bluuebunny/crossref_metadata_2025_split huggingface dataset:
Length of hysterotomy for fetal spina bifida repair is associated with prematurity risk
Authors: Watananirun Kanokwaroon , Vargas Anna M. L. F. , Vergote Simen , Lewi Liesbeth , Filippo Marcelo O. L. , McCulloch Peter , Devlieger Roland , Peralta Cleisson F. A. , Deprest Jan 
Published: March 2024

AbstractObjectiveTo investigate whether prenatal repair of spina bifida aperta through mini‐hysterotomy results in less prematurity, as compared to standard hysterotomy, when adjusting for known prematurity risks.MethodsWe performed a bi‐centric, propensity score matched, controlled study, that is, adjusting for factors earlier reported to result in premature delivery or membrane rupture, in consecutive women having prenatal repair either through stapled hysterotomy or sutured mini‐hysterotomy (≤3.5 cm). Matches were pairwise compared and cox‐regression analysis was performed to define the hazard ratio of delivery <37 weeks.ResultsOf 346 meeting the MOMS‐criteria, 78 comparable pairs were available for matched‐controlled analysis. Mini‐hysterotomy patients were younger and had a higher BMI. Mini‐hysterotomy was associated with a 1.67‐lower risk of delivery <37 weeks (hazard ratio: 0.60; 95% CI: 0.42–0.85; p = 0.004) and 1.72 for delivery <34 + 6 weeks (hazard ratio: 0.58; 95% CI: 0.34–0.97; p = 0.037). The rate of intact uterine scar at birth (mini‐hysterotomy: 98.7% vs. hysterotomy: 90.4%; p = 0.070), the rate of reversal of hindbrain herniation within 1 week after surgery (88.9% vs. 97.4%; p = 0.180) and the rate of cerebrospinal fluid leakage (0% vs. 2.7%; p = 0.50) were comparable.ConclusionPrenatal spina bidifa repair through mini‐hysterotomy was associated with a later gestational age at delivery and a comparable intact uterus rate without apparent compromise in neuroprotection.
Codesign of Lynch ChoicesTM: Using implementation science to create a clinically deliverable patient decision support website to transform cancer genetics care pathways
Authors: Kohut Kelly , Morton Kate , Turner Lesley , Foster Rebecca ,   the CanGene‐CanVar Patient Reference Panel,   International Lynch Decision Aid Stakeholder Panel, Eccles Diana , Foster Claire 
Published: March 2024

AbstractBackgroundResources including Patient Decision Aids (PtDA) are useful and valued by patients and clinicians to provide information and complement shared decision‐making. Despite their promise, few PtDA exist for patients with genetic cancer susceptibility facing difficult decisions about risk management. We aimed to fill this gap, partnering with patients to codesign Lynch ChoicesTM, a PtDA website for families with Lynch Syndrome. In addition to a Patient Reference Panel, we purposively invited an international stakeholder panel including charities, public bodies, clinical and academic experts. Implementation strategies and frameworks were employed to optimise translation of research findings to improve care.MethodsPatient/stakeholder suggestions were incorporated in a transparent Table of Changes and prioritised using the Person‐Based Approach throughout planning and codesign of Lynch ChoicesTM. An interactive stakeholder meeting was convened to identify barriers and facilitators to clinical implementation of the PtDA.ResultsPatient and stakeholder partnerships drove the direction of the research throughout codesign, resulting in several iterative refinements to the PtDA prior to roll out including the addition of illustrations/videos, clearer presentation of cancer risks and increased accessibility for lower literacy. Barriers and facilitators identified from stakeholders were used to create an implementation process map.ConclusionsCreating an effective, engaging PtDA is not enough. Systematic uptake in real world clinical practice, with its resource limitations, is needed to optimise benefit to patients and clinicians. Assessment of speed and breadth of dissemination and usage will be collected to further evidence the benefit of embedding implementation science methods from the outset to translate research findings into clinical practice.
Transmembrane conformation of the envelope protein of an alpha coronavirus, NL63
Authors: Sučec Iva , Pankratova Yanina , Parasar Mriganka , Hong Mei 
Published: March 2024

AbstractThe envelope (E) proteins of coronaviruses (CoVs) form cation‐conducting channels that are associated with the pathogenicity of these viruses. To date, high‐resolution structural information about these viroporins is limited to the SARS‐CoV E protein. To broaden our structural knowledge of other members of this family of viroporins, we now investigate the conformation of the E protein of the human coronavirus (hCoV), NL63. Using two‐ and three‐dimensional magic‐angle‐spinning NMR, we have measured 13C and 15N chemical shifts of the transmembrane domain of E (ETM), which yielded backbone (ϕ, ψ) torsion angles. We further measured the water accessibility of NL63 ETM at neutral pH versus acidic pH in the presence of Ca2+ ions. These data show that NL63 ETM adopts a regular α‐helical conformation that is unaffected by pH and the N‐terminal ectodomain. Interestingly, the water accessibility of NL63 ETM increases only modestly at acidic pH in the presence of Ca2+ compared to neutral pH, in contrast to SARS ETM, which becomes much more hydrated at acidic pH. This difference suggests a structural basis for the weaker channel conductance of α‐CoV compared to β‐CoV E proteins. The weaker E channel activity may in turn contribute to the reduced virulence of hCoV‐NL63 compared to SARS‐CoV viruses.
Molecular basis for differential recognition of an allosteric inhibitor by receptor tyrosine kinases
Authors: Verma Jyoti , Vashisth Harish 
Published: March 2024

AbstractUnderstanding kinase‐inhibitor selectivity continues to be a major objective in kinase drug discovery. We probe the molecular basis of selectivity of an allosteric inhibitor (MSC1609119A‐1) of the insulin‐like growth factor‐I receptor kinase (IGF1RK), which has been shown to be ineffective for the homologous insulin receptor kinase (IRK). Specifically, we investigated the structural and energetic basis of the allosteric binding of this inhibitor to each kinase by combining molecular modeling, molecular dynamics (MD) simulations, and thermodynamic calculations. We predict the inhibitor conformation in the binding pocket of IRK and highlight that the charged residues in the histidine‐arginine‐aspartic acid (HRD) and aspartic acid‐phenylalanine‐glycine (DFG) motifs and the nonpolar residues in the binding pocket govern inhibitor interactions in the allosteric pocket of each kinase. We suggest that the conformational changes in the IGF1RK residues M1054 and M1079, movement of the ⍺C‐helix, and the conformational stabilization of the DFG motif favor the selectivity of the inhibitor toward IGF1RK. Our thermodynamic calculations reveal that the observed selectivity can be rationalized through differences observed in the electrostatic interaction energy of the inhibitor in each inhibitor/kinase complex and the hydrogen bonding interactions of the inhibitor with the residue V1063 in IGF1RK that are not attained with the corresponding residue V1060 in IRK. Overall, our study provides a rationale for the molecular basis of recognition of this allosteric inhibitor by IGF1RK and IRK, which is potentially useful in developing novel inhibitors with improved affinity and selectivity.
Profiling of urinary steroids aided by lithium ion adduction‐based ultrahigh‐performance liquid chromatography–tandem mass spectrometry
Authors: Pan Yue , Wang Qiuyi , Chen Mengyao , Takao Toshifumi 
Published: March 2024

RationaleAs 3‐OH‐containing steroids are prone to dehydration by conventional electrospray ionization, reducing detection sensitivity, Li ion adduction‐based ultrahigh‐performance liquid chromatography–tandem mass spectrometry (UHPLC/MS/MS), developed to prevent dehydration and effectively detect 3‐OH steroids, was applied for profiling total and free steroids in urine.MethodsFree urinary steroids were isolated directly from urine by solid‐phase extraction (SPE) with 80% acetonitrile. The total steroids were prepared by enzymatic treatment of urine with a cocktail of sulfatase and glucronidase, protein precipitation, and separation with the above SPE. In order to detect as many steroid types as possible, UHPLC/MS/MS (Li method) with Li+ solution added after the column was used for analysis in addition to the conventional method of detecting protonated ions (H method). The 13 3‐OH steroids and the remaining 16 steroids were quantified by standard curves prepared using product ion transitions derived from [M + Li]+ and MH+, respectively.ResultsTwo groups of human urine, male and female urine, were analyzed. 3‐OH steroids could be detected with greater sensitivity using the Li method than the conventional method. The absolute amounts of each steroid were normalized based on creatinine levels. The difference between the male and female groups are clearly attributable to sex steroids.ConclusionsTwenty‐nine total steroids and 19 free steroids were identified in a limited volume (240 mL) of urine. Of these, 13 3‐OH steroids were better detected by Li+ adduction‐based UHPLC/MS/MS.
Synthesis, Characterization, In‐Vitro and In‐Vivo Anti‐Cancer Evaluation of Novel Benzopyrylium Salts on Colorectal Cancer Model of Drosophila Melanogaster
Authors: Rai Prashant , Kumar Rohit , Singh Jyotsna , Saripella Srikrishna , Golakoti Nageswara Rao 
Published: March 2024

AbstractA total of 10 benzopyrylium salts, 7 being novel, were synthesized by Claisen‐Schmidt condensation reaction and characterized by 1H and 13C NMR, High‐Resolution Mass Spectrometry, FT‐IR, and UV‐Vis spectroscopy. The purity of these synthesized compounds was determined by HPLC. The in‐vitro anti‐cancer evaluation of these synthesized benzopyrylium salts was done at National Cancer Institute (NCI), USA, against 60 human cancer cell lines. The compounds 4 and 8 showed promising anti‐cancer activities against various human cancer cell lines. The docking studies of the compounds were carried out against the oncogenic target JNK and their docking scores were compared to that of the known JNK inhibitor SP600125 (Pyrazolanthrone). Compound 4 exhibited an outstanding docking score of −9.0 kcal/mol, comparable to the docking score of SP600125 (−9.3 kcal/mol). The ex‐vivo studies in the hind‐gut of Drosophila were carried out and the inhibitory activity of compound 4 supported the findings of the docking studies. Furthermore, the potent compounds 4 and 8 were taken up for their in‐vivo anti‐cancer evaluation in the colorectal cancer model (CRC) of Drosophila melanogaster. The toxicity studies of these potent compounds were carried out both in wild type and mutant type Drosophila and the lethal doses were determined to be 200 μM.
Room Temperature Catalysts for High Effective Degradation of Formaldehyde: Research Progresses and Challenges
Authors: Chai Liming , Zhai Wenjie , Liu Xuan , Xing Gang , Zhang Bo , Zang Jiaqi , Yang Yifan , Ma Kai , Zhang Jianbin 
Published: March 2024

AbstractFormaldehyde (HCHO) is one of major pollutants in indoor air, and prolonged exposure to HCHO may result in great harm to human health. Therefore, it is crucial to remove HCHO from indoor air at room temperature. In recent years, various room temperature catalysts, which have the advantages of environmental friendliness and energy saving, were developed for high effective catalytic oxidation of HCHO. In this work, research progress and challenges on the room temperature catalytic oxidation of HCHO by using noble metal catalysts and non‐noble metal catalysts are systemically reviewed. Meanwhile, the room temperature catalytic oxidation performance, degradation conditions of HCHO, and room temperature catalytic oxidation mechanism of catalysts was also discussed.
Design and Synthesis of Novel 6,7‐Dihydrobenzo[d]isoxazol‐4(5H)‐one Derivatives Bearing 1,2,3‐Triazole Moiety as Potential Hsp90 Inhibitors and their Evaluation as Antiproliferative Agents
Authors: Varabyeva Nastassia A. , Salnikova Diana I. , Krymov Stepan K. , Bogdanov Fedor B. , Shchekotikhin Andrey E. , Puzanau Raman M. , Sorokin Danila V. , Lakhvich Fedor A. , Scherbakov Alexander M. , Piven Yuri A. 
Published: March 2024

AbstractAn effective approach to 5‐triazolyl‐substituted 6,7‐dihydrobenzo[d]isoxazol‐4(5H)‐ones and 4,5,6,7‐tetrahydrobenzo[d]isoxazoles was developed. The approach included α‐keto bromination of 6,7‐dihydrobenzo[d]isoxazol‐4(5H)‐one followed by nucleophilic substitution of bromine with the azide group. For the preparation of 5‐azido‐6,7‐dihydrobenzo[d]isoxazol‐4(5H)‐one, the carbonyl group at position 4 was reduced to a methylene group under ionic hydrogenation conditions using triethylsilane as a reducing agent. Cu(I)‐catalyzed [2+3] cycloaddition of terminal alkynes to both obtained azides was used for the synthesis of two series of triazolyl derivatives. Compounds, which contain in their structures common for some Hsp90 inhibitors 2,4‐dihydroxy‐5‐isopropylphenyl fragment, were evaluated as antiproliferative agents against two breast cancer cell lines: hormone‐dependent MCF7 and HER2‐positive HCC1954. The lead compound showed half‐maximal inhibitory concentration (IC50) values below 5 μM and induced significant changes in the Hsp90 signaling pathways in HER2‐positive HCC1954 cells. It increased the expression of Hsp70 (used as a pharmacodynamic marker of Hsp90 inhibition) and inhibited the expression of HER2, p‐c‐Met, c‐Met, and p‐AKT. The combination of the selected isoxazole‐triazole hybrid molecule and the earlier described apoptosis inducer LCTA‐3344 demonstrated a significant antiproliferative effect against HCC1954 cells. The lead compound was revealed to be a promising candidate for future anticancer drug design, particularly against aggressive breast cancer positive for HER2.
Effect of CTAB premicelle and micelle formation on Bromophenol Blue spectra
Authors: Zheng Junyu , Ma Zongbin , Zhang Qi , Qiu Lu , Wang Zhihang , Wang Nong 
Published: March 2024

AbstractThe interactions between surfactants and dyes in aqueous solutions are essential for gaining insights into dyeing processes across various industries and for driving advancements in chemical research. This paper investigates the interaction between the anionic dye bromophenol blue (BPB) and the cationic surfactant cetyltrimethylammonium bromide (CTAB) in aqueous solutions. It was observed that the absorbance value at the maximum absorption peak of BPB changes systematically with increasing CTAB concentration, revealing the critical premicelle concentration (cpc) and critical micelle concentration (cmc) of CTAB. Employing a micellization model and measuring the electric conductivity across different concentrations of CTAB, the micellization thermodynamic parameters of CTAB, both in the absence and presence of BPB, were determined. The findings indicate that the associative interaction between BPB and CTAB significantly influences the formation of CTAB micelles.
Synthesis of Novel MOF‐Based BixTiy‐BTC and Bi1Ti3‐BTC/Fe3O4 Photocatalysts and Their Application in the Degradation of UDMH in Wastewater
Authors: Zhou Feng , Xie Chen , Huo Yonggang , Yao Qingxu 
Published: March 2024

AbstractRemoval of organic pollutants from wastewater remains a significant challenge. Hence, we report a series of novel MOFs based BixTiy‐BTC photocatalysts synthesized by hydrothermal method for decontamination of 1,1‐Dimethylhydrazine (UDMH). The preparation parameters of MOFs were optimized, the best catalytic performance was achieved by adjusting the Bi/Ti molar ratio to 1 : 3, with Bi1Ti3‐BTC a photocurrent density of 0.35 mA/cm2 was reached. The morphology and composition of the materials were analyzed, titanium doping increased the specific surface area. Bi1Ti3‐BTC was loaded with magnetic nano‐Fe3O4, which prevented agglomeration of Bi1Ti3‐BTC and increased the specific surface area, thus improving photocatalytic activity. The band gap structure of the semiconductor materials was estimated by UV‐Vis and XPS valence band spectra, while the separation efficiency of photogenerated carriers was investigated by photocurrent density and PL (Photoluminescence) spectrum. The photocatalytic degradation rate of UDMH rapidly decreased after addition of EDTA, indicating that h+ was the main active species in the photocatalytic degradation process. The photocatalytic removal efficiency of UDMH with Bi1Ti3‐BTC/Fe3O4 at a concentration of 0.5 g/L reached 97.58 % after illumination for 180 min, and after 210 min near quantitative degradation was observed.
Multifunctional Gold Nanozyme‐Engineered Amphotericin B for Enhanced Antifungal Infection Therapy
Authors: Jiang Chunmei , Li Fangping , Song Pei , Wen Mengyao , Yang Saixue , Tian Geng , Shao Dongyan , Shi Junling , Shang Li 
Published: March 2024

AbstractChronic wounds of significant severity and acute injuries are highly vulnerable to fungal infections, drastically impeding the expected wound healing trajectory. The clinical use of antifungal therapeutic drug is hampered by poor solubility, high toxicity and adverse reactions, thereby necessitating the urgent development of novel antifungal therapy strategy. Herein, this study proposes a new strategy to enhance the bioactivity of small‐molecule antifungal drugs based on multifunctional metal nanozyme engineering, using amphotericin B (AmB) as an example. AmB‐decorated gold nanoparticles (AmB@AuNPs) are synthesized by a facile one‐pot reaction strategy, and the AmB@AuNPs exhibit superior peroxidase (POD)‐like enzyme activity, with maximal reaction rates (Vmax) 3.4 times higher than that of AuNPs for the catalytic reaction of H2O2. Importantly, the enzyme‐like activity of AuNPs significantly enhanced the antifungal properties of AmB, and the minimum inhibitory concentrations of AmB@AuNPs against Candida albicans (C. albicans) and Saccharomyces cerevisiae (S. cerevisiae) W303 are reduced by 1.6‐fold and 50‐fold, respectively, as compared with AmB alone. Concurrent in vivo studies conducted on fungal‐infected wounds in mice underscored the fundamentally superior antifungal ability and biosafety of AmB@AuNPs. The proposed strategy of engineering antifungal drugs with nanozymes has great potential for enhanced therapy of fungal infections and related diseases.
Electronic Properties of CrB/Co2CO2 Superlattices by Multiple Descriptor‐Based Machine Learning Combined with First‐Principles
Authors: Yuan Yuanyuan , Ren Junqiang , Xue Hongtao , Li Junchen , Tang Fuling , Guo Xin , Lu Xuefeng 
Published: March 2024

AbstractIn recent times, newly unveiled 2D materials exhibiting exceptional characteristics, such as MBenes and MXenes, have gained widespread application across diverse domains, encompassing electronic devices, catalysis, energy storage, sensors, and various others. Nonetheless, numerous technical bottlenecks persist in the development of high‐performance, structurally flexible, and adjustable electronic device materials. Research investigations have demonstrated that 2D van der Waals superlattices (vdW SLs) structures comprising materials exhibit exceptional electrical, mechanical, and optical properties. In this work, the advantages of both materials are combined and compose the vdW SLs structure of MBenes and MXenes, thus obtaining materials with excellent electronic properties. Furthermore, it integrates machine learning (ML) with first‐principles methods to forecast the electrical properties of MBene/MXene superlattice materials. Initially, various configurations of MBene/MXene superlattice materials are explored, revealing that distinct stacking methods exert significant influence on the electronic structure of MBene/MXene materials. Specifically, the BABA‐type stacking of CrB (layer A) and Co2CO2 MXene (layer B) is most stable configureation. Subsequently, multiple descriptors of the structure are constructed to predict the density of states of vdW SLs through the employment of ML techniques. The best model achieves a mean absolute error (MAE) as low as 0.147 eV.
Flexural stiffness of RC beams with high‐strength steel bars after exposure to elevated temperatures
Authors: Zhao Jun , Jiang Yibo , Cai Gaochuang , Deng Xiangsheng , Si Larbi Amir 
Published: March 2024

AbstractIn this paper, the flexural stiffness of the reinforced concrete (RC) beams reinforced with high‐strength steel bars after exposure to different elevated temperatures was investigated experimentally and theoretically. The effects of the elevated temperature (room temperature, 200°C, 400°C, 600°C, 800°C, and 1000°C), high‐temperature duration time (0 h, 1 h, and 2 h), and steel bar types (HRB600 and HRB500) on the load–deflection response, load–stiffness response, and crack distribution of tested beams were investigated. The results showed that when the temperature is below 600°C, the effect of high temperature on the stiffness reduction of high‐strength RC beams is not significant, while the beams reduced the stiffness when the exposure temperature reached 800°C and 1000°C, regardless of the type of the steel bars. The elevated temperature accelerated the development of the deflection of RC beams, and the bending stiffness of the RC beams decreased more severely as the increase of duration time. By using appropriate degradation factors, the residual stiffness of the beams was predicted well by the analysis calculation method and the effective inertia moment calculation method, for example, the prediction accuracy is over 91% and 85.8% for the cases under and over 800°C, respectively. However, for the beams at 1000°C, a correction coefficient (0.652) was applied to improve the accuracy of the calculative stiffness of the HRB600 RC beams at the service load stage.
Artificial Intelligence-Based Counting Algorithm Enables Accurate and Detailed Analysis of the Broad Spectrum of Spot Morphologies Observed in Antigen-Specific B-Cell ELISPOT and FluoroSpot Assays
Authors: Karulin Alexey Y. , Katona Melinda , Megyesi Zoltán , Kirchenbaum Greg A. , Lehmann Paul V. 
Published: March 2024

AbstractAntigen-specific B-cell ELISPOT and multicolor FluoroSpot assays, in which the membrane-bound antigen itself serves as the capture reagent for the antibodies that B cells secrete, inherently result in a broad range of spot sizes and intensities. The diversity of secretory footprint morphologies reflects the polyclonal nature of the antigen-specific B cell repertoire, with individual antibody-secreting B cells in the test sample differing in their affinity for the antigen, fine epitope specificity, and activation/secretion kinetics. To account for these heterogeneous spot morphologies, and to eliminate the need for setting up subjective counting parameters well-by-well, CTL introduces here its cutting-edge deep learning-based IntelliCount™ algorithm within the ImmunoSpot® Studio Software Suite, which integrates CTL’s proprietary deep neural network. Here, we report detailed analyses of spots with a broad range of morphologies that were challenging to analyze using standard parameter-based counting approaches. IntelliCount™, especially in conjunction with high dynamic range (HDR) imaging, permits the extraction of accurate, high-content information of such spots, as required for assessing the affinity distribution of an antigen-specific memory B-cell repertoire ex vivo. IntelliCount™ also extends the range in which the number of antibody-secreting B cells plated and spots detected follow a linear function; that is, in which the frequencies of antigen-specific B cells can be accurately established. Introducing high-content analysis of secretory footprints in B-cell ELISPOT/FluoroSpot assays, therefore, fundamentally enhances the depth in which an antigen-specific B-cell repertoire can be studied using freshly isolated or cryopreserved primary cell material, such as peripheral blood mononuclear cells.