bluuebunny/crossref_metadata_2025 huggingface dataset:
Making the invisible visible: Critical discourse analysis as a tool for search engine research
Authors: Morrison Renee
Published: December 2023

Like information science more broadly, search engine research has largely been fragmented into two factions: system‐oriented and user‐oriented studies. This limits our capacity for answering some fundamental questions surrounding an integral—often invisible—part of modern life. Given the “search‐ification” of this life, given an oligopolous global market and an information‐wealthy but attention‐poor audience, methods capable of studying search engines, as well as their relationship with users and society are increasingly necessary. This paper proposes critical discourse analysis (CDA) as an effectual, oft‐overlooked method for search engine research, one capable of interrogating both search engines and their use. The paper outlines CDA, provides examples of its application, and highlights its capacity for progressing our critical understanding of search engines. This developing understanding, evidenced by a review of the literature, suggests that challenges brought by search cannot be resolved by critiquing the power of systems alone. Rather, a reclaiming of today's information infrastructure requires we also illuminate the socio‐political environments of search systems, and the metacognitive, invisible processes pivotal to our communication with them. While power‐analyses of search continue, and some have begun to employ CDA, little recognition exists of this theoretical perspective's capacity for supporting both system‐oriented and user‐oriented studies.
Macrocyclic Sulfur Ligand Stabilized Trans‐Palladium Dichloride Complex: Syntheses, Structure, Chlorine Rotation, and Application in α‐Olefination of Nitriles by Primary Alcohols
Authors: Kumar Sunil , Sharma Ashutosh , Mahala Suman , Gaatha K. , Reddy S. Rajagopala , Rom Tanmay , Paul Avijit Kumar , Roy Partha , Joshi Hemant
Published: December 2023

Herein, we have reported the synthesis of a macrocyclic organosulfur ligand (L1) having a seventeen‐membered macrocyclic ring. Subsequently, the corresponding trans‐palladium complex (C1) of bulky macrocyclic organosulfur ligand (L1) was synthesized by reacting it with PdCl2(CH3CN)2 salt. The newly synthesized ligand and complex were characterized using various analytical and spectroscopic techniques. The complex showed a square planar geometry with trans orientation of two ligands around the palladium center. The complex possesses intramolecular SCH…Cl interactions of 2.648 Å between the macrocyclic ligand and palladium dichloride. The potential energy surface (PES) for the rotational process of C1 suggested a barrier of ~23.81 kcal/mol for chlorine rotation. Furthermore, the bulky macrocyclic organosulfur ligand stabilized palladium complex (C1) was used as a catalyst (2.5 mol %) for α‐olefination of nitriles by primary alcohols. The α,β‐unsaturated nitrile compounds were found to be the major product of the reaction (57–78 % yield) with broad substrate scope and large functional group tolerance. Notably, the saturated nitrile product was not observed during the reaction. The mechanistic studies suggested the formation of H2 and H2O as only by‐products of the reaction, thereby making the protocol greener and sustainable.
Micellular fluorescence resonance energy transfer based fluorescent ratiometric response to hydrocarbon analytes
Authors: Gordon Calum K. , Nass Liselotte , Chan Sanutep , Davis Nathaniel J. L. K.
Published: December 2023

Fluorescence resonance energy transfer (FRET) has been utilised to develop numerous selective and sensitive fluorescent ratiometric sensors. Typically, FRET‐based fluorescent ratiometric sensors rely on chemical interactions between the sensor and analyte to illicit a response, thus unreactive hydrocarbons are a neglected analyte and a source for new sensors. By containing an unbound donor–acceptor system within micelles, energy transfer is enabled by spatial confinement. This offers the potential of a ratiometric response as a hydrocarbon analyte is added. Introducing a hydrocarbon analyte to this system causes micelles to swell, increasing the donor–acceptor distance and thus reducing the amount of observed energy transfer. We present InP/ZnS quantum dot donors interacting with a Nile Red acceptor, confined by cetyltrimethylammonium bromide (CTAB)‐based micelles. We alleviated spatial confinement of the pair within micelles using common laboratory solvents to represent hydrocarbons, (toluene, hexane and octadecene). We constructed calibration curves for each solvent and found effective sensing ranges of 0.009–0.21, 0.008–0.27 and 0.003–0.06 M for toluene, hexane and octadecene, respectively. This study contributes towards the development of new hydrocarbon sensors utilising this new mechanism.
Biodegradation of chloroethene compounds under microoxic conditions
Authors: Ojo Abidemi Oluranti , Castillo Julio , Cason Errol Duncan , Valverde Angel
Published: December 2023

The biodegradation of chloroethene compounds under oxic and anoxic conditions is well established. However, the biological reactions that take place under microoxic conditions are unknown. Here, we report the biostimulated (BIOST: addition of lactate) and natural attenuated (NAT) degradation of chloroethene compounds under microoxic conditions by bacterial communities from chloroethene compounds‐contaminated groundwater. The degradation of tetrachloroethene was significantly higher in NAT (15.14% on average) than in BIOST (10.13% on average) conditions at the end of the experiment (90 days). Sporomusa, Paracoccus, Sedimentibacter, Pseudomonas, and Desulfosporosinus were overrepresented in NAT and BIOST compared to the source groundwater. The NAT metagenome contains phenol hydrolase P1 oxygenase (dmpL), catechol‐1,2‐dioxygenase (catA), catechol‐2,3‐dioxygenases (dmpB, todE, and xylE) genes, which could be involved in the cometabolic degradation of chloroethene compounds; and chlorate reductase (clrA), that could be associated with partial reductive dechlorination of chloroethene compounds. Our data provide a better understanding of the bacterial communities, genes, and pathways potentially implicated in the reductive and cometabolic degradation of chloroethene compounds under microoxic conditions.
Sustainable entrepreneurship: When does environmental compliance improve corporate performance?
Authors: Wesseh Presley K. , Lin Boqiang , Zhang Yixuan , Wesseh Preslyn Sharon
Published: December 2023

Concerted effort to reduce ecological damages requires that the role of enterprises should be extended to incorporate environmental issues into their core business objectives. Despite huge developments in sustainable entrepreneurship research, outcomes of sustainable entrepreneurship uptake remain largely unclear. Drawing on data of Chinese firms, and utilizing fixed effects regression, our paper evaluates the conditions under which compliance with environmental regulation may enable or constrain corporate performance. We find that environmental compliance lowers corporate market performance and improves financial performance at the same time. We also find that the decline in market performance is reversed for large and privately owned enterprises, highlighting the role of firm size and ownership in corporate performance. When distinguishing between market‐ and financial performance, our evidence shows that environmental compliance will most likely improve market performance when enterprise carbon intensity level is low and improve financial performance when enterprise carbon intensity level is high. As we have discussed in our paper, these results have several implications from the point of view of managers, firm stakeholders, and policymakers.
Forensic neuropsychiatric aspects of epilepsy
Authors: Beran Roy G. , Fozdar Manish A.
Published: December 2023

Epilepsy may be associated with automatisms that are classed as ‘insane ‘as they are deemed to have originated within the mind. ‘Sane automatism’ is said to occur from external factors, such as physical trauma, while ‘insane automatism’ is said to be innate to the individual experiencing them. To claim automatism within the context of a criminal matter requires a detailed evaluation of the behavior demonstrated and a questioning of the volitional and purposeful nature of this behavior. It is insufficient to rely upon past behavior in association with these seizures to justify the defense of automatism within a specific event. Epilepsy is often considered to be associated with an increase in violence. Proper epidemiological research, both in long‐term, large population control studies and hospital‐based studies, has suggested that epilepsy, per se, is not associated with an increase in violence when compared to the population at large and controlled for other familial and environmental factors.
Ugi four‐multicomponent reaction based synthesis, in vitro, and in silico enzymatic evaluations of new pyrazino[1,2‐a]indole‐1,4‐dione‐indole‐2‐phenylacetamides as potent inhibitors against α‐glucosidase and α‐amylase
Authors: Ahmadi Shourkaei Fatemeh , Rashidi Ranjbar Parviz , Taslimi Parham , Mahdavi Mohammad
Published: December 2023

In this work, synthesis and evaluation of pyrazino[1,2‐a]indole‐1,4‐dione‐indole‐2‐phenylacetamides 6 a–k as new synthetic anti‐diabetes agents were presented. These compounds were synthesized by a four‐component Ugi reaction without metal catalyst. All synthesized compounds were evaluated against α‐glucosidase and α‐amylase as two important targets in the treatment of diabetes. Approximately, all new compounds 6 a–k were more potent than positive control acarbose against these studied enzymes. The obtained potent compounds against the target enzymes were docked in the active site of the related enzyme. Docking study showed that our new potent compounds as well interacted with key residues of the target enzyme.
Enzymatic Catalysts for Hydroxamic Acid Formation: A Mini‐Review
Authors: Singh Rahul Vikram
Published: December 2023

In recent years, biocatalysts have emerged as crucial tool in organic synthesis, particularly for the production of drug intermediates and precursors, e.g., the synthesis of hydroxamic acids. Traditionally, hydroxamic acids were synthesized using organic chemistry methods. However, with the growing emphasis on sustainable and environment‐friendly practices, the chemical industry has increasingly turned towards green synthesis approaches. The significance of hydroxamic acids in medicinal chemistry has also contributed to the changing trends. Following the approval of certain hydroxamic acids as histone deacetylase (HDAC) inhibitors for cancer treatment by the Food and Drug Administration (US‐FDA), there has been a renewed focus on their synthesis and the development of derivatives with improved properties. As an alternative route, amidases have emerged as promising biocatalysts for hydroxamic acid synthesis through their acyltransferase activity. Recent advancements in the synthesis approaches for hydroxamic acids are reviewed. The biocatalytic routes are explored, emphasizing the use of amidases and their acyltransferase activity. The scope and potential applications of this chemoenzymatic approach in synthesizing various hydroxamic acids and their derivatives are discussed. Such advancements have the potential to revolutionize the production of these important compounds, making the synthesis process more sustainable, efficient, and economically viable.
A case of caffeine intoxication resulting in hypothermia
Authors: Ohno Takanori , Katsuki Shino , Miyamoto Kazuyuki , Kaizaki‐Mitsumoto Asuka , Kanazawa Masashi , Ito Toshitaka , Hayashi Munetaka
Published: December 2023

Key Clinical Message

A 30‐year‐old woman arrived at our hospital with polymorphic ventricular tachycardia and hypothermia. Later, it was found that the cause was an overdose of caffeine exceeding the lethal dose. Although it is common for toxidrome caused by caffeine intoxication to produce hyperthermia, here we report a case of hypothermia.
A rare case of mycotic aortic aneurysm with Clostridium perfringens culture
Authors: Tadayon Niki , Shahsavari Saleh , Yahya Reyhane , Nourmohammadi Delaram , Jadidian Faezeh , Babaei Masoud , Mousavizade Mostafa , Vakili Kimia
Published: December 2023

Key Clinical Message

As only early diagnosis, prompt surgical intervention, and appropriate antibiotic therapy can decrease clostridial MAA mortality rate; keeping in mind a broad differential diagnosis in a patient with sepsis and unusual vascular symptoms is important.

Mycotic aortic aneurysm (MAA) is an infrequent but very consequential condition characterized by the pathological disruption of the aorta due to infection. Clostridium perfringens is a bacterium that falls under the taxonomic classification of the genus Clostridium. Although mycotic aneurysm is often not commonly linked with this infection, there are instances when it may function as a causative agent for MAA. Timely diagnosis and thorough therapeutic techniques, including surgical intervention and quick administration of appropriate antibiotics, can potentially reduce the mortality rate associated with clostridial MAA. In this study, we presented a clinical report detailing the diagnosis of a mycotic aneurysm caused by C. perfringens in the thoracic aorta in a 66‐year‐old male patient with a history of diabetes mellitus and a recent prostate biopsy. Furthermore, we discussed the surgical approach and overall management strategy to address this case.
Sample selection method using near‐infrared spectral information entropy as similarity criterion for constructing and updating peach firmness and soluble solids content prediction models
Authors: Liu Yande , He Cong , Jiang Xiaogang
Published: December 2023

When using near‐infrared (NIR) techniques for analysis, model construction and maintenance updates are essential. When model construction is performed in machine learning, the sample set is usually divided into the calibration set and the validation set. The representativeness of the calibration set and the reasonable distribution of the validation set affects the accuracy of the established model. In addition, when maintaining and updating models, selecting the most informative updated sample not only improves the model prediction accuracy but also reduces sample preparation. In this paper, the spectral information entropy (SIE) is proposed to be used as a similarity criterion for dividing the sample set and use this criterion to select updated samples. The Kennard–Stone (KS) and the sample set portioning based on joint x–y distance (SPXY) methods were used for comparison to verify the superiority of the proposed method. The results showed that the model built after dividing the sample set using the SIE method has good prediction effect compared with KS and SPXY method. When predicting soluble solid content (SSC) and hardness, the prediction determination coefficient (
) was improved by more than 15%, and the root mean square error (RMSE) of prediction was reduced by 50%. In terms of model updating, selecting a small number of updated samples using the SIE method can improve the correlation coefficient (
) to more than 80%, and updated models' prediction accuracy is higher than that of KS and SPXY method. It is confirmed that the SIE method can make the NIR analysis technique more reliable.
Peroxo‐Zr/Hf‐Containing Wells‐Dawson Polyoxometalates for H2O2‐based Homogeneous, Heterogeneous, and Biphasic Oxidation Catalysis
Authors: Sundar Anusree , Maksimchuk Nataliya V. , Ivanchikova Irina D. , Zalomaeva Olga V. , Bajuk‐Bogdanović Danica , Kholdeeva Oxana A. , Ćirić‐Marjanović Gordana , Bassil Bassem S. , Kortz Ulrich
Published: December 2023

Four peroxo‐Zr and Hf containing polyanions, [M2(O2)2(X2W17O61)2]16− (X=P, M=ZrIV (ZrP), HfIV (HfP); X=As, M=ZrIV (ZrAs), HfIV (HfAs) were synthesized and structurally characterized. The structures consist of two monolacunary Wells‐Dawson ions which are connected head‐on via two side‐on peroxo bridges. The four new polyanions are solution‐stable as shown by 31P NMR, Raman and FT‐IR spectroscopic studies. Comparative studies on alcohol oxidation with a solvent‐ and phase‐transfer catalyst‐free biphasic oxidative system with homogeneous and supported‐catalyst were performed and several noteworthy observations in reactivity and selectivity were observed, such as the highly selective ring‐opening oxidation of cyclohexanol to adipic acid. Tetra‐n‐butylammonium salts of ZrP and HfP were also synthesized to study the catalytic activity of the compounds in the homogenous H2O2‐based oxidation of olefins, α,β‐unsaturated carbonyl compounds, and thioethers in organic solvent.
Starfruit‐Shaped Zirconium Metal‐Organic Frameworks: From 3D Intermediates to 2D Nanosheet Petals with Enhanced Catalytic Activity
Authors: Tao Cheng‐an , Wang Beibei , Zhao He , Yang Xuheng , Huang Jian , Wang Jianfang
Published: December 2023

We present the fabrication of a novel Starfruit‐shaped metal‐organic framework (SMOF) composed of zirconium and Tetra(4‐carboxyphenyl)porphine linkers. The SMOF exhibits a unique morphology with edge‐sharing two‐dimensional (2D) nanosheet petals. Our investigation unravels a captivating transformation process, wherein three‐dimensional (3D) shuttle‐shaped MOFs form initially and subsequently evolve into 2D nanosheet‐based SMOF structures. The distinct morphology of SMOF showcases superior catalytic activity in detoxifying G‐type nerve agent and blister agent simulants, surpassing that of its 3D counterparts. This discovery of the 3D‐to‐2D transition growth pathway unlocks exciting opportunities for exploring novel strategies in advanced MOF nanostructure development, not only for catalysis but also for various other applications.
High‐Contrast Photoacoustic Imaging of Localized Cysteine in Orthotopic Breast Cancer Enabled by A Totally‐Caged Methylene Blue Probe
Authors: Xie Si , Li Xipeng , Zeng Qin , Wu Yongbo , Zhang Tao
Published: December 2023

High‐contrast photoacoustic sensing imaging (PASI) was greatly determined by optical absorption changes of the absorbers usually enabled by activatable probes via controllably converting the absorbed electromagnetic energy to ultrasound waves. However, most of current photoacoustic probes still suffer from limited imaging contrast towards specific species because of their small absorption spectral changes in the near infrared (NIR) region. Herein, we developed a methylene blue‐based photoacoustic probe with its NIR optical absorption totally caged, which could afford dramatical “OFF‐to‐ON” absorption transition for high‐contrast photoacoustic imaging towards the localized cysteine. The rationally designed methylene blue‐based probe for cysteine (MB‐Cys) would keep in off state with almost no absorption in NIR region, while upon activated by cysteine through cyclization reaction with acrylates, it would reconstruct the π‐conjugation system to release the free methylene blue with strong absorption centered at 665 nm (>130‐fold enhancement). The unique responsive behavior could enable the PASI for photoacoustic mapping the cysteine in orthotopic breast cancer in a high‐contrast manner. Therefore, this work established an up‐to‐date strategy to originally eliminate the background photoacoustic signal for PASI to accurately monitor cysteine in vivo.
Cyclic Hydrocarbon Frameworks Containing Two Bismuth Atoms: Towards 9,10‐Dibismaanthracene
Authors: Rottschäfer Dennis , Reith Sascha , Schwarzmann Johannes , Tambornino Frank , Lichtenberg Crispin
Published: December 2023

When bismuth atoms are incorporated into cyclic organic systems, this commonly goes along with strained or distorted molecular geometries, which can be exploited to modulate the physical and chemical properties of these compounds. In six‐membered heterocycles, bismuth atoms are often accompanied by oxygen, sulfur or nitrogen as a second hetero‐element. In this work, we present the first examples of six‐membered rings, in which two CH units are replaced by BiX moieties (X=Cl, Br, I), resulting in dihydro‐anthracene analogs. Their behavior in chemically reversible reduction reactions is explored, aiming at the generation of dibisma‐anthracene (bismanthrene). Heterometallic compounds (Bi/Fe, Bi/Mn) are introduced as potential bismanthrene surrogates, as supported by bismanthrene‐transfer to selenium. Analytical techniques used to investigate the reported compounds include NMR spectroscopy, high‐resolution mass spectrometry, single‐crystal X‐ray diffraction analyses, and DFT calculations.
Copper‐Catalyzed Sulfimidation in Aqueous Media: a Fast, Chemoselective and Biomolecule‐Compatible Reaction
Authors: Meeus Eva J. , Álvarez María , Koelman Emma , Pérez Pedro J. , Reek Joost N. H. , de Bruin Bas
Published: December 2023

Performing transition metal‐catalyzed reactions in cells and living systems has equipped scientists with a toolbox to study biological processes and release drugs on demand. Thus far, an impressive scope of reactions has been performed in these settings, but many are yet to be introduced. Nitrene transfer presents a rather unexplored new‐to‐nature reaction. The reaction products are frequently encountered motifs in pharmaceuticals, presenting opportunities for the controlled, intracellular synthesis of drugs. Hence, we explored the transition metal‐catalyzed sulfimidation reaction in water for future in vivo application. Two Cu(I) complexes containing trispyrazolylborate ligands (Tpx) were selected, and the catalytic system was evaluated with the aid of three fitness factors. The excellent nitrene transfer reactivity and high chemoselectivity of the catalysts, coupled with good biomolecule compatibility, successfully enabled the sulfimidation of thioethers in aqueous media. We envision that this copper‐catalyzed sulfimidation reaction could be an interesting starting point to unlock the potential of nitrene transfer catalysis in vivo.
Metal‐Free Synthesis of 2‐Aminobenzothiazoles via I2‐Catalyzed Tandem Cyclization Reaction of Amines and Carbon Disulfide
Authors: Chen Ting , Feng Wei , Yang Ruitong , Chen Shanping , Deng Guo‐Jun
Published: December 2023

Comprehensive Summary

A convenient approach for the construction of 2‐aminobenzothiazoles via I2‐catalyzed tandem cyclization reaction of amines and carbon disulfide has been developed. The present approach starts from simple and readily available starting materials, affording a series of 2‐aminobenzothiazoles in up to 89% yields under metal‐free conditions. In this work, C—H/N—H functionalization was achieved and multiple C‐hetero bonds were successfully constructed in one pot.
Straightforward Synthesis of DFO* ‐ An Octadentate Chelator for Zirconium‐89
Authors: Guarrochena Xabier , Kronberger Julia , Tieber Manuel , Ciesielski Philipp , Mindt Thomas L. , Feiner Irene V. J.
Published: December 2023

DFO* is an octadentate chelator able to form highly stable chelates with Zirconium‐89 (89Zr) for nuclear medicinal applications in Positron Emission Tomography (PET).[1,2] The synthesis of DFO* and its scale‐up remains challenging by reported synthetic protocols. For this reason, we set out to develop a de novo synthesis of a hydroxamate‐containing building block suitable for the coupling to the commercially available DFO (desferrioxamine B, mesylate salt) yielding, after deprotection, the desired chelator DFO* in a more efficient procedure. Highlights of the new synthesis of DFO* reported herein are less synthetic steps and the isolation of the desired product DFO* by using solid phase extraction (SPE), thus avoiding tedious HPLC purification. DFO* is obtained in excellent purity (92‐98 %) and an overall yield of approximately 29 %. In addition, the isolated trifluoroacetic acid (TFA)‐salt of DFO* displays an improved solubility in organic solvents (DMSO, DMF, methanol), which will facilitate its use for the preparation of structurally diverse derivatives suitable for bioconjugation chemistry and the development of 89Zr‐labeled radiotracers.
Naturally Occurring and Widespread Resistance to Bioactive Natural Products
Authors: Tan Bin , Zhang Qingbo , Zhang Liping , Zhu Yiguang , Zhang Changsheng
Published: December 2023

Naturally occurring resistances diminish the effectiveness of antibiotics, and present significant challenges to human health. Human activities are usually considered as the main drivers of the dissemination of antibiotic resistance, however, the origin of the clinical antibiotic resistance can be traced to the environmental microbes, and the clinically relevant resistance determinants have already pre‐existed in nature before the antibiotics come into clinic. In this concept, we present the naturally occurring and widespread resistance determinants recently discovered during the biosynthesis study of bioactive compounds. These widely prevalent resistances in environmental microbes, including antibiotic producers and non‐producers, advance the understanding of the origin of resistance, and provide prediction for the clinically relevant resistance to aid in the rational design of more effective drug analogues to combat resistance.
Efficient sensitivity analysis for biomechanical models with correlated inputs
Authors: Hilhorst Pjotr L. J. , Quicken Sjeng , van de Vosse Frans N. , Huberts Wouter
Published: December 2023

In most variance‐based sensitivity analysis (SA) approaches applied to biomechanical models, statistical independence of the model input is assumed. However, often the model inputs are correlated. This might alter the interpretation of the SA results, which may severely impact the guidance provided during model development and personalization. Potential reasons for the infrequent usage of SA techniques that account for input correlation are the associated high computational costs, especially for models with many parameters, and the fact that the input correlation structure is often unknown. The aim of this study was to propose an efficient correlated global sensitivity analysis method by applying a surrogate model‐based approach. Furthermore, this article demonstrates how correlated SA should be interpreted and how the applied method can guide the modeler during model development and personalization, even when the correlation structure is not entirely known beforehand. The proposed methodology was applied to a typical example of a pulse wave propagation model and resulted in accurate SA results that could be obtained at a theoretically 27,000× lower computational cost compared to the correlated SA approach without employing a surrogate model. Furthermore, our results demonstrate that input correlations can significantly affect SA results, which emphasizes the need to thoroughly investigate the effect of input correlations during model development. We conclude that our proposed surrogate‐based SA approach allows modelers to efficiently perform correlated SA to complex biomechanical models and allows modelers to focus on input prioritization, input fixing and model reduction, or assessing the dependency structure between parameters.
Landscape of N1‐methyladenosin (m1A) modification pattern in colorectal cancer
Authors: Jiang Chunhui , Tian Yuan , Xu Chunjie , Zhang Hao , Gu Lei
Published: December 2023

Background

N1‐methyladenosine (m1A) is a recently identified mRNA modification. However, it is still unclear that how m1A alteration affects the development of colorectal cancer (CRC).

Aims

The landscape of m1A modification patterns regarding tumor immune microenvironment (TIME) in CRC is a lack of knowledge. Thus, this study will utilize the public database to comprehensively evaluate of multiple m1A methylation regulators in CRC.

Methods and results

We retrospectively analyzed 398 patients with CRC and 39 healthy people for negative control, using the The Cancer Genome Atlas (TCGA) database to evaluate m1A modification patterns regarding tumor immune microenvironment (TIME) in CRC. The m1Ascore was developed via principal component analysis. And its clinical value in prognosis of CRC was further explored. Our study revealed 12 key m1A‐related DEGs including CLDN3, MUC2 and CCDC85B which are identified associated with invasion and metastasis in CRC. The most important biological processes linked to weak immune response and poor prognosis were the regulation of RNA metabolism and RNA biosynthesis. Furthermore, we found that compared to patients with low m1A scores, those with high m1A scores had higher percentage, larger tumor burdens, and worse prognosis.

Conclusion

Significantly diverse m1A modification patterns can be seen in CRC. Through its impact on TIME and immunological dysfunction, the heterogeneity of m1A alteration patterns influences the prognosis of CRC. This study provided novel insights into the m1A modification in CRC which might promote the development of personalized immunotherapy strategies.
Model‐Based Dose Selection of Subcutaneous Nivolumab in Patients with Advanced Solid Tumors
Authors: Zhao Yue , Sanghavi Kinjal , Roy Amit , Murthy Bindu , Bello Akintunde , Aras Urvi , Vezina Heather
Published: December 2023

The pharmacokinetics (PK) of intravenous (i.v.) nivolumab is well characterized. A subcutaneous (s.c.) nivolumab formulation with and without recombinant human hyaluronidase PH20 enzyme is being evaluated in CheckMate 8KX (NCT03656718). A model‐based analysis was conducted to characterize the PK of nivolumab s.c. and predict systemic exposures after i.v. and s.c. administration to guide dosing regimen selection for nivolumab s.c. A prior i.v. model was modified to incorporate an s.c. extravascular compartment and estimate the absorption rate constant and bioavailability of nivolumab s.c. Serum concentration–time data from 82 patients treated with nivolumab s.c. 720, 960, or 1,200 mg were pooled with existing i.v. data from multiple studies for model development. Prediction‐corrected visual predictive check (pcVPC) plots assessed the model's performance. Stochastic simulations were conducted to predict exposures for i.v. and s.c. administration. The data were described by a two‐compartment model with time‐varying clearance, zero‐order infusion into the central compartment after i.v. dosing, and first‐order absorption from the extravascular compartment after s.c. dosing. The pcVPC suggested that the model adequately described the observed nivolumab s.c. data. Predicted nivolumab exposures at 1,200 mg s.c. every 4 weeks (q4w) were higher than those at the approved dose of 3 mg/kg i.v. q2w and lower than those at the highest tested safe dose of 10 mg/kg i.v. q2w. Nivolumab PK is well‐characterized using the combined s.c./i.v. population PK model. The model‐based analysis facilitated a comprehensive benefit–risk assessment of nivolumab s.c. and informed selection of 1,200 mg s.c. q4w for phase III evaluation.
Direct Esterification of Alkylcarbamic Acids with Alcohols over CeO2 Catalyst
Authors: Mihara Shogen , Yabushita Mizuho , Nakagawa Yoshinao , Tomishige Keiichi
Published: December 2023

Alkylcarbamic acids, which are easily produced via chemical absorption of CO2 into amines, have a great potential to be substrates for producing value‐added chemicals. In this research, the esterification of various alkylcarbamic acids with alcohols into alkyl N‐alkylcarbamates was demonstrated by using a heterogeneous catalyst as well as the corresponding amine additives. In the model reaction, the esterification of benzylcarbamic acid (BZA‐CA) and methanol (MeOH), the target product of methyl N‐benzylcarbamate was obtained in 64 % CO2‐based yield at 413 K in 12 h over a CeO2 catalyst, which also exhibited good reusability. In this catalytic system, the corresponding amine additive (i. e., benzylamine for BZA‐CA) had the important role in the improvement of CO2‐moiety‐based balance, allowing the precise kinetic study, in contrast to the cases without such additive. The detailed kinetic study on the target catalytic system and control systems suggested that BZA‐CA underwent the esterification by MeOH directly. The current catalytic system using the combination of CeO2 catalyst and corresponding amine additive was also demonstrated to be applicable to the synthesis of alkyl N‐alkylcarbamates from alkylcarbamic acids and alcohols with short, linear alkyl chains (≤C3).
Organoid assessment technologies
Authors: Gu Yuyuan , Zhang Wencai , Wu Xianmin , Zhang Yuanwei , Xu Ke , Su Jiacan
Published: December 2023

Despite enormous advances in the generation of organoids, robust and stable protocols of organoids are still a major challenge to researchers. Research for assessing structures of organoids and the evaluations of their functions on in vitro or in vivo is often limited by precision strategies. A growing interest in assessing organoids has arisen, aimed at standardizing the process of obtaining organoids to accurately resemble human‐derived tissue. The complex microenvironment of organoids, intricate cellular crosstalk, organ‐specific architectures and further complicate functions urgently quest for high‐through schemes. By utilizing multi‐omics analysis and single‐cell analysis, cell‐cell interaction mechanisms can be deciphered, and their structures can be investigated in a detailed view by histological analysis. In this review, we will conclude the novel approaches to study the molecular mechanism and cell heterogeneity of organoids and discuss the histological and morphological similarity of organoids in comparison to the human body. Future perspectives on functional analysis will be developed and the organoids will become mature models.
Beta arrestin‐related signalling axes are influenced by dexamethasone and metformin in vascular smooth muscle cells cultured in high glucose condition
Authors: Soleimani Ali Akbar , Shokri Nafiseh , Elahimanesh Mohammad , Mohammadi Payam , Parvaz Najmeh , Bakhshandeh Masoomeh , Najafi Mohammad
Published: December 2023

Background

Metformin (Met) and dexamethasone (Dexa) are known to reduce blood sugar levels and anti‐inflammatory effects, respectively. Based on the acceleration of atherosclerosis process in diabetes, the β‐arrestin 2 (BARR2) gene and protein expression levels were evaluated in vascular smooth muscle cells (VSMCs) treated with Met and Dexa in high glucose conditions in this study.

Methods and Materials

Human VSMCs were cultured in Dulbecco's Modified Eagle Medium/Nutrient Mixture F‐12 (DMEM‐F12) medium and, were treated with different values of Met (1 mM, 5 mM and 7 mM) and Dexa (10−7 M, 10−6 M and 10−5 M) in 24‐ and 48‐h periods. The BARR2 gene and protein expression levels were identified with RT‐qPCR and western blotting techniques, respectively. The signalling axes were predicted from gene network made using Cytoscape software and, were annotated with Gene Ontology.

Results

The BARR2 gene and protein expression levels reduced in VSMCs treated with Dexa and Met after 24‐ and 48‐h periods. These results were more changed after 48 h. Furthermore, many BARR2‐related signalling axes were found from the network genes.

Conclusion

Met and Dexa suppressed the BARR2 protein and gene expression levels in the VSMCs. Moreover, the gene network suggested some the cellular signalling axes related to BARR2 that may be affected by Met and Dexa.
Rethinking trophic interactions in agricultural landscapes through tracking secondary feeding
Authors: Kheirodin Arash , Sayari Mohammad , Schmidt Jason M.
Published: December 2023

Conservation biological control efforts depend on accurately estimating predator roles in crop fields, and knowledge of plant resources generalist predators utilize in agricultural landscapes. Generalist predators move among habitats to feed on insect prey and some predators feed on plants for non‐prey nutrients. Studying predation with molecular gut content analysis (MGCA), provides estimates of within field frequencies of predation on target pests and alternative prey. However, prey DNA takes time to move through the predator digestive system, so a portion of the observed predation likely occurs in adjacent crops or semi‐natural habitats. Therefore, we tested a strategy to estimate recent secondary feeding to help trace predation back to the source habitat. We selected the diamondback moth and three common predators with different mouthparts: Coccinella septempunctata, Geocoris punctipes, and Pardosa spiders, as model organisms for these proof‐of‐concept experiments. We estimated post‐feeding primary and secondary plant DNA detection time and compared it between these three predators using previously designed Lepidoptera primers and newly designed Brassica‐specific primers. Our results indicate secondary plant feeding detection largely depends on predator mouthparts. While secondary collard DNA detectability half‐life was 5.5 h and remained detectable for up to 30 h for the chewing predator, C. septempunctata, only 4% and 8.3% of G. punctipes and Pardosa spp. individuals, respectively, tested positive for collard DNA. However, more studies are required to confirm this mouthpart‐specific post‐feeding plant DNA detection time. Our feeding trials confirmed the possibility of primary and secondary plant feeding detection for chewing predators. Hence, when crops are not flowering (or anthesis), secondary plant feeding detection can be used to trace chewing predators to source habitats where they consumed sessile prey (e.g., nymphs and sessile adults). Such multitrophic linkage knowledge could unravel the landscape‐wise contribution of predators to pest control services.
CO2 to Cyclic Carbonate: A Mechanistic Insight of a Benign Route Using Zinc(II) Salophen Complexes
Authors: Ramesh Aishwarya , De Sharmistha , Bajaj Sakshi , Das Bidisa , Ray Saumi
Published: December 2023

Zinc(II) Schiff base complexes with different substituents at 5, 5’ positions have been synthesized to study the effect of the electronic environment of the metal towards the cycloaddition reaction between CO2 and epoxide. The complexes have been characterized by FT‐IR, XPS, NMR, electronic spectroscopy, LC–MS, and TGA. We have used density functional theory to study the electronic structure of the Zn(II) complexes and modelled the electronic spectra and the mechanism of catalysis. Results obtained from DFT and LC–MS indicate the dimeric structures for all the complexes except ZnL4. The monomeric ZnL4 has the strongest electron withdrawing group, i. e., −NO2 at 5, 5’ positions along with two labile water molecules attached to the Zn center. The dimeric complexes exhibit good to moderate yield for cycloaddition reaction to styrene carbonate under solvent‐free conditions and a relatively low reaction temperature of 80 °C, with CO2 pressure of ~1 atm. The best yield has been achieved by ZnL4. Different rate‐determining steps are captured by the DFT studies for dimeric and monomeric complexes. Without taking any preventing measure of dimerization by attaching the bulky tBu groups, relatively lesser catalytic amounts of all the complexes have shown yields of cyclic carbonate between 53–74 %, depending on the nature of the substituent present.
Entropy generation in a ciliary flow of an Eyring–Powell ternary hybrid nanofluid through a channel with electroosmosis and mixed convection
Authors: Alshehri Nawal A. , Riaz Arshad , Sikandar Sheraz , Muhammad Taseer
Published: December 2023

Drug delivery systems, where the nanofluid flow with electroosmosis and mixed convection can help in efficient and targeted drug delivery to specific cells or organs, could benefit from understanding the behavior of nanofluids in biological systems. In current work, authors have studied the theoretical model of two‐dimensional ciliary flow of blood‐based (Eyring–Powell) nanofluid model with the insertion of ternary hybrid nanoparticles along with the effects of electroosmosis, magnetohydrodynamics, thermal radiations, and mixed convection. Moreover, the features of entropy generation are also taken into consideration. The system is modeled in a wave frame with the approximations of large wave number and neglecting turbulence effects. The problem is solved numerically by using the shooting method with the assistance of computational software “Mathematica” for solving the governing equation. According to the temperature curves, the temperature will increase as the Hartman number, fluid factor, ohmic heating, and cilia length increase. It is also disclosed that ternary hybrid nanoparticles result in a change in flow rate when other problem parameters are varied, and the same is true for temperature graphs. Engineers and scientists can make better use of nanofluid‐based cooling systems in electronics, automobiles, and industrial processes with the aid of the study's findings.
WRAPPER study: Real‐world effectiveness and tolerability of adjunctive perampanel for people with drug–resistant epilepsy in Hong Kong
Authors: Chan Charlie C. H. , Leung Ho Wan
Published: December 2023

Objective

The Prince of Wales Hospital (PWH) Real‐world Analysis of People with Drug‐Resistant Epilepsy (DRE) on PERampanel (WRAPPER) study assessed effectiveness and tolerability of adjunctive perampanel in people with DRE attending PWH.

Methods

This was a prospective single‐center real‐world observational study involving 70 people with DRE between July 2016 and June 2021. A post hoc analysis after the initial study period of 16 weeks assessed outcomes for an extended period up to 52 weeks.

Results

After 16 weeks, median dose of perampanel was 2 mg (IQR 24 mg). 50% responder rates were 40.0%, 41.5%, and 48.7% at 16, 26, and 52 weeks. Seizure freedom was 12.9%, 20.7%, and 25.6% at 16, 26, and 52 weeks. Monthly seizure frequency reduced from 3.0 (IQR 3.0–6.6) at baseline to 2.0 (IQR 2.0–6.0, p = 0.005) at 16 weeks; 2.0 (IQR 2.0–5.0, p = 0.01) at 26 weeks; and 2.0 (IQR 0.0–4.0, p = 0.018) at 52 weeks. Older age predicted 50% responders (OR 1.08, 95% CI 1.01–1.14, p = 0.048).

At 16 weeks, 51.4% (36/70) had treatment‐emergent adverse effects (TEAEs). Most common was seizure exacerbation at 35.7% (25/70) followed by fatigue at 15.7% (11/70). NPI‐12 and ZBI scores indicated no increase in neuropsychiatric symptoms on perampanel.

Significance

Low‐dose 2–4 mg adjunctive perampanel for people with DRE conferred appreciable improvements in seizure reduction without significant neuropsychiatric adverse effects in the real‐world setting at a tertiary center in Hong Kong and had better antiseizure effect with advancing age.

Plain Language Summary

This real‐world study from Hong Kong found low‐dose perampanel was effective and tolerable for people with drug‐resistant epilepsy. Furthermore, perampanel was also potentially more effective with advancing age.
International Water Quality Guidelines for Polycyclic Aromatic Hydrocarbons: Advances to Improve Jurisdictional Uptake of Guidelines Derived Using The Target Lipid Model
Authors: Tillmanns Angeline R. , McGrath Joy A. , Di Toro Dominic M.
Published: December 2023

A large number of different of polycyclic aromatic hydrocarbons (PAHs) have been found in environmental media, yet water quality guidelines (WQGs) are only available for a small subset of PAHs, limiting our ability to adequately assess environmental risks from these compounds. The target lipid model (TLM) was published over 20 years ago and has been extensively validated in the literature, but it has still not been widely adopted by jurisdictions to derive WQGs for PAHs. The goal of our study was to better align the methods for deriving TLM-based WQGs with international derivation protocols. This included updating the TLM with rescreened data to identify datapoints by which effect concentrations were estimated rather than measured, modernizing the statistics used to generate the hazard concentration, and testing the applicability of a chronic TLM model rather than using the acute-to-chronic ratio. The results show that the acute TLM model did not deviate substantially from the previous iteration, indicating that the model has reached a point of stability after over 20 years of testing and improvements. Water quality guidelines derived directly from a chronic TLM provided a similar level of protection as previous iterations of the TLM. The major advantage of adopting TLM-derived WQGs is the expanded list of PAH WQGs, which will allow a more fulsome quantification of environmental risks and the ability to apply the model to mixtures. Environ Toxicol Chem 2024;43:686–700. © 2023 SETAC
Hepatic Transcriptomic Responses to Ethinylestradiol in Embryonic Japanese Quail and Double-Crested Cormorant
Authors: Jeon Yeon-Seon , Sangiovanni Jonathan , Boulanger Emily , Crump Doug , Liu Peng , Ewald Jessica , Basu Niladri , Xia Jianguo , Hecker Markus , Head Jessica
Published: December 2023

Understanding species differences in sensitivity to toxicants is a critical issue in ecotoxicology. We recently established that double-crested cormorant (DCCO) embryos are more sensitive than Japanese quail (JQ) to the developmental effects of ethinylestradiol (EE2). We explored how this difference in sensitivity between species is reflected at a transcriptomic level. The EE2 was dissolved in dimethyl sulfoxide and injected into the air cell of eggs prior to incubation at nominal concentrations of 0, 3.33, and 33.3 µg/g egg weight. At midincubation (JQ 9 days; DCCO 16 days), livers were collected from five embryos/treatment group for RNA sequencing. Data were processed and analyzed using EcoOmicsAnalyst and ExpressAnalyst. The EE2 exposure dysregulated 238 and 1,987 genes in JQ and DCCO, respectively, with 78 genes in common between the two species. These included classic biomarkers of estrogen exposure such as vitellogenin and apovitellenin. We also report DCCO-specific dysregulation of Phase I/II enzyme-coding genes and species-specific transcriptional ontogeny of vitellogenin-2. Twelve Kyoto Encyclopedia of Genes and Genomes pathways and two EcoToxModules were dysregulated in common in both species including the peroxisome proliferator-activated receptor (PPAR) signaling pathway and fatty acid metabolism. Similar to previously reported differences at the organismal level, DCCO were more responsive to EE2 exposure than JQ at the gene expression level. Our description of differences in transcriptional responses to EE2 in early life stage birds may contribute to a better understanding of the molecular basis for species differences. Environ Toxicol Chem 2024;43:772–783. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.