bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of Thiazole‐Chalcone Hybrid Molecules: Antioxidant, Alpha(α)‐Amylase Inhibition and Docking Studies
Authors: Iqbal Hafsa , Akhtar Tashfeen , Haroon Muhammad , Aktaş Aydın , Tahir Ehsaan , Ehsan Muhammad 
Published: April 2023

AbstractThe molecular hybrid approach is very significant to combat various drug‐resistant disorders. A simple, convenient, and cost‐effective synthesis of thiazole‐based chalcones is accomplished, using a molecular hybrid approach, in two steps. The compound 1‐(2‐phenylthiazol‐4‐yl)ethanone (3) was used as the main intermediate for the synthesis of 3‐(arylidene)‐1‐(2‐phenylthiazol‐4‐yl)prop‐2‐en‐1‐ones (4a–f). Thin layer chromatography was used to testify the formation and purity of all synthesized compounds. Further structural confirmation of all compounds was achievedviadifferent spectroscopic techniques (UV, FT‐IR,1H‐ and13C‐NMR) and elemental analysis. All synthesized compounds were tested for their α‐amylase inhibition and antioxidant potential. The cytotoxic property of compounds was also tested within vitrohaemolytic assay. All tested compounds showed moderate to excellent α‐amylase inhibition and antioxidant activity. All tested compounds are found safe to use due to their less toxicity when compared to the standard Triton X. The molecular docking simulation study of all synthesized compounds was also conducted to examine the best binding interactions with human pancreatic α‐amylase (pdb: 4 W93) using AutodockVina. The molecular docking results authenticated thein vitroamylase inhibition results, i.e., 3‐(3‐Methoxyphenyl)‐1‐(2‐phenylthiazol‐4‐yl)prop‐2‐en‐1‐one (4e) exhibited lowest IC50value 54.09±0.11  μM with a binding energy of −7.898 kcal/mol.
Reflections on the Origin and Early Evolution of the Genetic Code
Authors: Fontecilla‐Camps Juan C. 
Published: April 2023

AbstractExamination of the genetic code (GeCo) reveals that amino acids coded by (A/U) codons display a large functional spectrum and bind RNA whereas, except for Arg, those coded by (G/C) codons do not. From a stereochemical viewpoint, the clear preference for (A/U)‐rich codons to be located at the GeCo half blocks suggests they were specifically determined. Conversely, the overall lower affinity of cognate amino acids for their (G/C)‐rich anticodons points to their late arrival to the GeCo. It is proposed that i) initially the code was composed of the eight (A/U) codons; ii) these codons were duplicated when G/C nucleotides were added to their wobble positions, and three new codons with G/C in their first position were incorporated; and iii) a combination of A/U and G/C nucleotides progressively generated the remaining codons.
Does frailty should stop us now?
Authors: Musumeci Giuseppe , Civera Stefania 
Published: April 2023

Key PointsDespite being increasingly encountered in contemporary real‐world practice, due to a global aging of population, frail patients tend to be excluded from large clinical trials, so the impact of frailty on clinical outcomes is often underestimated.Frailty described by the Hospital Frailty Risk Score is associated with high readmission rate, increased healthcare source utilization and lower percutaneous coronary intervention treatment.Further studies are needed to understand if hospital frailty score could provide a prediction model for adverse outcomes, risk‐benefit assessments of interventions, allowing for goal‐oriented care of patients with STEMI.
Adverse effects of high‐dose gamma irradiation on wheat quality and processing traits
Authors: Rigas Nicholas , Maharjan Pankaj , Partington Debra , McDonald Linda , Walker Cassandra , Bekes Ferenc , Florides Christakis , Panozzo Joe 
Published: April 2023

AbstractBackground and ObjectivesGamma irradiation treatments are an effective option for sterilizing microbes and pests that damage wheat, however irradiation can alter the physical and nutritional properties of foods. In this study seven Australian wheat varieties were subjected to 0, 25, and 50 kGy treatments to examine the influence of high‐dose irradiation on a range of wheat quality traits such as physical processing, protein composition and dough rheology.FindingsThe traits most significantly affected by high doses of irradiation included flour color, unextractable polymeric protein (UPP), dough extensibility, dough resistance to extension, pasting viscosity, and starch damage. Rheological traits in the irradiated samples were adversely affected to such a high extent that they were not deemed suitable for end‐product processing, including baking.ConclusionsHigh‐dose irradiation, applied at 25 and 50 kGy, was shown to negatively impact most wheat quality traits tested. High‐dose irradiation is not recommended for treating wheat if viscoelastic functionality is required for manufacturing of high‐quality products.Significance and NoveltyIrradiation treatments significantly reduced the functionality of wheat quality traits tested. Irradiation significantly affected protein composition and structure, with a substantial reduction to the UPP fraction in wheat varieties tested. This change in protein functionality is likely linked to the decrease in dough viscoelastic properties.
Acute respiratory distress syndrome after spontaneous rupture of a large pulmonary hydatid cyst in a 17‐year‐old male: A case report
Authors: Salimi Mehdi , Assar Shirin , Mohamadzadeh Dena , Kanjorpor Asal 
Published: April 2023

AbstractPulmonary hydatid cysts (PHC) and their complications are still a health concern in endemic countries. Here we described a 17‐year‐old male presented with a large PHC with a spontaneous rupture. He developed acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. He was treated with albendazole, broad‐spectrum antibiotics, and corticosteroids. The patient's general condition did not allow any attempt for surgical resection of the cyst. He was discharged in stable condition after one month and referred to a thoracic surgeon for resection of the cyst. As far as we know ARDS after hydatid cyst rupture was rarely reported, and through this case report we aimed to raise awareness of this possible life‐threatening complication.
Single‐Atom Fe Catalyst for Catalytic Ethane Dehydrogenation to Ethylene
Authors: Yu Xiaogang , Li Guomin , Tao Shenghui , Wang Bin , Liu Ce , Jing Huanwang , Shi Feng , Cui Xinjiang 
Published: April 2023

AbstractThe single atom catalysts (SACs) show unique catalytic performance in heterogeneous reactions owing to unsaturated coordination sites and high metal atom dispersion. Herein, a simple wet impregnation method was utilized to synthetize of Fe−Al2O3 catalysts. The Fourier transformation infrared spectroscopy (FTIR) revealed that abundant OH group attached to the support (Al2O3) surface facilitating formation of isolated Fe single atom. High resolution transmission electron microscope (HR‐TEM) and extended X‐ray absorption fine structure (EXAFS) confirmed the Fe single atom architecture. Fe−Al2O3 (4.5 wt %) performed enhanced stability and activity on ethane dehydrogenation reaction.
Chemo‐Enzymatic One‐Pot Oxidation of Cyclohexane via in‐situ H2O2 Production over Supported AuPdPt Catalysts
Authors: Stenner Alex , Lewis Richard J. , Brehm Joseph , Qin Tian , López‐Martín Ángeles , Morgan David J. , Davies Thomas E. , Chen Liwei , Liu Xi , Hutchings Graham J. 
Published: April 2023

AbstractThe introduction of dopant concentrations of Pt into supported AuPd nanoparticles, when used in conjunction with an evolved unspecific peroxygenase (UPO) from Agrocybe aegerita (PaDa‐I) is demonstrated to offer high efficacy towards the one‐pot selective oxidation of cyclohexane to KA oil (cyclohexanol and cyclohexanone), via the in‐situ synthesis of H2O2. The optimised AuPdPt/TiO2/PaDa‐I system achieves significant improvements over analogous AuPd or Pd‐only formulations or the use of commercially available H2O2, with this attributed to the increased rate of H2O2 production by the chemo‐catalyst, which results from the electronic modification of Pd species via Pt incorporation, upon the formation of trimetallic nanoalloys.
From AuPd Nanoparticle Alloys towards Core‐Shell Motifs with Enhanced Alcohol Oxidation Activity
Authors: Silva Tiago A. G. , Teixeira‐Neto Érico , Borges Laís R. , Neves‐Garcia Tomaz , Braga Adriano H. , Rossi Liane M. 
Published: April 2023

AbstractThe best activity of bimetallic AuPd nanoparticles for alcohol oxidation reaction is usually achieved by adjusting the Au/Pd molar ratio. Herein, alloy AuPd nanoparticles of ∼2.5–3.5 nm, ranging from Au‐rich to Pd‐rich compositions, were synthesized through a sol‐immobilization method. A calcination step under air conditions caused an increase in size up to 5.5 nm, but also driven the segregation of Pd to the surface, which generated an Au rich core with Pd on the shell. At high Pd content, the shell structure is formed by PdO. The catalytic activity of Pd‐rich samples (1 : 1, 1 : 2 and 1 : 4 Au : Pd) for benzyl alcohol oxidation increased ∼4‐fold after calcination. Upon reduction with H2, surface PdO motifs are reduced to Pd that did not dissolve back into the AuPd alloy core, maintaining the metallic Pd shell. The catalytic activity decreased. Therefore, restructuring alloyed AuPd nanoparticles into core‐shell like structures with PdO in the shell is beneficial to the catalytic activity, but reduction of PdO layer was detrimental. These results provide new insights on the optimization of AuPd catalysts, considering not only the Au/Pd molar ratio, but also the importance of PdO, which was not anticipated in the previous literature.
Real‐Time Observation for Dynamic Oscillation during Self‐Assembly and Clearance of Aβ42
Authors: Yao Chun‐Nien , Wu Te‐Haw , Cheng Pin‐Yen , Tsao Yueh‐Chia , Lu Yen‐Fei , Chu Li‐Kang , Chiu Chi‐Cheng , Lin Shu‐Yi 
Published: April 2023

AbstractThe dynamic oscillation implicated in structural heterogeneity during the self‐assembly of amyloid peptide 1–42 (Aβ42) may play a crucial role in eliciting cellular responses. We developed a real‐time monitoring platform to observe an oscillatory non‐equilibrium interaction that dominated the Aβ42 clearance by neuronal cells during interplay with an oscillator (lipopolysaccharide, LPS). Molecular dynamics studies indicated that the electrostatic and hydrophobic segments of LPS involved in the temporary heteromolecular association and slightly decelerated the intrinsic thermally–induced protein dynamics of Aβ42. A bait‐specific intervention strategy could temporarily slow down the self‐propagation of Aβ42 to extend the lifetime of autonomous oscillation and augment Aβ42 clearance of neuronal cells. The lifetime increment of oscillation shows a bait concentration‐dependent manner to reflect the non‐equilibrium binding strength. This relationship may serve as a predictor for Alzheimer's disease drug discovery.
Ratiometric Fluorescence Assay for Pyrophosphate Based on Sulfur Nanodots Decorated Metal‐Organic Frameworks
Authors: Ma Jinzhu , Wang Shuai , Wang Tianle , Ma Jing , Wang Zhenguang 
Published: April 2023

AbstractSelective and sensitive detection of inorganic pyrophosphate (PPi) are of great significance both for clinical applications and fundamental research. In this work, a ratiometric fluorescent probe was developed by decorating a porphyrin‐based metal‐organic framework (PCN‐224) with sulfur nanodots (S‐dots). The red‐fluorescence of PCN‐224 was significantly promoted (more than 6‐fold) by S‐dots through inhibiting molecular motion of porphyrin ligand, which also provided active sites for the detection of Cu2+ and PPi. Cu2+ could selectively quench the red‐fluorescence of PCN‐224 through coordination with porphyrin ligand, and the competition reaction between PPi and Cu2+ resulted in the decomposing of coordination and recovery of red‐fluorescence. The blue‐fluorescence from S‐dots was deemed as effective reference, which provided a built‐in correction in complex environments. Based on these photophysical properties, a ratiometric fluorescence assay was developed for the quantitative detection of Cu2+ and PPi, with a limit of detection of 0.11 and 2.66 μM, respectively. The accuracy and practical applications of assays were also demonstrated by detection in tap water and human serum samples.
Intermolecular Triazene Alkene Cycloaddition via Lewis Base Catalysis: Access to Diverse Trifluoromethylated Pyrazolines
Authors: Peng Shiyong , Zhu Huijuan , Wu Haiyun , Hao Di , Yang Liangliang , Liu Yangyang , Gong Xiaojie , Wei Jianhe , Wang Lei 
Published: April 2023

AbstractA novel approach to chemoselective synthesis of biologically important CF3‐subsituted pyrazolines was developed via a Lewis base catalyzed intermolecular triazene cycloaddition reaction of an array of terminal/internal alkenes with CF3CHN2. This strategy features a catalytic amount of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene, high yields (up to 95 %), wide substrate scope and excellent functional group tolerance (54 examples). Importantly, we preformed scaffold diversification of a panel of known pharmaceuticals, natural products, and bioactive heterocycles to generate the corresponding pyrazoline derivatives with potential broad bioactivities for further development.
Stereochemistry‐activity relationship of ceramide‐induced exosome production to clear amyloid‐β in Alzheimer's disease
Authors: Abdelrasoul Mariam , Yuyama Kohei , Swamy Mahadeva M. M. , Murai Yuta , Monde Kenji 
Published: April 2023

AbstractStereochemistry has a substantial impact on the biological activity of various drugs. We investigated the role of stereochemistry of ceramides in inducing the production of exosomes, a type of extracellular vesicle, from neuronal cells, with a potential benefit in improving the clearance of amyloid‐β (Aβ), a causal agent of Alzheimer's disease. A stereochemical library of diverse ceramides with different tail lengths was synthesized with the purpose of varying stereochemistry (D‐erythro: DE, D‐threo: DT, L‐erythro: LE, L‐threo: LT) and hydrophobic tail length (C6, C16, C18, C24). The exosome levels were quantified using TIM4‐based exosome enzyme‐linked immunosorbent assay after concentrating the conditioned medium using centrifugal filter devices. The results revealed a pivotal role of stereochemistry in determining the biological activity of ceramide stereoisomers, with the superiority of those based on DE and DT stereochemistry with C16 and C18 tails, which demonstrated significantly higher exosome production, without a significant change in the particle size of the released exosomes. In transwell experiments with Aβ‐expressed neuronal and microglial cells, DE‐ and DT‐ceramides with C16 and C18 tails significantly decreased extracellular Aβ levels. The results reported here are promising in the design of non‐classic therapies for the treatment of Alzheimer's disease.
C‐GlycosideSynthesis Enabled by Nickel Catalysis
Authors: Shang Weidong , Shi Rong , Niu Dawen 
Published: April 2023

Comprehensive SummaryC‐Glycosides are critical, naturally occurring products and medicinal candidates, and extensive efforts have been made to explore efficient approaches for creating C‐glycosidic bonds. Transition‐metal‐catalysis, particularly nickel‐catalyzed C‐glycosylation reactions constitute a promising strategy. However, achieving a stereoselective synthesis of α‐ and β‐C‐glycosides has been a long‐standing challenge. To address this problem, a variety of nickel‐mediated strategies have been developed. This review highlights recent developments in the nickel‐catalyzed diastereoselective C‐glycosylation reactions and briefly summarizes the mechanistic understandings of these methods.
Explainability and causability in digital pathology
Authors: Plass Markus , Kargl Michaela , Kiehl Tim‐Rasmus , Regitnig Peter , Geißler Christian , Evans Theodore , Zerbe Norman , Carvalho Rita , Holzinger Andreas , Müller Heimo 
Published: April 2023

AbstractThe current move towards digital pathology enables pathologists to use artificial intelligence (AI)‐based computer programmes for the advanced analysis of whole slide images. However, currently, the best‐performing AI algorithms for image analysis are deemed black boxes since it remains – even to their developers – often unclear why the algorithm delivered a particular result. Especially in medicine, a better understanding of algorithmic decisions is essential to avoid mistakes and adverse effects on patients. This review article aims to provide medical experts with insights on the issue of explainability in digital pathology. A short introduction to the relevant underlying core concepts of machine learning shall nurture the reader's understanding of why explainability is a specific issue in this field. Addressing this issue of explainability, the rapidly evolving research field of explainable AI (XAI) has developed many techniques and methods to make black‐box machine‐learning systems more transparent. These XAI methods are a first step towards making black‐box AI systems understandable by humans. However, we argue that an explanation interface must complement these explainable models to make their results useful to human stakeholders and achieve a high level of causability, i.e. a high level of causal understanding by the user. This is especially relevant in the medical field since explainability and causability play a crucial role also for compliance with regulatory requirements. We conclude by promoting the need for novel user interfaces for AI applications in pathology, which enable contextual understanding and allow the medical expert to ask interactive ‘what‐if’‐questions. In pathology, such user interfaces will not only be important to achieve a high level of causability. They will also be crucial for keeping the human‐in‐the‐loop and bringing medical experts' experience and conceptual knowledge to AI processes.
Anomaly detection for high‐dimensional dynamic data stream using stacked habituation autoencoder and union kernel density estimator
Authors: Zeng Zhixia , Huang Ruohe , Xiao Ruliang , Lin Xinhong , Zhang Shi 
Published: April 2023

AbstractWith the rapid development of communication technology, various complex heterogeneous sensor network applications produce a large number of high‐dimensional dynamic data streams, which results in more difficult to anomaly detection than ever before. So, anomaly detection for high‐dimensional dynamic data streams is of a more and more challenging problem. This paper proposes a novel method for detecting anomalies in high‐dimensional dynamic data streams by utilizing several components. Firstly, it uses a stacked habituation autoencoder with habituation physiological mechanism to detect similarity anomalies more easily and capture feature relationships. Secondly, a union kernel density estimator with micro‐cluster is designed to improve online anomaly detection accuracy by estimating the data density. Lastly, candidate anomaly sets and a delayed processing approach are utilized to cope with conceptual drift and evolution in the data stream, allowing the system to adapt to changes in the data over time. Extensive experiments on four high‐dimensional dynamic data streams of the Internet of Things show that the proposed method is very effective.
Conceptualizing the digital therapeutic alliance in the context of fully automated mental health apps: A thematic analysis
Authors: Tong Fangziyun , Lederman Reeva , D'Alfonso Simon , Berry Katherine , Bucci Sandra 
Published: April 2023

AbstractFully automated mental health apps provide a promising opportunity for increasing access to mental health care and resources. Given this opportunity, continued research into the utility and effectiveness of mental health apps is crucial. Therapeutic alliance (TA) refers to the relationship between a client and a healthcare professional, and has been shown to be an important predictor of clinical outcomes in face‐to‐face therapy. Given the significance of TA in traditional therapy, it is important to explore whether the notion of a digital therapeutic alliance (DTA) in the context of fully automated mental health apps also plays an important role in clinical outcomes. Current evidence shows that the conceptualization of DTA in the context of fully automated mental health apps can be potentially different to TA in face‐to‐face therapy. Thus, a new DTA conceptual model is necessary for comprehensively understanding the mechanisms underpinning DTA for fully automated mental health apps. To the best of our knowledge, this is the first study that qualitatively explored the dimensions of a DTA in the context of fully automated mental health apps. We conducted interviews with 20 users of mental health apps to explore the key dimensions comprising DTA in the context of fully automated mental health apps. We found that although conceptualizations of DTA and TA have shared dimensions, flexibility and emotional experiences are unique domains in DTA. On the other hand, although agreement on goals between a therapist and a client is important in face to face therapy, we found that users can have an alliance with an app without a goal. The importance of goal needs further investigations.
Tilianin alleviates lipid deposition and fibrosis in mice with nonalcoholic steatohepatitis by activating the PPARα/Nnat axis
Authors: Ke Fan , Wu Xu , Zheng Jing , Li Cuihong 
Published: April 2023

AbstractThe understanding and treatment of nonalcoholic steatohepatitis (NASH) are still very limited. This study reports the therapeutic effect of tilianin on mice with NASH and further explores its possible molecular mechanisms. A mice model of NASH was established using low‐dose streptozotocin combined with a high‐fat diet and tilianin treatment. Liver function was assessed by determining serum aspartate aminotransferase and alanine aminotransferase in serum. Interleukin (IL)‐1β, IL‐6, transforming growth factor β1 (TGF‐β1), and tumor necrosis factor α (TNF‐α) levels in serum were determined. Hepatocyte apoptosis was assessed using terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate‐biotin nick end labeling staining. Oil Red O staining and boron dipyrrin staining were used to determine lipid deposition in liver tissues. Masson staining was used to evaluate liver fibrosis, and immunohistochemistry and western blot analysis were used to determine the expression of target proteins. Tilianin treatment significantly ameliorated liver function, inhibited hepatocyte apoptosis, and reduced lipid deposition and liver fibrosis in mice with NASH. The expression of neuronatin (Nnat) and peroxisome proliferator‐activated receptor (PPAR) α was upregulated, whereas that of sterol regulatory element‐binding protein 1 (SREBP‐1), TGF‐β1, nuclear factor (NF)‐κB p65, and phosphorylated p65 was downregulated in the liver tissues of mice with NASH after tilianin treatment. The above effects of tilianin were significantly reversed after Nnat knock‐down, but its effect on PPARα expression was unaffected. Thus, the natural drug tilianin shows potential in treatig NASH. Its mechanism of action may be related to the targeted activation of PPARα/Nnat, thereby inhibiting the activation of the NF‐κB signaling pathway.