bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA Vaccination against Channel Catfish Virus Results in Minimal Immune Response and is Not Efficacious against Challenge
Authors: Harbottle Heather , Plant Karen P. , Thune Ronald L.
Published: August 2005

We evaluated DNA vaccination against channel catfish virus (CCV) by comparing 11 encoded genes, multiple doses, codelivery of DNA vaccines, and the resultant immune responses, as well as making a direct comparison with previously published DNA vaccines for CCV. The genes selected included immediate early genes, membrane genes, the major capsid gene, and the putative major envelope glycoprotein gene. The open reading frame (ORF) for each gene was amplified by using the polymerase chain reaction, cloned into pcDNA3.1/V5/His-TOPO, and expression of the predicted molecular weight proteins was confirmed in cell culture. Each vaccine was injected intramuscularly in doses of 50, 25, 5, or 1 μg and evaluated by immersion challenge. Detection of mRNA specific for ORF 59 and ORF 6 at the injection site indicated that the DNA vaccines were transcriptionally active in situ. Serum-neutralizing titers, enzyme-linked immunosorbant assay (ELISA) antibody titers, and Mx transcription were measured in response to vaccination. Significant protection was not observed in any experiment, including groups receiving multiple constructs. Published DNA vaccines encoding one of the outer membrane protein genes and the putative major envelope glycoprotein gene also failed to protect against disease in direct comparison with those constructed here, singly or in combination. Serum-neutralizing and ELISA antibody titers were generally low and not significantly different between groups. Mx transcription was induced in response to vaccination with both single and multiple DNA constructs. Although both innate and adaptive immune responses were detected in response to DNA vaccination for CCV, vaccination was not protective for any of the constructs tested.
AI Institute in Dynamic Systems: Developing machine learning and AI tools for scientific discovery, engineering design, and data‐driven control
Authors: Kutz J. Nathan , Brunton Steven L. , Manohar Krithika , Lipson Hod , Li Na
Published: February 2024

The mission of the AI Institute in Dynamic Systems is to develop the next generation of advanced machine learning (ML) and AI tools for controlling complex physical systems by discovering physically interpretable and physics‐constrained data‐driven models through optimal sensor selection and placement. The research effort is anchored by a common task framework (CTF) that evaluates the performance of ML algorithms, architectures, and optimization schemes for the diverse tasks required in engineering applications. The aim is to push beyond the boundaries of modern techniques by closing the loop between data collection, control, and modeling, creating a unique and cross‐disciplinary architecture for learning physically interpretable and physics constrained models of complex dynamic systems from time series data. The CTF further supports sustainable and open‐source challenge datasets, which are foundational for developing interpretable, ethical, and inclusive tools to solve problems fundamental to human safety, society, and the environment.
Flexible Grippers with Programmable Three‐Dimensional Magnetization and Motions
Authors: Fan Shengying , Yang Wenwen , Wei Jiajie , Wang Jing , Wang Xiaolei , Wu Dong , Cheng Wei
Published: February 2024

Programmable magnetic soft grippers are highly desirable for diverse applications in drug delivery, object manipulation, and soft robotics. However, current magnetic programming grippers need to be driven by multiple physical fields, which are complicated to operate and single in motion. Here, a method for patterning hard magnetic microparticles in an elastomer matrix is reported. Based on digital light processing (DLP), this method uses controlled reorientation of magnetic particles and selective exposure to ultraviolet (UV) light to encode magnetic particles in polydimethylsiloxane (PDMS) materials with arbitrary three‐dimensional (3D) orientation. The combination of vertical and horizontal magnetic fields can produce different forces, causing different deformation modes of the grippers. Flexible grippers can be fabricated from a single precursor in one process and produce various deformation and motion forms when a single magnetic field is applied. Moreover, the gripper has the advantages of simple manipulation, fast response, and flexible movement, which is of great significance in the application of biological devices and soft robots.
An Intelligent Redox‐Responsive DNA Circuit for Robust On‐Site Profiling of Glutathione‐MicroRNA Signaling Pathway
Authors: Wang Yifei , Shang Jinhua , He Yuqiu , Zhang Qingqing , Liu Xiaoqing , Wang Fuan
Published: February 2024

Synthetic biochemical circuits (e.g., DNA circuits) remain at the forefront of intracellular biosensing tasks yet are hindered by the undesired off‐site activation and the accompanying signal leakage. Herein, the study attempts to overcome this limitation by developing a simple‐yet‐powerful endogenous glutathione (GSH)‐regulating tactic that permits robust and distinguishable on‐site microRNA (miRNA) imaging under disturbed redox homeostasis. Specifically, a hierarchically activated catalytic DNA (HAD) circuit is fabricated by grafting the disulfide linkage within entropy‐driven DNA circuitry (EDC) reactants. It is exemplified that this HAD system promises the spatiotemporally selective microRNA‐21 (miR‐21) imaging in living cells and the robust differentiation of tumor cells from normal cells. The correlationship between GSH and miRNA is extensively explored in live cells, and can substantially expand the toolbox of DNA circuits for profiling intracellular biochemical processes.
Oral Delivery of the Vancomycin Derivative FU002 by a Surface‐Modified Liposomal Nanocarrier
Authors: Werner Julia , Umstätter Florian , Hertlein Tobias , Mühlberg Eric , Beijer Barbro , Wohlfart Sabrina , Zimmermann Stefan , Haberkorn Uwe , Ohlsen Knut , Fricker Gert , Mier Walter , Uhl Philipp
Published: February 2024

Oral delivery of peptide therapeutics faces multiple challenges due to their instability in the gastrointestinal tract and low permeation capability. In this study, the aim is to develop a liposomal nanocarrier formulation to enable the oral delivery of the vancomycin‐peptide derivative FU002. FU002 is a promising, resistance‐breaking, antibiotic which exhibits poor oral bioavailability, limiting its potential therapeutic use. To increase its oral bioavailability, FU002 is incorporated into tetraether lipid‐stabilized liposomes modified with cyclic cell‐penetrating peptides on the liposomal surface. This liposomal formulation shows strong binding to Caco‐2 cells without exerting cytotoxic effects in vitro. Pharmacokinetics studies in vivo in rats reveal increased oral bioavailability of liposomal FU002 when compared to the free drug. In vitro and in vivo antimicrobial activity of FU002 are preserved in the liposomal formulation. As a highlight, oral administration of liposomal FU002 results in significant therapeutic efficacy in a murine systemic infection model. Thus, the presented nanotechnological approach provides a promising strategy for enabling oral delivery of this highly active vancomycin derivative.
Lipid and Transcriptional Regulation in a Parkinson's Disease Mouse Model by Intranasal Vesicular and Hexosomal Plasmalogen‐Based Nanomedicines
Authors: Wu Yu , Wang Jieli , Deng Yuru , Angelov Borislav , Fujino Takehiko , Hossain Md. Shamim , Angelova Angelina
Published: February 2024

Plasmalogens (vinyl‐ether phospholipids) are an emergent class of lipid drugs against various diseases involving neuro‐inflammation, oxidative stress, mitochondrial dysfunction, and altered lipid metabolism. They can activate neurotrophic and neuroprotective signaling pathways but low bioavailabilities limit their efficiency in curing neurodegeneration. Here, liquid crystalline lipid nanoparticles (LNPs) are created for the protection and non‐invasive intranasal delivery of purified scallop‐derived plasmalogens. The in vivo results with a transgenic mouse Parkinson's disease (PD) model (characterized by motor impairments and α‐synuclein deposition) demonstrate the crucial importance of LNP composition, which determines the self‐assembled nanostructure type. Vesicle and hexosome nanostructures (characterized by small‐angle X‐ray scattering) display different efficacy of the nanomedicine‐mediated recovery of motor function, lipid balance, and transcriptional regulation (e.g., reduced neuro‐inflammation and PD pathogenic gene expression). Intranasal vesicular and hexosomal plasmalogen‐based LNP treatment leads to improvement of the behavioral PD symptoms and downregulation of the Il6, Il33, and Tnfa genes. Moreover, RNA‐sequencing and lipidomic analyses establish a dramatic effect of hexosomal nanomedicines on PD amelioration, lipid metabolism, and the type and number of responsive transcripts that may be implicated in neuroregeneration.
Development and Application of an Advanced Biomedical Material‐Silk Sericin
Authors: Wang Jian , Liu Huan , Shi Xiaolei , Qin Sumei , Liu Jingwei , Lv Qiying , Liu Jia , Li Qilin's , Wang Zheng , Wang Lin
Published: February 2024

Sericin, a protein derived from silkworm cocoons, is considered a waste product derived from the silk industry for thousands of years due to a lack of understanding of its properties. However, in recent decades, a range of exciting properties of sericin are studied and uncovered, including cytocompatibility, low‐immunogenicity, photo‐luminescence, antioxidant properties, as well as cell‐function regulating activities. These properties make sericin‐based biomaterials promising candidates for biomedical applications. This review summarizes the properties and bioactivities of silk sericin and highlights the latest developments in sericin in tissue engineering and regenerative medicine. Furthermore, the extended application of sericin in developing flexible electronic devices and 3D bioprinting is also discussed. It is believed that sericin‐based biomaterials have great potential of being developed into novel tissue engineering products and smart implantable devices for various medical applications toward improving clinical outcomes.
Acoustic Higher‐Order Topological Insulators Induced by Orbital‐Interactions
Authors: Gao Feng , Peng Yu‐Gui , Xiang Xiao , Ni Xiang , Zheng Chen , Yves Simon , Zhu Xue‐Feng , Alù Andrea
Published: February 2024

The discovery of higher‐order topological insulator metamaterials, in analogy with their condensed‐matter counterparts, has enabled various breakthroughs in photonics, mechanics, and acoustics. A common way of inducing higher‐order topological wave phenomena is through pseudo‐spins, which mimic the electron spins as a symmetry‐breaking degree of freedom. Here, this work exploits degenerate orbitals in acoustic resonant cavities to demonstrate versatile, orbital‐selective, higher‐order topological corner states. Type‐II corner states are theoretically investigated and experimentally demonstrated based on tailored orbital interactions, without the need for long‐range hoppings that has so far served as a key ingredient for Type‐II corner states in single‐orbital systems. Due to the orthogonal nature of the degenerate p orbitals, this work also introduces a universal strategy to realize orbital‐dependent edge modes, featuring high‐Q edge states identified in bulk bands. These findings provide an understanding of the interplay between acoustic orbitals and topology, shedding light on orbital‐related topological wave physics, as well as its applications for acoustic sensing and trapping.
Data Cleansing and Sub‐Unit‐Based Molecular Description Enable Accurate Prediction of The Energy Levels of Non‐Fullerene Acceptors Used in Organic Solar Cells
Authors: Zhang Ting , Yuk Lin Lai Joshua , Shi Mingzhe , Li Qing , Zhang Chen , Yan He
Published: February 2024

Non‐fullerene acceptors (NFAs) have recently emerged as pivotal materials for enhancing the efficiency of organic solar cells (OSCs). To further advance OSC efficiency, precise control over the energy levels of NFAs is imperative, necessitating the development of a robust computational method for accurate energy level predictions. Unfortunately, conventional computational techniques often yield relatively large errors, typically ranging from 0.2 to 0.5 electronvolts (eV), when predicting energy levels. In this study, the authors present a novel method that not only expedites energy level predictions but also significantly improves accuracy , reducing the error margin to 0.06 eV. The method comprises two essential components. The first component involves data cleansing, which systematically eliminates problematic experimental data and thereby minimizes input data errors. The second component introduces a molecular description method based on the electronic properties of the sub‐units comprising NFAs. The approach simplifies the intricacies of molecular computation and demonstrates markedly enhanced prediction performance compared to the conventional density functional theory (DFT) method. Our methodology will expedite research in the field of NFAs, serving as a catalyst for the development of similar computational approaches to address challenges in other areas of material science and molecular research.
Integrating Enzymes with Supramolecular Polymers for Recyclable Photobiocatalytic Catalysis
Authors: Ouyang Jingping , Zhang Zhenfang , Li Jian , Wu Changzhu
Published: February 2024

Chemical modifications of enzymes excel in the realm of enzyme engineering due to its directness, robustness, and efficiency; however, challenges persist in devising versatile and effective strategies. In this study, we introduce a supramolecular modification methodology that amalgamates a supramolecular polymer with Candida antarctica lipase B (CalB) to create supramolecular enzymes (SupEnzyme). This approach features the straightforward preparation of a supramolecular amphiphilic polymer (β‐CD@SMA), which was subsequently conjugated to the enzyme, resulting in a SupEnzyme capable of self‐assembly into supramolecular nanoparticles. The resulting SupEnzyme nanoparticles can form micron‐scale supramolecular aggregates through supramolecular and electrostatic interactions with guest entities, thus enhancing catalyst recycling. Remarkably, these aggregates maintain 80 % activity after seven cycles, outperforming Novozym 435. Additionally, they can effectively initiate photobiocatalytic cascade reactions using guest photocatalysts. As a consequence, our SupEnzyme methodology exhibits noteworthy adaptability in enzyme modification, presenting a versatile platform for various polymer, enzyme, and biocompatible catalyst pairings, with potential applications in the fields of chemistry and biology.
Build a High‐Performance All‐Solid‐State Lithium Battery through Introducing Competitive Coordination Induction Effect in Polymer‐Based Electrolyte
Authors: Wang Tenghui , Chen Butian , Liu Chong , Li Taiguang , Liu Xiangfeng
Published: February 2024

Polymer‐inorganic composite electrolytes (PICE) have attracted tremendous attention in all‐solid‐state lithium batteries (ASSLBs) due to facile processability. However, the poor Li+ conductivity at room temperature (RT) and interfacial instability severely hamper the practical application. Herein, we propose a concept of competitive coordination induction effects (CCIE) and reveal the essential correlation between the local coordination structure and the interfacial chemistry in PEO‐based PICE. CCIE introduction greatly enhances the ionic conductivity and electrochemical performances of ASSLBs at 30 °C. Owing to the competitive coordination (Cs+…TFSI−…Li+, Cs+…C−O−C…Li+ and 2,4,6‐TFA…Li…TFSI−) from the competitive cation (Cs+ from CsPF6) and molecule (2,4,6‐TFA: 2,4,6‐trifluoroaniline), a multimodal weak coordination environment of Li+ is constructed enabling a high efficient Li+ migration at 30 °C (Li+ conductivity: 6.25×10−4 S cm−1; tLi+=0.61). Since Cs+ tends to be enriched at the interface, TFSI− and PF6− in situ form LiF‐Li3N‐Li2O‐Li2S enriched solid electrolyte interface with electrostatic shielding effects. The assembled ASSLBs without adding interfacial wetting agent exhibit outstanding rate capability (LiFePO4: 147.44 mAh g−1@1 C and 107.41mAhg−1@2 C) and cycling stability at 30 °C (LiFePO4:94.65 %@200cycles@0.5 C; LiNi0.5Co0.2Mn0.3O2: 94.31 %@200 cycles@0.3 C). This work proposes a concept of CCIE and reveals its mechanism in designing PICE with high ionic conductivity as well as high interfacial compatibility at near RT for high‐performance ASSLBs.
Dithienoquinoxalineimide‐Based Polymer Donor Enables All‐Polymer Solar Cells Over 19 % Efficiency
Authors: Wang Zongtao , Wang Xin , Tu Lijun , Wang Hao , Du Mengzhen , Dai Tingting , Guo Qiang , Shi Yongqiang , Zhou Erjun
Published: February 2024

All‐polymer solar cells (all‐PSCs) have been regarded as one of the most promising candidates for commercial applications owing to their outstanding advantages such as mechanical flexibility, light weight and stable film morphology. However, compared to large amount of new‐emerging excellent polymer acceptors, the development of high‐performance polymer donor lags behind. Herein, a new D‐π‐A type polymer donor, namely QQ1, was developed based on dithienoquinoxalineimide (DTQI) as the A unit, benzodithiophene with thiophene‐conjugated side chains (BDTT) as the D unit, and alkyl‐thiophene as the π‐bridge, respectively. QQ1 not only possesses a strong dipole moment, but also shows a wide band gap of 1.80 eV and a deep HOMO energy level of −5.47 eV, even without halogen substituents that are commonly indispensable for high‐performance polymer donors. When blended with a classic polymer acceptor PY‐IT, the QQ1‐based all‐PSC delivers an outstanding PCE of 18.81 %. After the introduction of F‐BTA3 as the third component, a record PCE of 19.20 % was obtained, the highest value reported so far for all‐PSCs. The impressive photovoltaic performance originates from broad absorption range, reduced energy loss, and compact π–π stacking. These results provide new insight in the rational design of novel nonhalogenated polymer donors for further development of all‐PSCs.
Incentivized fake reviews: When cognitive reappraisal paves the way for an immoral journey
Authors: Malik Aaminah Zaman , Sadeghi R Kiarash , Paswan Audhesh , Kanwal Fizza
Published: February 2024

Recent studies explain how to detect fake reviews and their impacts on consumers and businesses. Despite the prevalence and significance of fake reviews, prior research has yet to fully explore the motivations and psychological mechanisms behind voluntary participation in writing fake reviews, especially in incentivized campaigns. This paper explains why consumers engage in the immoral act of writing fake reviews in return for free products. We investigate the interactive role of individuals' self‐focused motivations and cognitive reappraisal ability in diminishing consumers' moral emotions of guilt, subsequently influencing their intention to write incentivized reviews. Built on three studies, the findings reveal that customers' self‐focused motivations coupled with their ability to regulate emotions dissuade their feelings of guilt. Consequently, customers who experience downregulated emotions of guilt show a higher intention to write incentivized fake reviews. This study contributes to the existing literature by illustrating the driving factors toward writing incentivized fake reviews, especially by depicting the negative role of cognitive reappraisal. The study also has managerial implications indicating that such customer behavior can be avoided by fostering a sense of consideration toward others by making them aware about the impact of their actions.
An Investigation into the Larvicidal Activity of Biologically Synthesized Silver and Copper Oxide Nanoparticles Against Mosquito Larvae
Authors: Narayanan Lakshmanan , S R Suseem , Kamaraj Chinnaperumal
Published: February 2024

This study is primarily focused on the synthesis of silver and copper oxide nanoparticles utilizing the extract of Ipomoea staphylina plant and their larvicidal activity against specific larvae. Notably, Anopheles stephensi and Aedes aegypti are significant disease vectors responsible for transmitting diseases such as malaria, dengue fever, Zika virus, and chikungunya (Anopheles stephensi), and dengue and Zika (Aedes aegypti). These mosquitoes have a substantial impact on urban areas, influencing disease transmission dynamics. In an effort to control these larvae, we have pursued the synthesis of a herbal‐based nanomedicine derived from I. staphylina, a valuable herb in traditional medicine. Our successful synthesis of silver and CuO nanoparticles followed environmentally sustainable green chemistry methodologies. The I. staphylina plant extract played a dual role as a reducing agent and dopant, aligning with principles of sustainability. We employed X‐ray diffraction (XRD) analysis to validate the nanoparticle structure and size, while field‐emission scanning electron microscopy (FE‐SEM) revealed well‐defined nanostructures. Elemental composition was determined through energy‐dispersive X‐ray (EDX) analysis, and UV‐visible spectroscopy provided insights into the bandgap energy (3.15 eV for silver, 1.2 eV for CuO nanoparticles). These nanoparticles exhibited robust larvicidal activity, with CuO nanoparticles surpassing silver nanoparticles in terms of LC50 and LC90 values. Moreover, the developmental toxicity of CuO and Ag NPs was evaluated in zebrafish embryos as part of non‐target eco‐toxicological studies conducted in a standard laboratory environment. These findings underscore the potential utility of these nanoparticles as highly effective and environmentally friendly natural pesticides, offering cost‐effectiveness and ecological benefits.
In silico analysis of chromium‐reducing OXR genes derived from tannery effluent‐contaminated soil metagenome
Authors: Singh Ayushi , Patel Sanjay K. S. , Varma Ajit , Mandal Manabendra , Porwal Shalini
Published: February 2024

Tannery effluent waste comprises various potentially toxic metals, including chromium (Cr) with varying acute or chronic toxicity. Cr(VI) is known to be a category‐A carcinogen. Reduction of toxic Cr(VI) to Cr(III), which has lesser bioavailability, is one of the mechanisms used by many microbes to withstand Cr(VI) toxicity in the contaminated effluents. Oxidoreductase (OXRs) reduces toxic Cr(VI) to Cr(III); hence a thorough understanding of the OXRs is important for developing a suitable strategy to minimize Cr(VI) toxicity. Therefore, the OXR‐encoding genes were sequenced using metagenomic DNA shotgun sequencing from the tannery effluent‐contaminated soil. Six OXR‐encoding genes were expressed in Escherichia coli, and OXR activity was confirmed by in situ quantitative assays. The six proteins were subjected to phylogenetic and evolutionary analysis. Further, detailed structural analysis of the two OXRs, namely, OXR3 and OXR8 with lowest and highest activity respectively, were investigated in silico for structural characteristics. The results revealed that both the proteins were soluble FMN‐linked oxidoreductases. Eight conserved active site residues (Pro24, Thr26, Ala59, Tyr139, His178, Tyr180, His219, Tyr221, Arg269, and Lys360) in the enzyme OXR3 were predicted. Similarly, nine conserved active site residues (Pro20, Thr22, Ala55, Glu97, His191, Tyr193, Arg241, Cys334, and Arg335) were predicted in OXR8. The tertiary structure of OXR8 was an aldolase TIM barrel structure, like Thermus scotoductus chromate reductase. Docking with FMN revealed the involvement of all the nine predicted active site residues in FMN binding with Pro20, Thr22, and Cys334 as the most important ones.
SWOG S1820: A pilot randomized trial of the Altering Intake, Managing Bowel Symptoms Intervention in Survivors of Rectal Cancer
Authors: Sun Virginia , Guthrie Katherine A. , Crane Tracy E. , Arnold Kathryn B. , Colby Sarah , Freylersythe Sarah G. , Braun‐Inglis Christa , Topacio Roxanne , Messick Craig A. , Carmichael Joseph C. , Muskovitz Andrew A. , Nashawaty Mohammed , Bajaj Madhuri , Cohen Stacey A. , Flaherty Devin C. , O’Rourke Mark A. , Jones Lee , Krouse Robert S. , Thomson Cynthia A.
Published: February 2024

Background

Survivors of rectal cancer experience persistent bowel dysfunction after treatments. Dietary interventions may be an effective approach for symptom management and posttreatment diet quality. SWOG S1820 was a pilot randomized trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS‐RC) intervention for bowel dysfunction in survivors of rectal cancer.

Methods

Ninety‐three posttreatment survivors were randomized to the AIMS‐RC group (N = 47) or the Healthy Living Education attention control group (N = 46) after informed consent and completion of a prerandomization run‐in. Outcome measures were completed at baseline and at 18 and 26 weeks postrandomization. The primary end point was total bowel function score, and exploratory end points included low anterior resection syndrome (LARS) score, quality of life, dietary quality, motivation, self‐efficacy, and positive/negative affect.

Results

Most participants were White and college educated, with a mean age of 55.2 years and median time since surgery of 13.1 months. There were no statistically significant differences in total bowel function score by group, with the AIMS‐RC group demonstrating statistically significant improvements in the exploratory end points of LARS (p = .01) and the frequency subscale of the bowel function index (p = .03). The AIMS‐RC group reported significantly higher acceptability of the study.

Conclusions

SWOG S1820 did not provide evidence of benefit from the AIMS‐RC intervention relative to the attention control. Select secondary end points did demonstrate improvements. The study was highly feasible and acceptable for participants in the National Cancer Institute Community Oncology Research Program. Findings provide strong support for further refinement and effectiveness testing of the AIMS‐RC intervention.
Tumour‐associated macrophage‐derived DOCK7‐enriched extracellular vesicles drive tumour metastasis in colorectal cancer via the RAC1/ABCA1 axis
Authors: Chen Weiwei , Zhou Menghua , Guan Bingjie , Xie Bowen , Liu Youdong , He Jiang , Zhao Jingjing , Zhao Qian , Yan Dongwang
Published: February 2024

Background

Metastasis accounts for the majority of deaths among patients with colorectal cancer (CRC). Here, the regulatory role of tumour‐associated macrophages (TAMs) in CRC metastasis was explored.

Methods

Immunohistochemical (IHC) analysis of the TAM biomarker CD163 was conducted to evaluate TAM infiltration in CRC. Transwell assays and an ectopic liver metastasis model were established to evaluate the metastatic ability of tumour cells. RNA sequencing (RNA‐seq) and liquid chromatography‒mass spectrometry (LC‒MS) were applied to identify the differentially expressed genes and proteins in CRC cells and in TAM‐derived extracellular vesicles (EVs). Cholesterol content measurement, a membrane fluidity assay and filipin staining were performed to evaluate cholesterol efflux in CRC cells.

Results

Our results showed that TAM infiltration is positively correlated with CRC metastasis. TAMs can facilitate the migration and invasion of MC‐38 and CT‐26 cells via EVs. According to the RNA‐seq data, TAM‐EVs increase cholesterol efflux and enhance membrane fluidity in CRC cells by regulating ABCA1 expression, thus affecting the motility of CRC cells. Mechanistically, DOCK7 packaged in TAM‐EVs can activate RAC1 in CRC cells and subsequently upregulate ABCA1 expression by phosphorylating AKT and FOXO1. Moreover, IHC analysis of ABCA1 in patients with liver‐metastatic CRC indicated that ABCA1 expression is significantly greater in metastatic liver nodules than in primary CRC tumours.

Conclusions

Overall, our findings suggest that DOCK7 delivered via TAM‐EVs could regulate cholesterol metabolism in CRC cells and CRC cell metastasis through the RAC1/AKT/FOXO1/ABCA1 axis. DOCK7 could thus be a new therapeutic target for controlling CRC metastasis.
Geospatial environmental complexity, spatial brain volume, and spatial behavior across the Alzheimer's disease spectrum
Authors: Shin Naewoo , Rodrigue Karen M. , Yuan May , Kennedy Kristen M.
Published: February 2024

INTRODUCTION

Understanding impact of environmental properties on Alzheimer's disease (AD) is paramount. Spatial complexity of one's routinely navigated environment is an important but understudied factor.

METHODS

A total of 660 older adults from National Alzheimer's Coordinating Center (NACC) dataset were geolocated and environmental complexity index derived from geospatial network landmarks and points‐of‐interest. Latent models tested mediation of spatial navigation‐relevant brain volumes and diagnosis (cognitively‐healthy, mild cognitive impairment [MCI], AD) on effect of environmental complexity on spatial behavior.

RESULTS

Greater environmental complexity was selectively associated with larger allocentric (but not egocentric) navigation‐related brain volumes, lesser diagnosis of MCI and AD, and better spatial behavioral performance, through indirect hierarchical mediation.

DISCUSSION

Findings support hypothesis that spatially complex environments positively impact navigation neural circuitry and spatial behavior function. Given the vulnerability of these very circuits to AD pathology, residing in spatially complex environments may be one factor to help stave off the brain atrophy that accompanies spatial navigation deficits across the AD spectrum.
A healthier movement behavior profile is associated with body‐congruent food choices through self‐determined motivations to exercise and regulate eating
Authors: Carraça Eliana Veiga , Rodrigues Bruno , Sánchez‐Oliva David
Published: February 2024

Physical activity (PA) facilitates eating behavior regulation, in part through self‐determined motivations to regulate PA and eating behaviors. However, different patterns of PA and sedentary behavior (SB) accumulation appear to have distinct effects on several health outcomes and might therefore be differently related to eating self‐regulation. This study aimed to identify different PA/SB profiles, and test motivational routes underlying associations between these profiles and eating. A total of 297 adults (age: 34.5 ± 10.6 years; BMI: 23.2 ± 3.4 kg/m2) filled a psychometric battery of validated questionnaires to assess PA, SB, motivations to exercise and eating, and intuitive eating dimensions. Latent Profile Analysis and Preacher and Hayes Mediation Procedures were conducted. A 3‐profiles model was retained as the best solution (++sitting/‐PA, n = 89; ++PA/‐sitting, n = 44; +PA/+sitting, n = 164). Participants in the ++PA/‐Sitting profile showed higher self‐determined motivations to exercise (ps < 0.001) and regulate eating (ps < 0.05), mostly when compared to the ++Sitting/‐PA profile. Mediation analyses showed that participants in the ++PA/‐Sitting profile (vs. ++Sitting/‐PA) made more body‐congruent food choices, in part through a serial mediation effect of self‐determined motivations to exercise and eating (Estimate: 0.25 (0.07), 95% CI: 0.13; 0.40). All analyses were adjusted for age, gender, and BMI. Results extend prior evidence, showing that motivations underpinning PA/eating have better quality when greater levels of PA are combined with lower sitting time, and by showing that self‐determined motivations partly mediate the effects of different PA/SB profiles on eating regulation. These findings have implications for future interventions promoting active lifestyles.
An examination of differences in epigenetic methylation of saliva type samples based on collection method
Authors: Ghemrawi Mirna , Fernandez‐Tejero Nicole , Vaquero Lia , Wanna Amani , Carmel Justin H. , McCord Bruce
Published: February 2024

In the context of forensic casework, it is imperative to both establish a DNA profile from biological specimens and accurately identify the specific bodily fluid source. To achieve this, DNA methylation markers have been developed for the differentiation of blood, semen, vaginal epithelial secretions, and saliva samples. Saliva, alternatively referred to as oral fluid, is recognized for its heterogeneous cellular composition, characterized by a mixture of epithelial, leukocytic, and bacterial cells. Consequently, our research has revealed variations in methylation percentages that correlate with the method employed for collecting saliva samples. To investigate these concepts, we scrutinized four CpG markers situated within or in proximity to the BCAS4, SLC12A8, SOX2OT, and FAM43A genes. Subsequently, we designed primers based on bioinformatically transformed reference sequences for these markers and rigorously assessed their quality by examining dimer and hairpin formation, melting temperature, and specificity. These loci were identified as saliva markers based on either buccal swabs or spit collection. Yet, there has been minimal or no research conducted to explore the variations in methylation between different collection methods. For this study, buccal, lip, tongue, spit, and nasal swabs were collected from 20 individuals (N = 100). Mock forensic samples, which include chewing gum (N = 10) and cigarettes (N = 10), were also tested. DNA was extracted, bisulfite converted, then amplified using in‐house designed assays, and pyrosequenced. The methylation levels were compared to other body fluids (semen, blood, vaginal epithelia, and menstrual blood [N = 32]). A total of 608 pyrosequencing results demonstrated that sampling location and collection method can greatly influence the level of methylation, highlighting the importance of examining multiple collection/deposition methods for body fluids when developing epigenetic markers.
Clinical outcomes of cetuximab‐based treatment for distant metastatic head and neck squamous cell carcinoma: A real‐world study using Taiwan Head Neck Society registry database
Authors: Lu Hsueh‐Ju , Hsieh Meng‐Che , Wang Hung‐Ming , Hsieh Jason Chia‐Hsun , Yen Chia‐Jui , Wu Shang‐Yin , Huang Huai‐Cheng , Wang Hui‐Ching , Chu Pen‐Yuan , Chen Tien‐Hua , Chien Chih‐Yen , Huang Tai‐Lin , Chang Yi‐Fang , Hua Chun‐Hung , Lien Ming‐Yu , Chen Jo‐Pai , Lu Wei‐Chen , Lin Jin‐Ching , Wang Chen‐Chi , Liu Yi‐Chun , Yang Muh‐Hwa , Lou Pei‐Jen
Published: February 2024

Background

For R/M HNSCC, the differences in prognosis and treatment options between distant metastasis (DM) and locoregional recurrence, especially in the DM group, remain unclear.

Methods

From the Taiwan Head Neck Society registry database, patients who were diagnosed with R/M HNSCC and received cetuximab‐based frontline therapy were collected for analysis.

Results

Among the enrolled patients, 59.3% (491/827) belonged to the DM group. The DM group had less primary site of oral cavity, less betel nut chewing, higher lactate dehydrogenase (LDH) levels, and higher LDH/albumin ratio compared with the non‐DM group. For the patients with primary site of oral cavity and current smokers, DM coexisted with poorer outcomes. In the DM group, EXTREME‐like regimen was more suitable for older patients, those with elevated LDH, and those with higher LDH/albumin ratio than TPExtreme‐like regimen.

Conclusion

DM coexisted with poorer prognosis in certain groups. LDH‐associated biomarkers may aid treatment options for DM patients.
Portal Hypertensive Gastropathy in Children with Extrahepatic Portal Venous Obstruction: Role of Variceal Obliteration by Endoscopic Sclerotherapy and Helicobacter pylori Infection
Authors: Yachha S. K. , Ghoshal U. C. , Gupta R. , Sharma B. C. , Ayyagari A.
Published: February 2024

We aimed to determine the frequency of portal hypertensive gastropathy (PHG) in children with extrahepatic portal venous obstruction (EHPVO) and to find out the role of esophageal variceal obliteration by endoscopic injection sclerotherapy (EIS) and Helicobacter pylori (H. pylori) infection in the pathogenesis of PHG. Twenty consecutive children were studied before EIS and 20 after esophageal varices obliteration. Diagnosis of PHG was established by endoscopic assessment. Helicobacter pylori infection was diagnosed by rapid urease test, H. pylori culture, smear, and histopathologic examination of antral biopsy specimens. Portal hypertensive gastropathy was characterized and graded by endoscopy according to previously established criteria. In the pre‐EIS group, eight (40%) had PHG (mild in all) compared with 16 (80%; mild in eight, severe in eight) in the post‐EIS group (p < 0.05). Portal hypertensive gastropathy was more extensive in the post‐EIS group. There was no significant difference between frequency of gastric varices and H. pylori infection in the pre‐EIS and post‐EIS groups. We conclude that PHG is common in children with EHPVO; its frequency, extent, and severity increase after esophageal variceal obliteration by EIS, and H. pylori infection does not play any role in its development.
Genotyping of Hepatitis C Virus: Coinfection by Multiple Genotypes Detected in Children with Chronic Posttransfusion Hepatitis C
Authors: Matsubara Takako , Sumazaki Ryo , Shin Kenji , Nagai Yoji , Takita Hitoshi
Published: February 2024

The distribution of genotypes of the hepatitis C virus (HCV) was studied in 24 children with chronic posttransfusion hepatitis C. Genotypes were determined by reverse transcription‐nested polymerase chain reaction with type‐specific primers. Twenty (83%) were infected by a single genotype: 14 by type II [1b], 3 by III [2a], and 3 IV [2b]. Four (17%) were coinfected by two genotypes. The amount of blood transfusion given to the patients infected by multiple genotypes was significantly larger than to those infected by a single genotype (mean ± SD, 15.2 ± 14.4 vs 78.6 ± 42.0 U). Three of the four patients infected by multiple genotypes were considered to be immunocompromised by anticancer therapy for malignant disease. Eighteen patients showed a raised level of alanine aminotransferase throughout the follow‐up, while the remaining six patients (three of type II [1b], two of IV [2b], and one of III [2a] + IV [2b]) achieved biochemical remission. Liver biopsy was performed on 19 patients. Compared to those with type III [2a] or IV [2b], those with type II [1b] appeared to show more severe histological changes with higher histological activity index scores, although there was no significant difference. The positive rates of antibody to C100‐3 or 5‐1‐1 in patients with type III [2a] or IV [2b] were lower than in those with type II [1b] (33 and 33 vs 43 and 50%), whereas the antibody to C33C or C22‐3 was detected in nearly all patients regardless of their genotypes. In the present study, we found a high incidence of multiple‐genotype infection among children with chronic posttransfusion hepatitis C.
IgA Endomysium Antibodies on Human Umbilical Cord: An Excellent Diagnostic Tool for Celiac Disease in Childhood
Authors: Kolho Kaija‐Leena , Savilahti Erkki
Published: February 2024

Background:

An improvement in screening for celiac disease has recently been described that uses human umbilical cord as a substitute for monkey esophagus to determine IgA endomysium antibodies in adults. As using monkey esophagus is ethically questionable for large‐scale screening, we studied whether substitution of umbilical cord would be suitable for pediatric patients as well.

Methods:

Serum from 53 children with untreated celiac disease, 22 in remission and 13 on challenge, were screened for antigliadin IgA, antigliadin IgG, and IgA reticulin antibodies, in addition to IgA endomysium antibodies tested both on monkey esophagus and on human umbilical cord. Controls included 20 patients with cow‐milk‐sensitive enteropathy, 23 with inflammatory bowel disease, and 23 with diabetes mellitus, and 48 patients who were biopsied to exclude celiac disease either because of positive gliadin antibody test or disturbed growth.

Results:

Sensitivity (0.94) and specificity (1.0) were similar for umbilical cord and esophageal determinations in active celiac disease. Both substrates detected identical positive cases and neither gave false‐positive results. In celiac patients on a gluten‐free diet, endomysium antibodies with either substrate were positive in seven identical cases and negative in 15 of 22 cases. Correlations with reticulin antibodies were comparable with human umbilical cord and monkey esophagus (0.83 and 0.85, respectively; Spearman Correlation Scction Pair‐Wise deletion).

Conclusions:

Human umbilical cord is an excellent substitute for monkey esophagus to determine endomysium antibodies in celiac diagnosis in children and adolescents.
Enteric Cryptosporidiosis in Pediatric HIV Infection
Authors: Guarino Alfredo , Castaldo Annunziata , Russo Stefania , Spagnuolo Maria Immacolata , Canani Roberto Berni , Tarallo Luigi , DiBenedetto Linda , Rubino Armido
Published: February 2024

Background

Enteric cryptosporidiosis is a frequent problem in adults with human immunodeficiency virus (HIV) infection, but little is known of its features in children. The aim of this study was to investigate the incidence and the clinical features of cryptosporidiosis in HIV‐infected children.

Methods

Thirty‐five children with symptomatic HIV infection were screened every 2 months, and in case of diarrhea, for the presence of Cryptosporidium. Intestinal function tests were performed, and the fecal osmotic gap was measured in children with cryptosporidiosis.

Results

Seventy episodes of diarrhea occurred in 16 children in a median period of 17 months. Cryptosporidium was detected in five cases, all with full‐blown acquired immunodeficiency syndrome. Cryptosporidiosis was significantly more protracted than any other form of diarrhea and was associated with dehydration and severe weight loss. Intestinal function was not modified during cryptosporidiosis. Osmotic gap values were consistent with secretory rather than osmotic diarrhea. In four cases, recovery was observed without specific treatment.

Conclusions

Enteric cryptosporidiosis is a severe problem in advanced stages of HIV infection. It does not induce intestinal malabsorption. It induces diarrhea of secretory type. Recovery may be observed independently of therapy.
Cisapride in Pediatric Gastroesophageal Reflux
Authors: Scott R. B. , Ferreira C. , Smith L. , Jones A. B. , Machida H. , Lohoues M. J. , Roy C. C.
Published: February 2024

Background:

Gastroesophageal reflux is a common condition that in infants may lead to serious complication. This study assessed the efficacy and safety of oral cisapride suspension in the treatment of children 6 weeks to 2 years old with daily regurgitant reflux.

Methods:

A randomized, prospective, double‐blind, placebo‐controlled clinical trial was conducted at three study sites. After a 1 week baseline assessment, 45 infants 6 weeks to 2 years old were randomized to a double‐blind trial in which they received a 6 week course of cisapride (0.2 mg/kg q6h) or a placebo suspension. Efficacy was assessed with 24 hour esophageal pH monitoring, esophageal manometry, and esophageal biopsy before and after the treatment period. A diary of regurgitation frequency and severity was kept by the parents. Safety was assessed by adverse event monitoring and standard laboratory measurements.

Results:

Compared with placebo, cisapride significantly (p < 0.05) reduced the mean duration of upright and supine reflux episodes. Compared to baseline, cisapride significantly reduced the mean duration of the longest reflux episode, and placebo increased the mean number of reflux episodes longer than 5 minutes. Cisapride was not significantly different from placebo for the following mean measurements: percent of total time pH <4, number of reflux episodes, lower esophageal sphincter pressure, swallow pressure, regurgitation frequency or global evaluation scores.

Conclusions:

Cisapride is a safe, well tolerated prokinetic agent that improves the esophageal clearance of refluxed gastric acid in children under the age of 2 years.
Can the Histologic Changes of Cystic Fibrosis‐Associated Hepatobiliary Disease be Predicted by Clinical Criteria?
Authors: Potter Carol J. , Fishbein Mark , Hammond Sue , McCoy Karen , Qualman Steve
Published: February 2024

Background:

Correlation between clinical parameters and histology changes in cystic fibrosis liver disease has not been documented. The purpose of this study was to determine the histologic spectrum of cystic fibrosis liver disease and the degree to which a clinical scoring system can identify subjects with significant histologic abnormalities.

Methods:

We reviewed the predictive value of physical examination, biochemical parameters, and a clinical liver score, incorporating physical examination and biochemical parameters, in predicting significant abnormalities of liver histology in 43 cystic fibrosis patients who underwent hepatic biopsy. Biopsies were scored by two masked pathologists for fibrosis, inflammation, inspissation, fatty infiltration, and congestion.

Results:

Significant histologic disease was present in 56% of patients despite little biochemical or physical examination evidence of disease. No single parameter used in the scoring system predicted the type or degree of the liver disease. The clinical liver score had a sensitivity of 85% and a specificity of 82% in predicting significant histologic changes, yet it was unable to predict the specific lesion.

Conclusions:

Significant histologic liver disease is common in cystic fibrosis, although the exact nature of the lesion cannot be predicted without liver biopsy. A clinical liver score that was developed for this may be useful in determining which patients require more definitive evaluation.
Prospective Significance of Antiendomysium Antibody Positivity in Subsequently Verified Celiac Disease
Authors: Korponay‐Szabó Ilma R. , Kovács Judit B. , Lörincz Margit , Gorácz Gyula , Szabados Katalin , Balogh Márta
Published: February 2024

Background:

In order to assess their long‐term predictability for the diagnosis of celiac disease, antiendomysium antibody results were compared with the outcome of the Interlaken diagnostic process.

Methods:

Prospective gluten challenge was performed in 153 children with previously diagnosed flat small‐intestine mucosa. In 90 patients (Group A), endomysium antibodies were initially positive, in seven (Group B) they were negative, and 56 patients (Group C) had no initial serological results. In IgA‐deficient persons, IgG antibodies were also assayed, both by the immunofluorescent method.

Results:

Histological relapse rates were 100% (90/90), 14.3% (1/7), and 76.8% (43/56), p < 0.001, in Groups A, B, and C, respectively. Each patient with relapse also exhibited endomysium antibody positivity during the challenge. Patients in whom celiac disease could be finally ruled out remained consistently endomysium‐antibody negative. The celiac disease patient in Group B had severe secondary immunoglobulin deficiency at entry, which explained the initial negativity. Diagnosis based on antiendomysium antibody positivity and flat mucosa gave a higher applicability (92.8 vs. 50.3%) and reliability (relapse rate 100 vs. 89.6%) than the 1990 European Society of Paediatric Gastroenterology and Nutrition (ESPGAN) criteria among these patients.

Conclusions:

Endomysium antibody positivity at presentation has been found to be as useful as gluten challenge in the diagnosis of celiac disease, even in patients under the age of 2 years. Challenge is still advisable in patients with a flat small intestinal mucosa when antiendomysium antibody results are negative or have not been done, as among these patients significantly lower relapse rates were found.