bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Clinical Anatomy Fellowship: Revolutionizing curricular experiences for faculty and students
Authors: Murtha Celeste M. , Thiel Grace E. , Dennis Jennifer F. , Hopper Mari 
Published: February 2024

AbstractFellows completing the Clinical Anatomy Fellowship at Kansas City University assist Anatomy faculty in the Gross Anatomy laboratory, complete robust research projects, and support other departments. The program's positive impact on participants has been reported; however, the impact on individuals interfacing with Fellows has not been investigated. A follow‐up, survey‐based (Likert scale, multiple‐choice, open‐ended) study was conducted to evaluate faculty, staff, and student perceptions of the program. Ninety‐five percent of surveyed faculty and staff (n = 22) perceived the Fellows as beneficial to students, faculty, and the university (p < 0.05) by acting as role models (95%) and mentors (90%), contributing to educational processes (90%), and reducing faculty work burden (81%) (p < 0.05). Student responses (n = 95) were also positive: 97% perceived interactions with Fellows as beneficial (p < 0.05). A passion for Anatomy (mean, 4.6; p < 0.05) and the opportunity to increase competitiveness for residency (mean, 4.5; p < 0.05) were the most important factors driving interest in the Fellowship (Cronbach's alpha, 0.766). In contrast, diverting a year from the school's curriculum (mean, 4.4; p < 0.05) and delaying clinical experiences (mean, 4.3; p < 0.05) were the most important deterrents (Cronbach's alpha, 0.505). Additionally, the financial investment required by the program is lower than that associated with hiring full‐time faculty. Analysis comparing employment of Fellows versus associate‐level faculty identified annual net savings of $370,000. Not only does the Fellowship augment faculty and student experiences at the university, but it also allows for substantial cost savings. Collectively, these data are evidence for other health professional institutions to consider adopting a similar program.
Production and characterization of cellulose acetate using olive tree pruning biomass as feedstock
Authors: Rodríguez‐Liébana José Antonio , Robles‐Solano Esther , Jurado‐Contreras Sofia , Morillas‐Gutiérrez Francisca , Moya Alberto J. , Mateo Soledad , Navas‐Martos Francisco Javier , La Rubia M. Dolores 
Published: February 2024

AbstractOlive tree pruning (OTP) is one of the most abundant sources of biomass waste in the Mediterranean basin. This is especially relevant in southern Spain where olive oil production represents a large part of the economy. Olive tree prunings are mostly either burned or are spread in olive orchards as an organic amendment, or used for heat generation on a domestic scale. However, the lignocellulosic composition of OTP makes it a potential source of biopolymers, thus providing an excellent economic alternative for the olive oil sector. In this work, pretreated OTP fibers were subjected to an optimized alkaline treatment followed by a single‐step bleaching reaction with H2O2. Afterwards, the cellulose pulp was transformed chemically to obtain cellulose acetate. Noncellulosic components were removed effectively from OTP, thus obtaining a pulp highly purified in cellulose with 71% crystallinity and 355 °C maximum degradation temperature. Nevertheless, a very large amount of cellulose (ca. 50%) was eliminated throughout the process, especially during acid pretreatment, which was responsible for 38% solubilization. A similar level of acetylation and degree of substitution was obtained by using acetylation times in the range of 1 to 6 h. No large differences were observed in the infrared spectra and X‐ray diffractograms of the synthesized acetates. However, their thermal stability varied significantly with reaction time, evolving from a multistep degradation pattern to a single and sharp peak between 300 and 400 °C with increasing time. Thermogravimetric curves revealed that at least 5 h (preferably 6 h) were needed to obtain cellulose acetate from OTP with adequate thermal stability for further processing.
An optimized polymeric delivery system for piggyBac transposition
Authors: Meenakshi Sundaram Daniel Nisakar , Bahadur K. C. Remant , Fu Wei , Uludağ Hasan 
Published: February 2024

AbstractThe piggyBac transposon/transposase system has been explored for long‐term, stable gene expression to execute genomic integration of therapeutic genes, thus emerging as a strong alternative to viral transduction. Most studies with piggyBac transposition have employed physical methods for successful delivery of the necessary components of the piggyBac system into the cells. Very few studies have explored polymeric gene delivery systems. In this short communication, we report an effective delivery system based on low molecular polyethylenimine polymer with lipid substitution (PEI‐L) capable of delivering three components, (i) a piggyBac transposon plasmid DNA carrying a gene encoding green fluorescence protein (PB‐GFP), (ii) a piggyBac transposase plasmid DNA or mRNA, and (iii) a 2 kDa polyacrylic acid as additive for transfection enhancement, all in a single complex. We demonstrate an optimized formulation for stable GFP expression in two model cell lines, MDA‐MB‐231 and SUM149 recorded till day 108 (3.5 months) and day 43 (1.4 months), respectively, following a single treatment with very low cell number as starting material. Moreover, the stability of the transgene (GFP) expression mediated by piggyBac/PEI‐L transposition was retained following three consecutive cryopreservation cycles. The success of this study highlights the feasibility and potential of employing a polymeric delivery system to obtain piggyBac‐based stable expression of therapeutic genes.
Supervised and unsupervised machine learning approaches for monitoring subvisible particles within an aluminum‐salt adjuvanted vaccine formulation
Authors: Greenblott David N. , Wood Caitlin V. , Zhang Jingtao , Viza Nelia , Chintala Ramesh , Calderon Christopher P. , Randolph Theodore W. 
Published: February 2024

AbstractSuspensions of protein antigens adsorbed to aluminum‐salt adjuvants are used in many vaccines and require mixing during vial filling operations to prevent sedimentation. However, the mixing of vaccine formulations may generate undesirable particles that are difficult to detect against the background of suspended adjuvant particles. We simulated the mixing of a suspension containing a protein antigen adsorbed to an aluminum‐salt adjuvant using a recirculating peristaltic pump and used flow imaging microscopy to record images of particles within the pumped suspensions. Supervised convolutional neural networks (CNNs) were used to analyze the images and create “fingerprints” of particle morphology distributions, allowing detection of new particles generated during pumping. These results were compared to those obtained from an unsupervised machine learning algorithm relying on variational autoencoders (VAEs) that were also used to detect new particles generated during pumping. Analyses of images conducted by applying both supervised CNNs and VAEs found that rates of generation of new particles were higher in aluminum‐salt adjuvant suspensions containing protein antigen than placebo suspensions containing only adjuvant. Finally, front‐face fluorescence measurements of the vaccine suspensions indicated changes in solvent exposure of tryptophan residues in the protein that occurred concomitantly with new particle generation during pumping.
Contributions of Chinese hamster ovary cell derived extracellular vesicles and other cellular materials to hollow fiber filter fouling during perfusion manufacturing of monoclonal antibodies
Authors: Zhang Yixiao , Madabhushi Sri , Tang Tiffany , Raza Hassan , Busch David J. , Zhao Xi , Ormes James , Xu Sen , Moroney Joseph , Jiang Rubin , Lin Henry , Liu Ren 
Published: February 2024

AbstractHollow fiber filter fouling is a common issue plaguing perfusion production process for biologics therapeutics, but the nature of filter foulant has been elusive. Here we studied cell culture materials especially Chinese hamster ovary (CHO) cell‐derived extracellular vesicles in perfusion process to determine their role in filter fouling. We found that the decrease of CHO‐derived small extracellular vesicles (sEVs) with 50–200 nm in diameter in perfusion permeates always preceded the increase in transmembrane pressure (TMP) and subsequent decrease in product sieving, suggesting that sEVs might have been retained inside filters and contributed to filter fouling. Using scanning electron microscopy and helium ion microscopy, we found sEV‐like structures in pores and on foulant patches of hollow fiber tangential flow filtration filter (HF‐TFF) membranes. We also observed that the Day 28 TMP of perfusion culture correlated positively with the percentage of foulant patch areas. In addition, energy dispersive X‐ray spectroscopy‐based elemental mapping microscopy and spectroscopy analysis suggests that foulant patches had enriched cellular materials but not antifoam. Fluorescent staining results further indicate that these cellular materials could be DNA, proteins, and even adherent CHO cells. Lastly, in a small‐scale HF‐TFF model, addition of CHO‐specific sEVs in CHO culture simulated filter fouling behaviors in a concentration‐dependent manner. Based on these results, we proposed a mechanism of HF‐TFF fouling, in which filter pore constriction by CHO sEVs is followed by cake formation of cellular materials on filter membrane.
Gender diversity, foreign direct investment spillovers, and productivity: Unraveling the role of female workers in Indonesia
Authors: Yasin Mohammad Zeqi , Harianto Samuel Kharis , Teguh Sambodo Leonardo A. A. , Yustiningsih Firdaussy , Esquivias Miguel Angel 
Published: February 2024

AbstractThis study investigates the impact of gender diversity on firm productivity following foreign direct investment (FDI) spillover. Using Indonesian firm‐level datasets from 2011 to 2015, we employ gender spillovers to assess women's distinct contributions to labor spillovers, often manifested through their impacts on productivity, knowledge sharing, and innovation. A fixed‐effects estimator using Driscoll and Kraay's standard errors was employed to deal with cross‐sectional dependence. We first examined the intra‐industry spillover effects of FDI, followed by spatial spillovers, to evaluate the influence of one province's productivity changes on neighboring provinces. Our findings reveal significant gender‐driven FDI spillovers in the spatial dimension but not within the sector. The consistent results across subsamples (impacts on domestic firms, Java‐non‐Java Island, feminization degree, and industrial technology intensity) align with theoretical studies that emphasize the influence of geographical proximity on FDI spillovers. No significant intra‐industry spillover effects were observed. Further exploration of informal channels, possibly mediating spillover effectiveness, is recommended to provide insights into the observed sectoral dynamics.
The spectrum of concern for medical child abuse among adolescents with chronic pain due to central sensitisation
Authors: Johnson Katie L. , Tham See Wan , Brown Emily C. B. , Walco Gary A. , Feldman Kenneth W. , Wiester Rebecca T. , Wilkins Stephanie N. , Campbell Kristine A. 
Published: February 2024

AbstractAdolescents with chronic pain can at times present with disability out of proportion to diagnostic workup. This is also a defining feature of medical child abuse (MCA). The aim of this study was to identify themes from the clinical narratives of adolescents with chronic pain that may indicate concern for MCA. This qualitative, retrospective study at an academic children's hospital between 2011 and 2019 identified 37 adolescents aged 13–18 years old with chronic pain and varying levels of concern for MCA. Conventional, inductive content analysis was used to identify themes from the medical records of all patients, which were reviewed by an interdisciplinary panel of experts. Themes were organised into three tiers related to the level of concern for MCA: ‘Green zone’ themes including fatigue or sleep problems, psychosocial distress, and social withdrawal were common among all patients. ‘Yellow zone’ themes including fragmented care, caregiver catastrophising, caregiver misrepresentation, medical provider exasperation, and sick identity were more common among patients in whom medical providers raised concern for MCA. A single ‘red zone’ theme, reportable harm to the child, was only present in patients diagnosed by a child abuse paediatrician as having MCA. A visual display of the results is provided for further research and clinical application.
Synthesis and Evaluation of New Phytotoxic Fluorinated Chalcones as Photosystem II and Seedling Growth Inhibitors
Authors: de Pádua Geilly Mara Silva , Pitteri Taciane Santos , Ferreira Basso Marcelo Augusto , de Vasconcelos Leonardo Gomes , Ali Akbar , Dall'Oglio Evandro Luiz , Sampaio Olívia Moreira , Curcino Vieira Lucas Campos 
Published: February 2024

AbstractThe development of novel phytotoxic compounds has been an important aim of weed control research. In this study, we synthesized fluorinated chalcone derivatives featuring both electron‐donating and electron‐withdrawing groups. These compounds were evaluated both as inhibitors of the photosystem II (PSII) electron chain as well as inhibitors of the germination and seedling growth of Amaranthus plants. Chlorophyll a (Chl a) fluorescence assay was employed to evaluate their effects on PSII, while germination experiments were conducted to assess their impact on germination and seedling development. The results revealed promising herbicidal activity for (E)‐3‐(4‐bromophenyl)‐1‐(4‐fluorophenyl)prop‐2‐en‐1‐one (7 a) and (E)‐1‐(4‐fluorophenyl)‐3‐phenylprop‐2‐en‐1‐one (7 e). Compounds 7 a and 7 e exhibited a reduction in Chl a parameters associated with performance indexes and electron transport per reaction center. This reduction suggests a decrease in PSII activity, attributed to the blockage of electron flow at the quinone pool. Molecular docking analyses of chalcone derivatives with the D1 protein of PSII revealed a stable binding conformation, wherein the carbonyl and fluorine groups interacted with Phe265 and His215 residues, respectively. Additionally, at a concentration of 100 μM, compound 7 e demonstrated pre‐ and post‐emergent herbicidal activity, resulting in a reduction of the seed germination index, radicle and hypocotyl lengths of Amaranthus weeds.
Exploring the Therapeutic Potential of Lawsone and Nanoparticles in Cancer and Infectious Disease Management
Authors: Kamil Zaidan Haider , Jasim Al‐Khafaji Hanadi Had , Al‐dolaimy F. , Abed Hussein Shaymaa , Otbah Farqad Rand , Thabit Daha , Talib Kareem Ashwaq , Ramadan Montather F. , Hamood Sarah A. , Alawadi Ahmed Hussien , Alsaalamy Ali 
Published: February 2024

AbstractLawsone, a naturally occurring compound found in henna, has been used in traditional medicine for centuries due to its diverse biological activities. In recent years, its nanoparticle‐based structure has gained attention in cancer and infectious disease research. This review explores the therapeutic potential of lawsone and its nanoparticles in the context of cancer and infectious diseases. Lawsone exhibits promising anticancer properties by inducing apoptosis and inhibiting cell proliferation, while its nanoparticle formulations enhance targeted delivery and efficacy. Moreover, lawsone demonstrates significant antimicrobial effects against various pathogens. The unique physicochemical properties of lawsone nanoparticles enable efficient cellular uptake and targeted delivery. Potential applications in combination therapy and personalized medicine open new avenues for cancer and infectious disease treatment. While clinical trials are needed to validate their safety and efficacy, lawsone‐based nanoparticles offer hope in addressing unmet medical needs and revolutionizing therapeutic approaches.
Tris‐Functionalized Polyoxotungstovanadate‐Mediated Antitumor Efficacy Involves Multiple Cell Death Pathways
Authors: Chen Lihong , Zhao Zijia , Diarimalala Rominah Onintsoa , Chen Zhongwei , Wang Yu , Zhan Taozhu , Zhao Yanchao , Ma Chunhui , Wang Xingyue , Zhao Chenqi , Xiao Zicheng , Hu Kanghong , Wu Pingfan 
Published: February 2024

AbstractPolyoxometalates (POMs) are promising inorganic drug candidates for cancer chemotherapy. They are becoming attractive because of their easy accessibility and low cost. Herein, we report the synthesis and antitumor activity studies of four Lindqvist‐type POMs with mixed‐addenda atoms Na2[V4W2O16{(OCH2)3CR}] (R=−CH2OH, −CH3, −CH2CH3) and (Bu4N)2[V3W3{(OCH2)3CH2OOCCH2CH3}]. Compared with the current clinical applied antitumor drug 5‐fluorouracil (5‐FU) or Gemcitabine, analysis of MTT/CCK‐8 assay, colony formation and wound healing assay revealed that the {V4W2} POMs had acceptable cytotoxicity in normal cells (293T) and significant inhibitory effects on cell proliferation and migration in three human tumor cell lines: human lung carcinoma cells (A549), human cervical carcinoma cells (HeLa), and human breast cancer cells (MCF‐7). Interestingly, among the POMs analyzed, the therapeutic index (TI) of the {V4W2} POM with R= ‐CH2OH was relatively the most satisfactory. Thus, it was subsequently used for further studies. Flow cytometry analysis showed it prompted cellular apoptosis rate. qRT‐PCR and Western blotting analysis indicated that multiple cell death pathways were activated including apoptosis, autophagy, necroptosis and pyroptosis during the POM‐mediated antitumor process. In conclusion, our study shows that the polyoxotungstovanadate has great potential to be developed into a broad‐spectrum antitumor chemotherapeutic drug.
Discovery of a Photoaffinity Probe that Captures the Active Conformation of the Cannabinoid CB2 Receptor
Authors: De Paus Laura V. , An Yu , Janssen Antonius P. A. , van den Berg Richard J. B. H. N. , Heitman Laura H. , van der Stelt Mario 
Published: February 2024

AbstractThe cannabinoid receptor type 2 (CB2R) is a G protein‐coupled receptor with therapeutic potential for the treatment of inflammatory disorders. Fluorescent probes are desirable to study its receptor localization, expression and occupancy. Previously, we have reported a photoaffinity probe LEI‐121 that stabilized the inactive conformation of the CB2R. Here, we report the structure‐based design of a novel bifunctional probe that captures the active conformation of the CB2R upon irradiation with light. An alkyne handle was incorporated to visualize the receptor using click‐chemistry with fluorophore‐azides. These probes may hold promise to study different receptor conformations in relation to their cellular localization and function.
Chemodivergent Dehydrogenative Coupling of Alcohols by 3d Metal Catalysts
Authors: Bansal Sadhna , Punji Benudhar 
Published: February 2024

AbstractChemodivergent synthesis by transition metal catalysts is a straightforward and sustainable approach to achieving valuable organic compounds. Especially, the chemodivergent dehydrogenative couplings of alcohols with organic motifs to develop various saturated and unsaturated compounds are highly environmentally benign due to the reduced waste generation. In this concept review, we presented the 3d transition metal (Mn, Fe, Co, and Ni)‐catalyzed chemodivergent synthesis of imines and amines, saturated and unsaturated carbonyl/alcohol compounds, saturated and unsaturated nitriles, N‐heterocycles, and N‐/C‐alkylated indoles. The discussed reaction commanded two or three different products with high chemoselectivity by changing specific reaction parameters, but keeping the catalyst unchanged. Generally, the acceptorless dehydrogenative coupling (ADC) provides unsaturated moieties, whereas the borrowing‐hydrogen (BH) process results in saturated compounds.
Acrylate‐derived RAFT Polymers for Enzyme Hyperactivation – Boosting the α‐Chymotrypsin Enzyme Activity Using Tailor‐Made Poly(2‐Carboxyethyl)acrylate (PCEA)
Authors: Müllers Yannic , Sadr Ahmad Shahir , Schenderlein Matthias , Pallab Nazim , Davari Mehdi D. , Glebe Ulrich , Reifarth Martin 
Published: February 2024

AbstractWe study the hyperactivation of α‐chymotrypsin (α‐ChT) using the acrylate polymer poly(2‐carboxyethyl) acrylate (PCEA) in comparison to the commonly used poly(acrylic acid) (PAA). The polymers are added during the enzymatic cleavage reaction of the substrate N‐glycyl‐L‐phenylalanine p‐nitroanilide (GPNA). Enzyme activity assays reveal a pronounced enzyme hyperactivation capacity of PCEA, which reaches up to 950 % activity enhancement, and is significantly enhanced to PAA (revealing an activity enhancement of approx. 450 %). In a combined experimental and computational study, we investigate α‐ChT/polymer interactions to elucidate the hyperactivation mechanism of the enzyme. Isothermal titration calorimetry reveals a pronounced complexation between the polymer and the enzyme. Docking simulations reveal that binding of polymers significantly improves the binding affinity of GPNA to α‐ChT. Notably, a higher binding affinity is found for the α‐ChT/PCEA compared to the α‐ChT/PAA complex. Further molecular dynamics (MD) simulations reveal changes in the size of the active site in the enzyme/polymer complexes, with PCEA inducing a more pronounced alteration compared to PAA, facilitating an easier access for the substrate to the active site of α‐ChT.
QM/MM Study Into the Mechanism of Oxidative C=C Double Bond Cleavage by Lignostilbene‐α,β‐Dioxygenase
Authors: Ali Hafiz Saqib , de Visser Sam P. 
Published: February 2024

AbstractThe enzymatic biosynthesis of fragrance molecules from lignin fragments is an important reaction in biotechnology for the sustainable production of fine chemicals. In this work we investigated the biosynthesis of vanillin from lignostilbene by a nonheme iron dioxygenase using QM/MM and tested several suggested proposals via either an epoxide or dioxetane intermediate. Binding of dioxygen to the active site of the protein results in the formation of an iron(II)−superoxo species with lignostilbene cation radical. The dioxygenase mechanism starts with electrophilic attack of the terminal oxygen atom of the superoxo group on the central C=C bond of lignostilbene, and the second‐coordination sphere effects in the substrate binding pocket guide the reaction towards dioxetane formation. The computed mechanism is rationalized with thermochemical cycles and valence bond schemes that explain the electron transfer processes during the reaction mechanism. Particularly, the polarity of the protein and the local electric field and dipole moments enable a facile electron transfer and an exergonic dioxetane formation pathway.
Comparative Analysis of pH Prediction Routines in ADM1 and a Specialized Water Chemistry Simulator
Authors: Kosse Pascal , Hernández Rodríguez Tanja , Frahm Björn , Lübken Manfred , Wichern Marc 
Published: February 2024

AbstractIn anaerobic technology, pH values are crucial for targeted volatile fatty acid production. While pH dynamics can be modeled using the Anaerobic Digestion Model No. 1 (ADM1), simulation results may be biased. To address this issue, the pH prediction routine of Visual Water, a specialized water chemistry simulator, was validated. Unlike ADM1, it accounts for ionic strength and activities while also providing an automated uncertainty analysis. The analysis revealed Visual Water simulations to better fit measured pH data from acidic solutions in a miniaturized stirred‐tank reactor.