hernandez Adrian F. , Butler Javed
Published: December 2024

Aims

In the EMPACT‐MI trial, empagliflozin reduced heart failure (HF) hospitalizations but not mortality in acute myocardial infarction (MI). Contemporary reports of clinical event rates with and without type 2 diabetes mellitus (T2DM) in acute MI trials are sparse. The treatment effect of empagliflozin in those with and without T2DM in acute MI is unknown.

Methods and results

A total of 6522 patients with acute MI with newly reduced left ventricular ejection fraction (LVEF) to <45%, congestion, or both, were randomized to empagliflozin 10 mg or placebo. The primary endpoint was time to first HF hospitalization or all‐cause death. Rates of endpoints with and without T2DM and the efficacy and safety of empagliflozin according to T2DM status were assessed. Overall, 32% had T2DM; 14% had pre‐diabetes; 16% were normoglycaemic; 38% had unknown glycaemic status. Patients with T2DM, compared to those without T2DM, were at higher risk of time to first HF hospitalization or all‐cause death (hazard ratio [HR] 1.44; 95% confidence interval [CI] 1.06–1.95) and all‐cause death (HR 1.70; 95% CI 1.13–2.56). T2DM did not confer a higher risk of first HF hospitalization (HR 1.22, 95% CI 0.82–1.83). Empagliflozin reduced first and total HF hospitalizations, but not all‐cause mortality, regardless of presence or absence of T2DM. The safety profile of empagliflozin was the same with and without T2DM.

Conclusion

Patients with acute MI, LVEF <45% and/or congestion who had T2DM were at a higher risk of mortality than those without T2DM. Empagliflozin reduced first and total HF hospitalizations regardless of the presence or absence of T2DM.
Synthesis, Characterisation, and Catalytic Evaluation of Ru‐ONO Complexes Featuring N‐ and P‐Based Ligands
Authors: Awe Babatunde , Swart Glendin , Erasmus Elizabeth , Malan Frederick P.
Published: December 2024

Nine new ruthenium complexes featuring nitrogen and phosphorus donor ligands were synthesised from a Ru precursor featuring a rigid ONO‐pincer ligand. The choice of nitrogen‐ and phosphorous‐based ancillary ligands was guided by a careful evaluation of their different electronic and steric properties. This evaluation aimed to understand how these ligands, once coordinated, could influence the structural, electronic, and catalytic activity of the corresponding complexes. The range of complexes showed moderate catalytic activity in the transfer hydrogenation of alcohols, with the best performing catalyst achieving 96 % conversion in 1 hour (TON=96, TOF=96 h−1). All complexes were characterised using 1H, 13C, 31P (where applicable) NMR spectroscopy, CHN (microanalysis) and HR‐MS analyses. Single crystal structures were obtained for all nine new complexes, as well two new polymorphs of the precursor complex. Complimentary electrochemical (cyclic voltammetry) and density functional theory (DFT) studies provided additional insights into the structural and electronic properties of the different complexes.
Solvent‐Directed Regioselective Cascade Reaction with Diazo Compounds
Authors: Dong Menghua , Wang Chunan , Li Lewan , Chen Yufan , Zeng Jie , Lv Jian , Liao Jie , Wang Haifeng , Gu Shuangxi , Chen Fener
Published: December 2024

A tandem system comprising cyclization reaction of diazo compound and cross‐coupling of the other one has been developed. This provides facile access to pyrazoles and there derivatives with high levels of regioselectivity in moderate to good yields. This process uniquely utilizes CF3CH2OTf both as a solvent and a catalyst under mild conditions. Mechanistic studies provide insights into the intricate sequence involved in the formation of pyrazoles and further selective cross‐coupling with another diazo compound.
High‐Efficiency and Stable Perovskite Solar Cells Enabled by Halogen‐Free Cosolvent‐Processed Pyrazine‐Based Dopant‐Free Hole Transport Material
Authors: Lakshman Chetan , Kim Hyerin , Cho Bo Hyeon , Song Donghyun , Park Jeonghyeon , Kim Young Yong , Yoon Jinhwan , Jin Sung‐Ho
Published: December 2024

The complex molecular structures of electron donor (D)–acceptor (A) polymers provide a wealth of useful hints for producing high power conversion efficiency (PCE) as hole transport materials (HTMs) in perovskite solar cells (PVSCs). Given the recent improvements in PCE, various features are focused on altering the functionalities of HTMs. In this study, a pyrazine‐based acceptor is fused with two known donors benzodithiophene (BDT) and dithienobenzodithiophene (DTBDT) to synthesize two new D–A type polymers (NBD‐Pyz and NDT‐Pyz) to employ them as dopant‐free HTM in PVSCs. The insertion of pyrazine moiety downshifted the energy levels and enhanced coplanarity for both the HTMs. NBD‐Pyz can significantly lower the trap density and passivate the perovskite layer. More interestingly, the NBD‐Pyz HTM performs better than NDT‐Pyz, exhibiting higher hole mobility and better solubility in 2‐methyl anisole (2MA) and o‐xylene. Moreover, a 2MA/o‐xylene cosolvent‐processed dopant‐free polymeric NBD‐Pyz HTM‐based device achieved a champion PCE of 22.9%. Unlike NDT‐Pyz and Spiro‐OMeTAD‐based PVSCs, the unencapsulated NBD‐Pyz devices were more stable, retaining almost 90% of their initial efficiency after 1000 h. In addition, excellent thermal stability was demonstrated by the resulting PVSCs without encapsulation.

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Towards Better Perovskite Absorber Materials: Cu+ Doping Improves Photostability and Radiation Hardness of Complex Lead Halides
Authors: Ustinova Marina I. , Sarychev Maxim N. , Emelianov Nikita A. , Li Yiqun , Zhuo Yuling , Zheng Tongjun , Babenko Sergey D. , Tarasov Evgeniy D. , Kushch Pavel P. , Dremova Nadezhda N. , Kichigina Galina A. , Rasmetyeva Alexandra V. , Kukharenko Andrey I. , Kiryukhin Dmitry P. , Kurmaev Ernst Z. , Xu Xueqing , Troshin Pavel A. , Frolova Lyubov A. , Zhidkov Ivan S.
Published: December 2024

The partial Pb2+ substitution with Cu+ ions has been thoroughly applied as an approach to produce new absorber materials with enhanced light and radiation hardness required for potential aerospace applications of perovskite solar cells. X‐ray photoelectron spectroscopy revealed that Cu+ ions are partially integrated into the crystal lattice of MAPbI3 on the surface of perovskite grains and induce p‐doping effect, which is crucial for a range of applications. Importantly, the presence of Cu+ enhances photostability of perovskite films and blocks the formation of metallic lead as a photolysis product. Furthermore, we have carried out one of the first studies on the radiation hardness of complex lead halides exposed to two different stressors: γ‐rays and 8.5 MeV electron beams. The obtained results demonstrate that Cu+ doping alters completely the radiation‐induced degradation pathways of the double cation perovskite. Indeed, while Cs0.12FA0.88PbI3 degrades mostly with segregation of δ‐phase of FAPbI3 forming a Cs‐rich perovskite phase, the Cs0.12FA0.88Pb0.99Cu0.01I2.99 films tend to expel δ‐CsPbI3 and produce FA‐rich perovskite phase, which shows impressive tolerance to both γ‐rays and high energy electrons. The beneficial effect of copper ion incorporation on the stability of lead halide perovskite solar cells under light soaking and γ‐ray irradiation conditions has been shown. The discovered possibility of controlling the electronic properties and major materials degradation pathways through minor modification of their chemical composition (e.g., replacing 1% of Pb2+ with Cu+) opens up tremendous opportunities for engineering new perovskite absorber compositions with significantly improved properties for both terrestrial and aerospace applications.

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Post‐Polymerization Strategy via Dual Site Clicking for Synthesizing Intrinsically Cross‐Linkable Semiconducting Polymers
Authors: Lee Jaehoon , Kang Seungju , Lee Eunsoo , Lee Jiyun , Yoon Tae Woong , Kim Min‐Jae , Cho Yongjoon , Xiao Mingfei , Boeije Yorrick , Zhu Wenjin , Yang Changduk , Lee Jin‐Wook , Lee Sungjoo , Zhang Guobing , Sirringhaus Henning , Kang Boseok
Published: December 2024

Crosslinked organic semiconductors have opened the way for various fabrication techniques in the field of organic electronics owing to their three‐dimensional network structure with high solvent resistivity. However, recent efforts to synthesize cross‐linkable semiconducting polymers have been limited by their low molecular weights and yields. In this study, this limitation is overcome by a novel post‐polymerization strategy. A reagent with a cross‐linkable functional group, (3‐mercaptopropyl)trimethoxysilane, is attached to a diketopyrrolopyrrole‐based donor–acceptor copolymer (DPPTT) via thioesterification and para‐fluoro‐thiol reaction, modifying two sites simultaneously. This modification preserves the molecular weight and electrical properties of the original polymers. In addition, the use of click chemistry enables high yield (98%) without any purification. The modified DPPTT demonstrated high resistance to organic solvents (80% retention dipped in 1‐chlorobenzene for 1 h). Exploiting this benefit, an ultrathin flexible array of 100 organic field‐effect transistors fabricated using conventional photolithography showed high‐performance reliability. Thus, this study provides a universal strategy to synthesize versatile polymer semiconductors for practical organic electronics.

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Inherited metabolic epilepsies–established diseases, new approaches
Authors: Tokatly Latzer Itay , Pearl Phillip L.
Published: December 2024

Inherited metabolic epilepsies (IMEs) represent the inherited metabolic disorders (IMDs) in which epilepsy is a prevailing component, often determining other neurodevelopmental outcomes associated with the disorder. The different metabolic pathways affected by individual IMEs are the basis of their rarity and heterogeneity. These characteristics make it particularly challenging to establish their targeted therapies, and many of the IMEs are treated nowadays only symptomatically and supportively. However, owing to immense molecular and genetic progress in the last decades, important features of their pathomechanisms have been elucidated. This has led to advancements in the development of novel diagnostic approaches and specific therapies for a considerable number of these unique disorders. This review provides an overview of the broad approach to the diagnosis and management of IMEs, along with their eminent and new individual treatment options, ranging from dietary therapies and vitamins to enzyme and gene replacement therapies.

Plain Language Summary

Inherited metabolic disorders (IMDs) in which epilepsy is a main symptom are considered inherited metabolic epilepsies (IMEs). It is challenging to develop targeted therapies for IMEs since they are rare and individually different in characteristics. Therefore, many of the IMEs are currently treated only symptomatically. However, scientific progress in the last decades led to the creation of specific treatments for many of these unique disorders. This review provides an overview of the approach to the diagnosis and management of IMEs, including the available newer therapeutic modalities.
Full‐Scale Tests to Characterize the Effect of Framing Action and Slab Continuity on the Collapse Capacity of Composite Frames Under Cyclic Loading
Authors: El Jisr Hammad , Lignos Dimitrios G.
Published: December 2024

This paper presents an experimental study that examined the role of the slab continuity and framing action on the overall hysteretic behavior of a composite‐steel moment resisting frame (MRF) up until incipient collapse using advanced instrumentation. The test frame was subjected to three loading phases including asymmetric cyclic lateral loading representative of ratcheting prior to earthquake‐induced collapse. It is shown that the presence of partially restrained transverse beams as part of the floor system results into additional overstrength at the beam‐to‐column joints due to the development of transverse compressive strains at the slab surface. The primary deteriorating mechanisms of the test frame were local buckling at the bottom flanges of the composite‐steel beams followed by concrete crushing at the slab at a lateral drift demand of 3%–4%. Additional instabilities within the dissipative zones of the beams featured the crack initiation and propagation. However, the axial restraint provided by the slab and the framing action led to the stabilization of the crack growth and the local buckling straightening at the bottom flange of the beams even at lateral drift demands higher than 10% rad. This is due to the development of a compressive axial force that passed through the slab and reached up to about 35% of the axial resistance of the bare steel beam at incipient collapse. It is shown that this force prevents the beam axial shortening within the dissipative zones of the test frame, which contradicts the results from conventional beam‐to‐column connection tests with simplified boundary conditions. The experimental results suggest that controlled slip in the ductile shear studs in shallow composite‐steel beams act as a capping mechanism of the additional strain demands that may arise due to the potential overstrength on the concrete compressive strength from its assumed characteristic value, the slab confinement, and the presence of the transverse beams. Composite‐steel beams under hogging bending were able to sustain about 50% of their peak flexural resistance even at chord rotations exceeding 15% rad due to the stabilization of the local buckling length within the dissipative zone. On the other hand, composite‐steel beams under sagging bending attained a zero flexural resistance at the same rotational demands while not achieving a complete separation due to the developed cracks. Measurements from a digital image correlation system suggest that the strut inclination at the interior joint was about 30% higher than that suggested by current standards due to the slab continuity.
Rocking Spectrum for Cylindrical Structures Subjected to Bidirectional Pulse‐Like Ground Motions
Authors: Zhou Xun , Li Jianzhong , Yin Kangshuai , Guo Junjun
Published: December 2024

In recent years, cylindrical structures free to rock have been exploited in practical engineering. However, their seismic response in three dimensions (3D), greatly sensitive to the parameters that define it, is difficult and time‐consuming to predict. To this end, this study focuses on developing a rocking spectrum, an efficient graphical tool linking seismic rocking response to structural parameters, for seismic response prediction and performance‐based seismic design of cylindrical structures. The development of the rocking spectrum is based on the numerical rocking response of 2500 idealized rigid cylinders excited by 100 sets of synthetic bidirectional pulse‐like ground motions. The minimum Redundancy Maximum Relevance (mRMR) algorithm is first employed to reveal that the rocking response is more related to ground acceleration, ground velocity, and ground displacement when the response is small (close to uplift), intermediate, and large (close to overturning), respectively. Following these relations, the support vector machine (SVM) algorithm is employed to develop the rocking spectrum. The obtained rocking spectrum can reliably predict the rocking response of cylinders subjected to the synthetic pulse‐like ground motions. The applicability of the spectrum is also discussed for as‐recorded pulse‐like ground motions.
Saponins Based on Medicinal and Edible Homologous Plants: Biological Activity, Delivery Systems and Its Application in Healthy Foods
Authors: Chen Siwen , Zhou Ying , Li Huiliang , You Lijun , Pedisić Sandra , Shao Ping
Published: December 2024

Medicinal and edible homologous (MEHs) plants are valuable in medicine and food science as edible plants. Saponins, one of the major chemical components isolated from MEHs plants, have significant antioxidant, anti‐inflammatory, antibacterial, and antiviral biological activities. This paper provides an overview of the basic structure, properties, and bioactivity of saponins, the development of novel delivery systems for their enhanced bioavailability, and their applications in various fields. It also highlights the innovations and challenges of current trends in saponin research and provides a basis for the development of a safe and effective natural active ingredient based on MEHs plants. Through comprehensive analysis, this paper aims to provide a theoretical basis and technical support for further research and application of saponins in food science.
Convex Portrait in a Self‐Mirror: Social Dissonance and Social Synthesis
Authors: Caron Jean‐Pierre
Published: December 2024

Social dissonance is both a form of practice, an effect of that practice‐ the furthering of the already present socially dissonant effect/affect‐, and a specific score, proposing possible kinds of action to an audience to bring about the consciousness of their own unfreedom‐ or, more radically, the consciousness of their unconsciousness. But this program has two insufficiencies: 1. The circuit through which the risen consciousness of an unfree state may translate into forms of action is not provided. 2. Even if one has successfully elicited the experience of unfreedom, the transmission of that feeling of unfreedom within a localized social milieu‐ typically enclosed within an art gallery, a concert hall, or a punk venue‐ to the consciousness of the unfreedom of the social world at large is, in the least, problematic. The first insufficiency relates to the problem of the theoretical conditions of practice, or what kinds of influence can a theoretically gained description have upon practice ‐ a very classical problem. The second insufficiency is more specific to Mattin and one would say amounts to the influence one practice may have upon other practices. But this last formulation is a superficial one, being maybe more fruitfully described as the problem of the traction one form of action may have upon the practical conditions of conceptual representation‐ once we understand the dialectics between action and conception that seems to be implicit in Mattin's account, and much of the present text will be dealing with exactly that.
Raisin Production by Convective–Microwave Dryer and Optimization of Ochratoxin A Content, Physicochemical, Sensory Characteristics, and Fungal Load of Raisin
Authors: Behfar Majid , Heshmati Ali , Sharifzadeh Aghil , Taghdir Maryam , Abbaszadeh Sepideh
Published: December 2024

Raisins are so popular in the human diet as a nutritional and sweet snack. The quality of this foodstuff depends on drying conditions. To minimize ochratoxin A (OTA) content and yeast and mold content (YMC) in raisins with favorable physicochemical and sensory properties, the response surface methodology (RSM) and the face‐centered central composite design (FCCD) were utilized. The independent variables were studied over a range of microwave power (0–220 W) and temperature air (35°C–55°C). The microwave power had a significant effect on the OTA value and YMC of dried samples. The use of microwaves in drying contributed to a higher decline in OTA content and YMC than in conventionally dried samples. The regression models detected for OTA content, acidity, pH, rehydration ratio (RR), water holding capacity (WHC), shrinkage, appearance, texture, acceptability, and YMC were significant and reliable. The desirability function was applied to recognize an optimized situation. The result of the RSM analysis showed the optimum conditions for obtaining healthy raisins with desired physicochemical and sensory attributes by microwave‐convective dryer at 220 W microwave power and 38.68°C air temperature.
Proximate Composition, Microbiological Quality and Safety of Raw and Open Sun‐Dried Fish Products in Lake Tana, Ethiopia
Authors: Birie Solomon , Mingist Minwyelet , Kibret Mulugeta , Atlog Tadlo Yitayew , Geremew Hirut , Getnet Banchiamlak
Published: December 2024

The quality and safety of fish products are crucial because poorly handled fish products can result in foodborne illnesses, spoilage, and economic losses. Data on the nutritional and microbiological quality of fish products in Ethiopia, especially in Lake Tana, is limited. This study assessed the proximate composition and microbial quality of raw and open sun‐dried fish products in Lake Tana. Using the standard procedures, 60 fish tissue samples were collected and analyzed for proximate composition and microbial quality. The open sun‐dried fish had significantly higher ash (10.08% ± 1.98%), fat (6.01% ± 1.59%), protein (48.76% ± 8.55%), water activity (0.7358 ± 0.0368) and salt contents (5.89% ± 3.17%) compared to the raw fish (p < 0.05). A significant difference was observed between raw and dried fish in aerobic mesophilic bacteria, Staphylococcus aureus, yeast and mold counts (p < 0.05). The mean total and fecal coliform counts were not significantly different between the raw and dried fish (p > 0.05). In raw fish, 16.6% and 83.3% of samples had total coliforms and fecal coliforms exceeding the recommended limits, respectively. Both raw and dried fish samples tested positive for Salmonella and Shigella spp. There was a strong positive correlation between water activity and microbial load (r = 0.756, p < 0.05) and also between moisture content and microbial load (r = 0.786, p < 0.05). Most of the assessed raw and sun‐dried fish samples were above the international microbial specification limits, which need attention to ensure the safety of fish consumers.
Comprehensive lung microbial gene and genome catalogs assist the mechanism survey of Mesomycoplasma hyopneumoniae strains causing pig lung lesions
Authors: Li Jingquan , Huang Fei , Zhou Yunyan , Huang Tao , Tong Xinkai , Zhang Mingpeng , Chen Jiaqi , Zhang Zhou , Du Huipeng , Liu Zifeng , Zhou Meng , Xiahou Yiwen , Ai Huashui , Chen Congying , Huang Lusheng
Published: December 2024

Understanding the community structure of the lower respiratory tract microbiome is crucial for elucidating its roles in respiratory tract diseases. However, there are few studies about this topic due to the difficulty in obtaining microbial samples from both healthy and disease individuals. Here, using 744 high‐depth metagenomic sequencing data of lower respiratory tract microbial samples from 675 well‐phenotyped pigs, we constructed a lung microbial gene catalog containing the largest scale of 10,031,593 nonredundant genes to date, 44.8% of which are novel. We obtained 356 metagenome‐assembled genomes (MAGs) which were further clustered into 256 species‐level genome bins with 41.8% being first reported in the current databases. Based on these data sets and through integrated analysis of the isolation of the related bacterial strains, in vitro infection, and RNA sequencing, we identified and confirmed that Mesomycoplasma hyopneumoniae (M. hyopneumoniae) MAG_47 and its adhesion‐related virulence factors (VFs) were associated with lung lesions in pigs. Differential expression levels of adhesion‐ and immunomodulation‐related VFs likely determined the heterogenicity of adhesion and pathogenicity among M. hyopneumoniae strains. M. hyopneumoniae adhesion activated several pathways, including nuclear factor kappa‐light‐chain‐enhancer of activated B, mitogen‐activated protein kinase, cell apoptosis, T helper 1 and T helper 2 cell differentiation, tumor necrosis factor signaling, interleukin‐6/janus kinase 2/signal transducer and activator of transcription signaling, and response to reactive oxygen species, leading to cilium loss, epithelial cell‒cell barrier disruption, and lung tissue lesions. Finally, we observed the similar phylogenetic compositions of the lung microbiome between humans with Mycoplasma pneumoniae and pigs infected with M. hyopneumoniae. The results provided important insights into pig lower respiratory tract microbiome and its relationship with lung health.
Predictive Maintenance for UWSNs: A Practical Implementation of Fault Detection Using NDN and Deep Learning
Authors: Benarfa Abdelmadjid , Dahmane Sofiane , Brik Bouziane , Yagoubi Mohamed Bachir
Published: December 2024

Underwater Wireless Sensor Networks (UWSNs) play a critical role in collecting data for various marine applications, but their deployment and maintenance in harsh underwater environments pose significant challenges. Building upon our prior conceptual work, this article presents a practical implementation of an AI‐driven fault detection system for UWSNs, a key component of a future predictive maintenance framework incorporating Named Data Networking (NDN). Using the “Underwater Sensor Dataset,” we implemented a feed‐forward neural network to classify sensor readings as healthy or faulty. The model achieved high accuracy (99.9%), precision (100%), recall (99.1%), and F1‐score (99.6%) on the test set, demonstrating its effectiveness in fault detection. Our findings highlight the feasibility and potential of AI‐based predictive maintenance in UWSNs, even with a simpler neural network model. The framework promises reduced downtime, minimized maintenance costs, and an extended lifespan for UWSNs.
Lysosphingolipid Quantitation in Plasma and Dried‐Blood Spots Using Targeted High‐Resolution Mass Spectrometry
Authors: Ducatez Franklin , Mauhin Wladimir , Ottaviani Jules , Plichet Thomas , Pilon Carine , Lidove Olivier , Barbey Fréderic , Perrichot Régine , Vergnaud Sabrina , Berger Marc G. , Berger Juliette , Belmatoug Nadia , Nadjar Yann , Lamari Foudil , Noel Esther , Marret Stéphane , Bekri Soumeya , Tebani Abdellah
Published: December 2024

Background

Sphingolipidoses are rare inherited metabolic diseases belonging to lysosomal diseases. Early and accurate diagnosis is crucial for effective management and treatment. In this study, we aimed to develop a robust method to accelerate the diagnosis of these sphingolipidoses using dried blood spots and plasma.

Method

We employed high‐resolution mass spectrometry coupled with liquid chromatography (LC‐HRMS) to analyze 6 lysosphingolipids (GlcSph/Psychosine, LysoGb3, LysoSM, LysoSM509, LysoGM1, and LysoGM2) on dried blood spots and plasma samples. The method was used to measure the lysosphingolipid levels in a group of 30 control subjects and 204 samples from patients with sphingolipidoses (61 dB and 143 plasma) including Fabry, Gaucher, GM2 Gangliodosis, Niemann‐Pick type A/B, and Niemann‐Pick type C.

Results

The developed multiplex LC‐HRMS method demonstrated linearity, precision, and quantification performances particularly for GlcSph/Psychosine and LysoGb3 on samples including controls and patients with sphingolipidoses. LysoSM showed recovery variability, wherease LysoGM1 and LysoGM2 showed higher matrix effect.

Conclusion

Our study presents a high‐resolution mass spectrometry method along with the established cutoff values, providing a valuable tool for targeted screening, accurate diagnosis, and monitoring sphingolipidoses. Furthermore, DBS showed reliable results that lay the path to a broader adoption for screening these diseases.
Severe Impact of Omeprazole Timing on pH‐Sensitive Dasatinib Absorption: Unveiling Substantial Drug–Drug Interaction
Authors: Andersson Per , Brisander Magnus , Liljebris Charlotta , Jesson Gérald , Lennernäs Hans
Published: December 2024

The absorption and bioavailability of most tyrosine kinase inhibitors are affected by gastrointestinal pH as they are weak basic lipophilic drugs. Hence, concomitant use of acid reducing agents (ARAs) is frequently restricted. Particularly comedication of crystalline dasatinib (Sprycel) and proton‐pump inhibitors (PPIs) should be avoided. Drug–drug interaction (DDI) studies with PPIs report approximately 40%‐80% bioavailability reduction of dasatinib. Limitations in the design of these studies do not allow for assessing the near maximum DDI as timing of PPI dosing was either not reported or 22 h prior to dasatinib intake. We conducted a DDI study of crystalline dasatinib and omeprazole in healthy, fasted participants, investigating the impact of PPI comedication on dasatinib plasma exposure at a time point when the near maximum DDI effect is expected. Participants were administered omeprazole (day 2‐5) to reach steady state. On day 6, a single dose of crystalline dasatinib was given. Crystalline dasatinib dosing alone on day 1 served as control (single dose). The dosing interval between omeprazole administration and crystalline dasatinib was 10 h (median [range: 9‐10 h]). Dasatinib Cmax and AUC0‐24 were reduced by 96% and 89% by omeprazole comedication. Cmax was 224.6 ± 104.7 ng/mL (mean ± SD) and 8.0 ± 4.5 ng/mL (P < .0001) and AUC0‐24 was 797.6 ± 274.5 and 90.6 ± 38.1 h·ng/mL (P < .0001) without and with omeprazole. T1/2 was 5.7 ± 1.5 h (mean ± SD) with crystalline dasatinib dosing alone and could not be reliably calculated with comedication. To ensure optimal patient outcome, it is vital to investigate bioavailability of pH‐sensitive drugs at the maximal DDI effect of ARAs to understand the worst‐case influence for efficient clinical management.
Microscopic Observation and Physicochemical Analysis Reveal the Microstructure and Chemical Composition of Abelmoschus manihot Flower and Its Potential Value in Anti‐Caries Applications
Authors: Sun Zenghong , Wang Linyang , Chen Pin , Tian Shuge , Chen Yan
Published: December 2024

Abelmoschus manihot flower (AMF), commonly cultivated in Southern China, is homology of medicine and food. In this study, microscopic observation revealed the microstructure of AMF, including upper epidermal cells and nonglandular hairs that play roles in defense and water management. Physicochemical analyses indicated that AMF powder exhibits weak acidity and low moisture content, suggesting its stability. Further fluorescence and spectroscopic analyses identified a diverse array of chemical constituents in AMF, including various flavonoids. Using ultra high performance liquid chromatography_quadrupole exactive hybrid mass spectrometer (UHPLC‐Q Exactive HFX) technology, a total of 407 compounds were identified in AMF, 79 of which were found to have a relative content exceeding 0.1%. A network pharmacological analysis identified 31 potential active components and delineated 10 core targets associated with dental caries. Molecular docking studies demonstrated that the selected active components exhibited strong binding affinities with the aforementioned core targets, particularly flavonoids such as quercetin and morin. In conclusion, this study provides a comprehensive analysis of AMF's microstructure and chemical composition, establishing a scientific foundation for its applications in the pharmaceutical and food industries, as well as in oral health for caries prevention, while also exploring its potential mechanisms of action.
A Comparative Study of Near‐Surface Wind Speed Observations and Reanalysis Datasets in China Over the Past 38 Years
Authors: Mi Xiyuan , Liu Peng
Published: December 2024

Near‐surface wind speed (NSWS) reanalysis products have been widely used in NSWS research, yet there is a lack of evaluation for NSWS reanalysis products. Based on the 10 m wind speed observations data from stations during 1980–2017, this article evaluated the climatic characteristics of NSWS over mainland China at various spatiotemporal scales using four reanalysis datasets: ERA5, MERRA‐2, NCEP‐2 and JRA‐3Q. Compared with station observations, ERA5 and NCEP‐2 showed positive biases in the climatology of NSWS, MERRA‐2 showed negative biases and JRA‐3Q showed significantly negative biases. Regarding the spatial distribution of the climatology, ERA5 performed the best with a spatial correlation coefficient of 0.55 with stations. At the interannual scale, ERA5 showed the best performance with a correlation coefficient of 0.68 with stations, significantly better than the other three reanalysis datasets. At the interdecadal scale, MERRA‐2, NCEP‐2 and JRA‐3Q can generally reproduce the decreasing trend in NSWS from 1980 to 2011. However, none of the four reanalysis datasets can capture the increasing trend from 2011 to 2017. In terms of the annual cycle, only ERA5 can well reproduce the seasonal characteristics in different regions, including the maximum NSWS in the north and the Qinghai–Tibet Plateau in spring and the south of the Yangtze River in summer. Considering the evaluation results at different spatiotemporal scales, ERA5 exhibited good performance regarding the spatial distribution of climatology, interannual variability and annual cycle, but failed to reproduce observational features at the interdecadal scale. JRA‐3Q showed significant advantages in terms of interdecadal variability, whereas neither MERRA‐2 nor NCEP‐2 showed prominent advantages in various aspects.
Increasing Safe Harbor Agreement enrollment: a choice experiment approach to investigate preferred contract attributes
Authors: Rubino Elena C. , Messick Jared A. , Serenari Christopher
Published: December 2024

Safe Harbor Agreements (SHAs) are one of the voluntary incentive programs designed to neutralize some of the costs and burdens associated with endangered species protection on private lands under the Endangered Species Act. They have demonstrated mixed success in terms of landowner participation, indicating that merely offering an SHA is not enough to persuade landowners to enter into agreements with government entities to protect endangered species. Yet little research has investigated landowner decision‐making and the programmatic structures that influence participation in SHAs. In this study, we employed hypothetical choice experiment offerings of Houston toad (Bufo houstonensis) SHAs to explore the reasoning behind Texas landowners' (n = 956) willingness to participate in the program, and to reveal programmatic characteristics most appealing to landowners. Respondents were most frequently willing to enroll in an SHA because of beliefs about and a sense of responsibility towards conserving nature, and were unwilling to potentially enroll in an SHA because they did not know enough about SHAs, did not want the government involved in their land management, and did not want to enter a binding agreement regarding endangered species. Additionally, respondents were more likely to enroll in hypothetical SHAs if the agreements included 10‐year contract durations and full future assurances, and less likely to enroll if they included 30‐year contract durations. This study provides program administrators with insights into how to improve the design and delivery of SHAs to increase participation among private landowners.
Influence of the Sex of Translocation Carrier on Clinical Outcomes of Couples Undergoing Preimplantation Genetic Testing
Authors: Zhang Zhiping , Chen Jiayao , Zhang Lei , Wei Ruiyang , Liu Zhen , Zhao Dunmei , Bi Xingyu , Liang Lixia , Zhang Xueluo , Su Dan , Wu Xueqing
Published: December 2024

Introduction

This study investigated the impact of the carrier on transferable blastocyst rate and live birth outcomes in couples with structural chromosomal abnormalities.

Methods

Couples were grouped into reciprocal translocation, Robertsonian translocation, or inversions groups, and clinical data were retrospectively analyzed. Preimplantation genetic testing for chromosomal structural rearrangements (PGT‐SR) was conducted, and pregnancy outcomes were compared.

Results

Embryo euploidy rates between male and female carriers differed nonsignificantly in the reciprocal translocation and inversion groups but significantly among the three groups. In the Robertsonian translocation group, male carriers had a higher embryo euploidy rate than that of female carriers. Sperm density of male carriers with reciprocal and Robertsonian translocation was significantly lower than that of the female carrier in the same group, whereas the difference was non‐significant in the inversion group. The clinical outcomes of embryo transfer post‐PGT were similar regardless of the sex of carriers with structural chromosomal abnormalities. Female carriers with Robertsonian translocations displayed a higher risk of producing embryos with chromosomal abnormalities than male carriers. Pregnancy, live birth, and cumulative live birth rates following a PGT‐SR cycle were similar, irrespective of chromosomal structural rearrangement type, and carrier sex.

Conclusion

Our findings offer valuable information for genetic counseling.
Copper, Zinc, and Titanium‐Based Semiconductor Nanomaterials for Antimicrobial Coatings and Their Mechanisms
Authors: Manisekaran Ravichandran , Chettiar Aruna‐Devi Rasu , Marasamy Latha , Arthikala Manoj‐Kumar , Kandasamy Ganeshlenin , Ibarra Verónica Campos , Rathore Hanumant Singh
Published: December 2024

Throughout the course of human civilization, numerous disease outbreaks have caused major impacts by affecting the lives of mankind. Currently, excessive and improper use of antimicrobials has led to the emergence of drug‐resistant pathogens, making Antimicrobial Resistance (AMR) a critical global threat, as recognized by the World Health Organization (WHO). If left unaddressed, it will cost approximately USD 100 trillion to the world economy by 2050. Therefore, nanotechnology has emerged as a promising field, offering a wide range of nanomaterials that can be effectively utilized to combat microorganisms. Among these materials, semiconductor nanomaterials (SNMs) have attracted significant attention owing to their exceptional inherent properties that can be effectively employed. Currently, hospital‐acquired infections and infections associated with medical devices pose substantial risks to patients. Consequently, researchers have explored the application of SNMs in the form of antimicrobial coatings or surfaces. This review presents a comprehensive and recent investigation of widely studied SNMs, such as titanium, zinc, and copper‐based, for coating various surfaces (glass, stainless steel, medical devices, textiles, and polymers) and their antimicrobial effects. By preventing or eradicating microbial growth, SNMs have the potential to exert a positive impact, offering a viable solution for coating essential and industrial surfaces.
Efficacy of antiobesity medications for weight reduction in older adults: a systematic review
Authors: Chen Alissa S. , Hajduk Alexandra M. , Grimshaw Alyssa A. , Fried Terri R. , Jastreboff Ania M. , Lipska Kasia J.
Published: December 2024

Objective

The objective of this study was to examine weight reduction and adverse events associated with use of antiobesity medications (AOMs) in older adults ages ≥65 years.

Methods

Seven databases were searched for studies evaluating weight reduction of Food and Drug Administration (FDA)‐approved AOMs. Studies had to include adults ages ≥65 years with obesity (BMI ≥ 30 kg/m2 or ≥27 kg/m2 with one weight‐related condition), with independent analysis of weight reduction for adults ages ≥65 years. Two coauthors extracted and evaluated studies for risk of bias using standardized forms.

Results

Six experimental studies (five secondary analyses of randomized clinical trial data and one single‐arm trial) and two observational studies met inclusion criteria. Seven medications were studied. Sample size of older adults ranged from 13 to 6728. Experimental studies predominantly included patients with concurrent prediabetes or cardiovascular disease. All studies found statistically significant weight reduction between intervention and placebo groups or compared with baseline weight. Few studies reported on adverse events.

Conclusions

Limited evidence suggests weight reduction of AOMs in older adults, with the best current evidence for the use of semaglutide in older adults with obesity and cardiovascular disease. Larger, more inclusive studies of older adults are needed to guide clinical care and determine the tolerability of AOMs for older adults.
Analysis of the Serum MicroRNA Expression Profiles in Patients With Type 2 Diabetic Nephropathy After Simultaneous Pancreas‐Kidney Transplantation
Authors: Liu Luhao , Yu Chaoqun , Zhang Peng , Chen Rongxin , Guo Yuhe , Fang Jiali , Ma Junjie , Li Guanghui , Chen Zheng
Published: December 2024

Background

Simultaneous pancreas‐kidney (SPK) transplantation has become a standard therapy for end‐stage diabetic nephropathy patients. This study aims to investigate serum microRNA (miRNA) profiles in patients with type 2 diabetic nephropathy after SPK and explored the mechanism of insulin resistance induced by relevant miRNAs.

Methods

Patients with type 2 diabetic nephropathy were recruited at our organ transplantation center from June 2018 to March 2019. Six patients were randomly selected, and miRNA microarray analysis was performed to assess serum miRNA expression levels. Target genes were predicted, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted.

Results

The gene chip results revealed significant upregulation of miR‐320d, miR‐4701‐3p, and miR‐940 and significant downregulation of miR‐1229‐5p, miR‐125a‐3p, miR‐3614‐5p, miR‐6090, and miR‐6893‐5p. Target gene prediction and pathway analysis revealed that four miRNAs (miR‐125a‐3p, miR‐320d, miR‐940, and miR‐1229‐5p) form distinct signal regulatory networks.

Conclusion

Specific miRNA expression profiles are present in the serum of patients with diabetic nephropathy after simultaneous pancreas‐kidney transplantation. These specific miRNAs may be involved in the regulatory mechanism of restoring normoglycemia in diabetic nephropathy patients.
Cellulose‐Based Transparent Superhydrophobic Coatings With a Four‐Layer “Armor” Structure for Anti‐Fouling and Anti‐Icing Applications
Authors: Deng Li , Zhang Weiliang , Zhang Tiantian , Huang Yawen , Hu Chengyao
Published: December 2024

A superhydrophobic transparent coating effectively inhibits icing and promotes self‐cleaning, rendering it exceptionally valuable for practical applications in solar panels and car windows. However, attaining both hydrophobicity and transparency in superhydrophobic coatings continues to pose a significant challenge. Thus, this study introduces an innovative four–layered structure. The bottom layer was treated with hyperbranched epoxy–oligosiloxane nanocluster (HP) to serve as a binder. The intermediate layer was modified with amino–silane–modified nano–cellulose (APT–CNF) to develop a micro–scale skeletal structure. The granular layer incorporated fluorine‐modified dendritic silica nanochains (FNPs) to induce nano–structural roughness, while the surface layer employed a silicon elastomer polymer (BFVSE) as an armor‐protective coating featuring both micro– and nano–structural characteristics. The coating exhibits remarkable superhydrophobic properties, with a CA measured at approximately 155°. Furthermore, it demonstrates exceptional light transmittance, reaching approximately 93.1% at a wavelength of 545.5 nm, in contrast to around 91.4% for uncoated glass. The transparent superhydrophobic coating retains its superhydrophobic properties over extended periods following exposure to water impact, sand impact, mechanical bending, high‐temperature heat treatment, acid–base impregnation, and ultraviolet irradiation. Subsequent to dust accumulation testing, the coating continues to exhibit high optical transparency. Its superior performance in solar energy applications, among other fields, indicates significant potential for practical applications.
Dual‐System Collaborative Model of Prosocial Risky Behavior and Cognitive Computation: A Review
Authors: Liu Changlin , Zhao Boqiang , Zhan Youlong , Hu Ping , Mai Xiaoqin
Published: December 2024

Prosocial risky behavior (PRB) refers to actions taken at personal risk for the benefit of others or societal welfare, combining risk‐taking with prosocial intent, and involving the integrated processing of individual risk and social preferences. Building upon the review and evaluation of the definitions of PRB, existing research tools, theoretical models, and neural mechanisms, this paper elucidates the synergistic interaction and mechanisms of the emotional drive and cognitive reasoning systems in PRB. It constructs a dual‐system collaborative model for PRB. Furthermore, to address the shortcomings of existing PRB research tools, such as limited cross‐domain applicability and low reliability, this paper designs a PRB research paradigm within the economic decision‐making domain. Combined with the dual‐system collaborative model of PRB, this paper proposes a cognitive computational modeling concept for PRB and preliminarily verifies its reliability. Future research should conduct cross‐cultural studies, utilizing cognitive neuroscientific technologies, to explore the cultural differences in the mechanisms underlying PRB, thereby enhancing the cross‐cultural interpretive power of the constructed dual‐system collaborative model of PRB. This broadens the theoretical explanatory pathways and research dimensions of PRB.
Factors affecting waiting times to enter opioid use disorder treatment in the United States with a particular focus on potential biological sex disparity
Authors: Nkemjika Stanley , Oforeh Kenneth , Olwit Connie , Olayinka Olaniyi , Tumenta Terence
Published: December 2024

Aim

Opioid use disorder (OUD) is the problematic use of licit or illicit opioids. Thus far, the literature on biological sex differences in accessing treatment is scarce. Hence, we hypothesize that biological sex has a moderating effect on OUD treatment accessibility. We aim to explore biological sex differences in treatment disparities and its role in wait time to enter OUD treatment.

Method

Using the 2018 Treatment Episode Data Set Discharge, the national sample representative of OUD patients in the substance use disorder treatment facilities within the 50 states of the United States was 382,547. Univariate and multivariable logistic analysis of the independent variables and other covariates with the dependent variables were explored to estimate the adjusted odds relationship.

Results

Medications for OUD (MOUD) use among males was significantly different, with waiting 1–7 days (adjusted odds ratio [AOR] = 1.300, 95% confidence interval [CI] = 1.208–1.399) and >7 days (AOR = 0.676, 95% CI = 0.600–0.763) to enter OUD treatment compared to waiting less than a day. For females, MOUD was significantly different, with waiting 1–7 days (AOR = 1.366, 95% CI = 1.244–1.499) and >7 days (AOR = 0.834, 95% CI = 0.721–0.965) to enter OUD treatment compared to waiting less than a day.

Conclusion

Both females and males who received MOUD had lower odds of waiting >7 days to enter treatment than those who received no MOUD. The findings of this study will ensure equity in allocating resources to both males and females.
WATCH: A Workflow to Assess Treatment Effect Heterogeneity in Drug Development for Clinical Trial Sponsors
Authors: Sechidis Konstantinos , Sun Sophie , Chen Yao , Lu Jiarui , Zhang Cong , Baillie Mark , Ohlssen David , Vandemeulebroecke Marc , Hemmings Rob , Ruberg Stephen , Bornkamp Björn
Published: December 2024

This article proposes a Workflow for Assessing Treatment effeCt Heterogeneity (WATCH) in clinical drug development targeted at clinical trial sponsors. WATCH is designed to address the challenges of investigating treatment effect heterogeneity (TEH) in randomized clinical trials, where sample size and multiplicity limit the reliability of findings. The proposed workflow includes four steps: analysis planning, initial data analysis and analysis dataset creation, TEH exploration, and multidisciplinary assessment. The workflow offers a general overview of how treatment effects vary by baseline covariates in the observed data and guides the interpretation of the observed findings based on external evidence and the best scientific understanding. The workflow is exploratory and not inferential/confirmatory in nature but should be preplanned before database lock and analysis start. It is focused on providing a general overview rather than a single specific finding or subgroup with a differential effect.