bluuebunny/crossref_metadata_2025_split huggingface dataset:
Covalent Organic Framework Catalyzed Amide Synthesis Directly from Alcohol Under Red Light Excitation
Authors: Roy Monojit , Mishra Bikash , Maji Shyamali , Sinha Archisman , Dutta Supriti , Mondal Sukanta , Banerjee Abhik , Pachfule Pradip , Adhikari Debashis 
Published: July 2024

AbstractThe dehydrogenative coupling of alcohols and amines to form amide bonds is typically catalysed by homogeneous transition metal catalysts at high temperatures ranging from 130–140 °C. In our pursuit of an efficient and recyclable photocatalyst capable of conducting this transformation at room temperature, we report herein a COF‐mediated dehydrogenative synthesis. The TTT‐DHTD COF was strategically designed to incorporate a high density of functional units, specifically dithiophenedione, to trap photogenerated electrons and effectively facilitate hydrogen atom abstraction reactions. The photoactive TTT‐DHTD COF, synthesized using solvothermal methods showed high crystallinity and moderate surface area, providing an ideal platform for heterogeneous amide synthesis. Light absorption by the COF across the entire visible range, narrow band gap, and valence band position make it well‐suited for the efficient generation of excitons necessary for targeted dehydrogenation. Utilizing red light irradiation and employing extremely low loading of the COF, we have successfully prepared a wide range of amides, including challenging secondary amides, in good to excellent yields. The substrates’ functional group tolerance, very mild reaction conditions, and the catalyst's significant recyclability represent substantial advancements over prior methodologies.
Enabling Modular Click Chemistry Library through Sequential Ligations of Carboxylic Acids and Amines
Authors: Wang Sheng‐Cai , Zhou Xiang , Li Ying‐Xian , Zhang Chun‐Yan , Zhang Zi‐Yan , Xiong Yan‐Shi , Lu Gui , Dong Jiajia , Weng Jiang 
Published: June 2024

AbstractHigh‐throughput synthesis and screening of chemical libraries play pivotal roles in drug discovery. Click chemistry has emerged as a powerful strategy for constructing highly modular chemical libraries. However, the development of new click reactions and unlocking new clickable building blocks remain exceedingly challenging. Herein, we describe a double‐click strategy that enables the sequential ligations of widely available carboxylic acids and amines with fluorosulfuryl isocyanate (FSO2NCO) via a modular amidation/SuFEx (sulfur‐fluoride exchange) process. This method provides facile access to chemical libraries of N‐fluorosulfonyl amides (RCONHSO2F) and N‐acylsulfamides (RCONHSO2NR′R′′) in near‐quantitative yields under simple and practical conditions. The robustness and efficiency of this double click strategy is showcased by the facile construction of chemical libraries in 96‐well microtiter plates from a large number of carboxylic acids and amines. Preliminary biological activity screening reveals that some compounds exhibit high antimicrobial activities against Gram‐positive bacterium S. aureus and drug‐resistant MRSA (MIC up to 6.25 μg ⋅ mL−1). These results provide compelling evidence for the potential application of modular click chemistry library as an enabling technology in high‐throughput medicinal chemistry.
Fabrication of biphasic scaffold composed of bioceramic‐loaded and water‐based photosensitive resins through vat photopolymerization
Authors: Sungkhaphan Piyarat , Kaewkong Pakkanun , Nualplaeng Sunanthiphon , Suannun Titinun , Lertwimol Tareerat , Risangud Nuttapol 
Published: June 2024

AbstractThis study introduces an approach to fabricating a stratified biphasic scaffold using vat photopolymerization. Two different printing materials were employed to prepare the construct, which was composed of polymer composite and hydrogel layers. Bioceramic‐loaded photosensitive resins, which were mainly formulated from poly(ɛ‐caprolactone‐co‐glycidyl methacrylate) (p(ɛ‐CL‐co‐GMA)) and hydroxyapatite (HAp), were introduced as the polymer composite layer. Besides, the water‐based photosensitive resin consisting of polyethylene glycol dimethacrylate (PEGDMA) was utilized to prepare the hydrogel layer. The effect of HAp content in the bioceramic‐loaded resins on the properties of 3D‐printed specimens (e.g., double bond conversion, printing fidelity, mechanical behavior, and morphology) was assessed. The biphasic scaffolds exhibited a compressive strength of approximately 90 MPa. An optical microscope and scanning electron microscope and energy dispersive x‐ray spectrometer (SEM/EDS) analysis were employed to confirm the printing fidelity and the distribution of bioceramics, respectively. Besides, the cytotoxicity result suggested that the biphasic scaffolds were noncytotoxic to articular chondrocytes. We have developed a straightforward strategy using light‐assisted 3D printing to fabricate the biphasic scaffold for further use in biomedical applications.
Functional combination of resveratrol and tamoxifen to overcome tamoxifen‐resistance in breast cancer cells
Authors: Radwan Aliaa M. , Abosharaf Hamed A. , Sharaky Marwa , Abdelmonem Rehab , Effat Heba 
Published: June 2024

AbstractResearchers are encountering challenges in addressing the issue of cancer cells becoming unresponsive to various chemotherapy treatments due to drug resistance. This study was designed to study the influence of antioxidant resveratrol (RSV) to sensitize resistant breast cancer (BC) cells toward tamoxifen (TAM). The cytotoxic effects of RSV and TAM against TAM‐resistant LCC2 cells and their parental michigan cancer foundation‐7 BC cells were determined by sulphorhodamine B assay. Further, the expression levels of multidrug resistance (MDR) genes including ABCB1, ABCC2, ABCG2, and MRP1 using quantitative polymerase chain reaction, apoptosis induction, and reactive oxygen species (ROS) content using flow cytometry were evaluated in either LCC2 cells treated with RSV, TAM, or their combination. The obtained results showed that resistant cells have a magnificent level of MDR genes. This elevated expression dramatically lowered upon receiving the combined therapy of RSV and TAM. Additionally, our work assessed the possible role of RSV in modulating the expression of MDR genes by controlling the expression of certain microRNAs (miRNAs) that target ATP‐binding cassette (ABC) transporters. According to the obtained data, the TAM and RSV combination increased the expression of tumor inhibitor miRNAs such miR‐10b‐3p, miR‐195‐3p, and miR‐223‐3p, which made LCC2 cells more sensitive to TAM. Furthermore, this combination showed an elevation in apoptotic levels and total ROS content. The combination between RSV and TAM could be a functional therapy in the fight against TAM‐resistant BC cells via modulating miRNA and ABC transporters.
Leveraging technology to improve access to medical education in anatomy and physiology in resource‐limited settings: A mixed methods study
Authors: Mora Carpio Andres Leonardo , Romero‐Reveron Rafael , Vasquez Milagros , Bonilla Castillo Jose Antonio , Gaitán Concepción Lucía , Pano Carrera Romina , Liévanos Díaz Diego , Menéndez Conde Benjamín Galván , Montbrun Miryam , Espinoza‐Luna Anabel , Kreiger Joan , Davis John Lucian , Rochester Carolyn , Martin Andres 
Published: July 2024

AbstractThis study assesses the acceptability, appropriateness, feasibility, and efficacy of a novel asynchronous video‐based intervention for teaching respiratory physiology and anatomy to medical students in resource‐limited settings. A series of short video lectures on pleural anatomy, pulmonary physiology, and pathophysiology was created using Lightboard and screen capture technology. These were uploaded to YouTube and Google Drive and made available to 1st‐3rd year medical students at two Latin American universities for 1 week. Employing a parallel‐convergent mixed methods design, we conducted surveys, focus groups, interviews, and pre/post testing for qualitative and quantitative data. Thematic Analysis was used to analyze qualitative data and McNemar's test for quantitative analysis. Seventy‐six students participated. The videos' short format, interactivity, and Lightboard style were highly valued for their flexibility, time efficiency, and educational impact. Students recognized their clinical relevance and trusted their content, suggesting potential applicability in similar settings. Despite infrastructure and connectivity challenges, the use of flexible streaming and downloadable options facilitated learning. Survey results indicated high levels of feasibility (99%), appropriateness (95%), and acceptability (95%), with significant knowledge gains observed (37% correct pre‐test answers vs. 56% post‐test, p < 0.0001). Our findings demonstrate high acceptability, appropriateness, feasibility, and efficacy of a targeted asynchronous education centered on short‐format videos in resource‐limited settings, enabling robust learning despite local barriers. Flexible access is key for overcoming localized barriers. Taking an adaptive, learner‐centered approach to content creation and delivery to address constraints was pivotal to success. Our modular videos could serve as versatile models for flexible education in resource‐constrained settings.
Examining the association between prenatal cannabis exposure and child autism traits: A multi‐cohort investigation in the environmental influences on child health outcome program
Authors: Nutor Chaela , Dickerson Aisha S. , Hsu Tingju , Al‐Jadiri Aseel , Camargo Carlos A. , Schweitzer Julie B. , Shuster Coral L. , Karagas Margaret R. , Madan Juliette C. , Restrepo Bibiana , Schmidt Rebecca J. , Lugo‐Candelas Claudia , Neiderhiser Jenae , Sathyanarayana Sheela , Dunlop Anne L. , Brennan Patricia A. ,   program collaborators for Environmental influences on Child Health Outcomes
Published: July 2024

AbstractThis study examined the association between prenatal cannabis exposure and autism spectrum disorder (ASD) diagnoses and traits. A total sample of 11,570 children (ages 1–18; 53% male; 25% Hispanic; 60% White) from 34 cohorts of the National Institutes of Health‐funded environmental influences on child health outcomes consortium were included in analyses. Results from generalized linear mixed models replicated previous studies showing that associations between prenatal cannabis exposure and ASD traits in children are not significant when controlling for relevant covariates, particularly tobacco exposure. Child biological sex did not moderate the association between prenatal cannabis exposure and ASD. In a large sample and measuring ASD traits continuously, there was no evidence that prenatal cannabis exposure increases the risk for ASD. This work helps to clarify previous mixed findings by addressing concerns about statistical power and ASD measurement.
Simultaneous Inference of Multiple Binary Endpoints in Biomedical Research: Small Sample Properties of Multiple Marginal Models and a Resampling Approach
Authors: Budig Sören , Jung Klaus , Hasler Mario , Schaarschmidt Frank 
Published: July 2024

ABSTRACTIn biomedical research, the simultaneous inference of multiple binary endpoints may be of interest. In such cases, an appropriate multiplicity adjustment is required that controls the family‐wise error rate, which represents the probability of making incorrect test decisions. In this paper, we investigate two approaches that perform single‐step ‐value adjustments that also take into account the possible correlation between endpoints. A rather novel and flexible approach known as multiple marginal models is considered, which is based on stacking of the parameter estimates of the marginal models and deriving their joint asymptotic distribution. We also investigate a nonparametric vector‐based resampling approach, and we compare both approaches with the Bonferroni method by examining the family‐wise error rate and power for different parameter settings, including low proportions and small sample sizes. The results show that the resampling‐based approach consistently outperforms the other methods in terms of power, while still controlling the family‐wise error rate. The multiple marginal models approach, on the other hand, shows a more conservative behavior. However, it offers more versatility in application, allowing for more complex models or straightforward computation of simultaneous confidence intervals. The practical application of the methods is demonstrated using a toxicological dataset from the National Toxicology Program.
Broadening The Substrate Scope of Aldolases Through Metagenomic Enzyme Discovery
Authors: Rizzo Andrea , Aranda Carmen , Galman James , Alcasabas Annette , Pandya Akash , Bornadel Amin , Costa Bruna , Hailes Helen C. , Ward John M. , Jeffries Jack W. E. , Dominguez Beatriz 
Published: July 2024

AbstractBio‐processes based on enzymatic catalysis play a major role in the development of green, sustainable processes, and the discovery of new enzymes is key to this approach. In this work, we analysed ten metagenomes and retrieved 48 genes coding for deoxyribose‐5‐phosphate aldolases (DERAs, EC 4.1.2.4) using a sequence‐based approach. These sequences were recombinantly expressed in Escherichia coli and screened for activity towards a range of aldol additions. Among these, one enzyme, DERA‐61, proved to be particularly interesting and catalysed the aldol addition of furfural or benzaldehyde with acetone, butanone and cyclobutanone with unprecedented activity. The product of these reactions, aldols, can find applications as building blocks in the synthesis of biologically active compounds. Screening was carried out to identify optimized reaction conditions targeting temperature, pH, and salt concentrations. Lastly, the kinetics and the stereochemistry of the products were investigated, revealing that DERA‐61 and other metagenomic DERAs have superior activity and stereoselectivity when they are provided with non‐natural substrates, compared to well‐known DERAs.
Alkoxide Trap in Transition‐Metal‐Catalyzed Dehydrogenative Coupling and Borrowing Hydrogen Reactions
Authors: Vignesh Arumugam , Wang Zhe , Liu Yan , Ke Zhuofeng 
Published: July 2024

AbstractDehydrogenative coupling (DC) and borrowing hydrogen(ation) (BH) reactions are crucial in modern organic synthesis, offering efficient and sustainable ways to create valuable compounds. However, they often face a significant challenge: the alkoxide trap. This Concept explores the alkoxide trap in DC and BH reactions, starting with the basic mechanisms and the role of alkoxide intermediates. It then examines how the alkoxide trap leads to catalyst deactivation and reduced selectivity, influenced by thermodynamic and kinetic factors. To address this, we review recent advances in catalyst design, ligand engineering, and optimized reaction conditions, along with the use of in‐situ spectroscopy and computational modelling, to better understand the underlying processes and guide rational catalyst development. Furthermore, this Concept highlights the broad applicability of DC, and BH reactions across various substrates, underscoring the urgency of addressing the alkoxide trap issue to unlock their full synthetic potential.
Enantioselective Borrowing Hydrogen: A Modern Tool to Construct Enantioenriched Molecules
Authors: Alexandridis Anestis , Quintard Adrien 
Published: July 2024

AbstractIn the quest for the more rapid and eco‐compatible preparation of complex molecules from widely available ones, borrowing hydrogen is one of the most elegant manners to directly functionalize alcohols. Such catalytic cycles reduce the synthetic cost, and avoid waste and additional steps associated with adjusting the redox state for the functionalization of carbon chains. In this field, the last ten years have seen the development of general strategies to control the absolute stereochemistry of the created molecules. This enantiocontrol can arise from the three distinct steps of the catalytic cycle, namely the initial dehydrogenation, carbonyl functionalization or final hydrogen back‐transfer. This review presents the different enantioselective approaches developed according to these principles and highlights the great potential of these transformations, the current limitations and future challenges.
Electrochemical Evaluation of Penta‐Coordinated Fe Phthalocyanine During the Oxygen Reduction Reaction in Various Acidic Solutions
Authors: Zúñiga Loyola César , Troncoso Nicolás , Gatica Caro Angélica , Tasca Federico 
Published: July 2024

AbstractIron phthalocyanine (FePc) was penta‐coordinated with pyridine ligand (Py) grafted on carbon nanotube (CNT), to form (FePc‐Py‐CNT). The complex was studied as a catalyst for the oxygen reduction reaction ORR in seven different supporting electrolytes: OH− (0.1 M), OH− (1 M), NO3− (1 M), HSO4− (1 M), ClO4− (1 M), Br− (1 M), Cl− (1 M), to unveil anion‐poisoning effects and mechanism. Through cyclic voltammetry and polarization curves in N2 and O2 saturated atmospheres, thermodynamic and kinetic data were acquired. In acid media, the formal potential Fe(III)/(II) (E0’Fe(III)/(II)) of the complex is biased to more negative potentials by the anion presence. Similar effects were observed for the onset potential (Eonset) during polarization curves for the ORR. When the ORR was performed in the presence of either ClO4−, or HSO4−, anions, Tafel analysis showed different values depending if were derived from the low or from the high overpotential regions, revealing an inner‐sphere electron transfer mechanism (ISET). The Tafel values derived from measurements in the presence of Cl− and Br− anions do not change when extracted at low or at high overpotentials evidencing an outer‐sphere reaction mechanism (OSET). Gibbs free energies were derived from poisoning tests confirming the ISET and OSET mechanisms. The poisoning effect is responsible for the immediate loss of performance for these catalysts during the ORR in acidic media.
Order‐restricted hypothesis tests for nonlinear mixed‐effects models with measurement errors in covariates
Authors: Zhang Yixin , Liu Wei , Wu Lang 
Published: June 2024

AbstractOrder‐restricted hypothesis testing problems frequently arise in practice, including studies involving regression models for longitudinal data. These tests are known to be more powerful than tests that ignore such restrictions. In this article, we consider order‐restricted tests for nonlinear mixed‐effects models with measurement errors in time‐dependent covariates. We propose to use a multiple imputation method to address measurement errors, since this approach allows us to use existing complete‐data methods for order‐restricted tests. Some theoretical results are presented. We evaluate our proposed methods via simulation studies that demonstrate they are more powerful than either a competing naive method or a two‐step approach to testing hypotheses. We illustrate the use of our proposed approach by analyzing data from an HIV/AIDS study.
Too innovative to be recycled: The role of perceived innovativeness in recycled product advertisements
Authors: Park Taehoon , Kim Junghyun 
Published: July 2024

AbstractWith the advent of various technological advancements, companies can now recycle unique waste materials that would otherwise be dumped into landfills (e.g., coffee grounds) and highlight their engagement in sustainable business practices. Using four scenario‐based experimental studies alongside analyses of variance (ANOVA) and regression methodologies, we investigated the role of perceived recycling innovativeness in consumers' responses to recycled product advertisements. Our results revealed that consumers are less likely to purchase recycled products made from unique waste materials that are considered more innovative compared to products made from typical waste materials. Furthermore, our findings showed that inferences of low quality mediate the negative effect of innovative recycling on purchase intention. This effect was attenuated by consumers' purchase goals and the availability of recycling process information. This work's theoretical contribution is its expansion of knowledge on how consumers infer recycled products' performance based on information about the source materials. Practically, this work offers recommendations on ways to prevent the negative influence of disclosing source materials used in a recycled product.
Autofluorescence lifetime flow cytometry with time‐correlated single photon counting
Authors: Samimi Kayvan , Pasachhe Ojaswi , Guzman Emmanuel Contreras , Riendeau Jeremiah , Gillette Amani A. , Pham Dan L. , Wiech Kasia J. , Moore Darcie L. , Skala Melissa C. 
Published: June 2024

AbstractAutofluorescence lifetime imaging microscopy (FLIM) is sensitive to metabolic changes in single cells based on changes in the protein‐binding activities of the metabolic co‐enzymes NAD(P)H. However, FLIM typically relies on time‐correlated single‐photon counting (TCSPC) detection electronics on laser‐scanning microscopes, which are expensive, low‐throughput, and require substantial post‐processing time for cell segmentation and analysis. Here, we present a fluorescence lifetime‐sensitive flow cytometer that offers the same TCSPC temporal resolution in a flow geometry, with low‐cost single‐photon excitation sources, a throughput of tens of cells per second, and real‐time single‐cell analysis. The system uses a 375 nm picosecond‐pulsed diode laser operating at 50 MHz, alkali photomultiplier tubes, an FPGA‐based time tagger, and can provide real‐time phasor‐based classification (i.e., gating) of flowing cells. A CMOS camera produces simultaneous brightfield images using far‐red illumination. A second PMT provides two‐color analysis. Cells are injected into the microfluidic channel using a syringe pump at 2–5 mm/s with nearly 5 ms integration time per cell, resulting in a light dose of 2.65 J/cm2 that is well below damage thresholds (25 J/cm2 at 375 nm). Our results show that cells remain viable after measurement, and the system is sensitive to autofluorescence lifetime changes in Jurkat T cells with metabolic perturbation (sodium cyanide), quiescent versus activated (CD3/CD28/CD2) primary human T cells, and quiescent versus activated primary adult mouse neural stem cells, consistent with prior studies using multiphoton FLIM. This TCSPC‐based autofluorescence lifetime flow cytometer provides a valuable label‐free method for real‐time analysis of single‐cell function and metabolism with higher throughput than laser‐scanning microscopy systems.