bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nrf2/Keap1/ARE regulation by plant secondary metabolites: a new horizon in brain tumor management
Authors: Dewanjee Saikat , Bhattacharya Hiranmoy , Bhattacharyya Chiranjib , Chakraborty Pratik , Fleishman Joshua , Alexiou Athanasios , Papadakis Marios , Jha Saurabh Kumar 
Published: October 2024

AbstractBrain cancer is regarded as one of the most life-threatening forms of cancer worldwide. Oxidative stress acts to derange normal brain homeostasis, thus is involved in carcinogenesis in brain. The Nrf2/Keap1/ARE pathway is an important signaling cascade responsible for the maintenance of redox homeostasis, and regulation of anti-inflammatory and anticancer activities by multiple downstream pathways. Interestingly, Nrf2 plays a somewhat, contradictory role in cancers, including brain cancer. Nrf2 has traditionally been regarded as a tumor suppressor since its cytoprotective functions are considered to be the principle cellular defense mechanism against exogenous and endogenous insults, such as xenobiotics and oxidative stress. However, hyperactivation of the Nrf2 pathway supports the survival of normal as well as malignant cells, protecting them against oxidative stress, and therapeutic agents. Plants possess a pool of secondary metabolites with potential chemotherapeutic/chemopreventive actions. Modulation of Nrf2/ARE and downstream activities in a Keap1-dependant manner, with the aid of plant-derived secondary metabolites exhibits promise in the management of brain tumors. Current article highlights the effects of Nrf2/Keap1/ARE cascade on brain tumors, and the potential role of secondary metabolites regarding the management of the same.
Innovative nebulization delivery of lipid nanoparticle-encapsulated siRNA: a therapeutic advance for Staphylococcus aureus-induced pneumonia
Authors: Meng Meiqi , Li Yue , Wang Jiachao , Han Xiaonan , Wang Xuan , Li Hongru , Xiang Bai , Ma Cuiqing 
Published: October 2024

Abstract
Background
Integrin α5β1 plays a crucial role in the invasion of nonphagocytic cells by Staphylococcus aureus (S. aureus), thereby facilitating infection development. Lipid nanoparticles (LNPs) serve as an effective vehicle for delivering small interfering ribonucleic acids (siRNA) that represent a method to knockdown integrin α5β1 in the lungs through nebulization, thereby potentially mitigating the severity of S. aureus pneumonia. The aim of this study was to harness LNP-mediated targeting to precisely knockdown integrin α5β1, thus effectively addressing S. aureus-induced pneumonia.

Methods
C57 mice (8 week-old females) infected with S. aureus via an intratracheal nebulizing device were utilized for the experiments. The LNPs were synthesized via microfluidic mixing and characterized by their size, polydispersity index, and encapsulation efficiency. Continuous intratracheal nebulization was employed for consistent siRNA administration, with the pulmonary function metrics affirming biosafety. The therapeutic efficacy of LNP-encapsulated siRNAs against pneumonia was assessed through western blotting, bacterial count measurement, quantitative polymerase chain reaction, and histological analyses.

Results
LNPs, which have an onion-like structure, retained integrity post-nebulization, ensuring prolonged siRNA stability and in vivo safety. Intratracheal nebulization delivery markedly alleviated the severity of S. aureus-induced pneumonia, as indicated by reduced bacterial load and bolstered immune response, thereby localizing the infection to the lungs and averting systemic dissemination.

Conclusions
Intratracheal nebulization of LNP-encapsulated siRNAs targeting integrin α5β1 significantly diminished the S. aureus-mediated cellular invasion and disease progression in the lungs, presenting a viable therapeutic approach for respiratory infections.
Very pronounced bowel sparing during radiation therapy for anal carcinoma using a natural spacer (Myoma) – a case report
Authors: Hoeng L. , Exeli A. K. , Krombach G. A. , Schwandner T. , Agolli L. , Habermehl D. 
Published: October 2024

Abstract
Background
Using dose-painted intensity-modulated radiation therapy, specific dose volume constraints or implantation of tissue expanders prior to radiotherapy are validated options for reducing radiation dose on the bowel and therefore minimizing acute gastrointestinal toxicity during chemoradiation for anorectal malignancies. We describe the rare case of a female patient with a locally advanced anal carcinoma where a large myomatous uterus served as a natural spacer to protect the bowel during radiation therapy.

Case presentation
Initially the patient presented with anal pain, proctoscopy followed by an excisional biopsy confirmed the diagnosis of a squamous cell carcinoma of the anus. Imaging examination showed a locally advanced tumor and in addition a large uterus with typical leiomyomas up to 11.5 cm in diameter. The patient underwent chemoradiation; because of the large leiomyomas there was almost no dose burden for the small intestine and therefore practically no gastrointestinal toxicity.

Conclusion
As we know, this report describes the situation that a large myomatous uterus served as a natural spacer during radiation therapy in a way that is unique to date.
Low shear stress protects chondrocytes from IL-1β-induced apoptosis by activating ERK5/KLF4 signaling and negatively regulating miR-143-3p
Authors: Zhao Jun , Xia Yayi 
Published: October 2024

Abstract
Objective
This study investigated the protective effects of low fluid shear stress (FSS ≤ 2 dyn/cm²) against interleukin-1β (IL-1β)-induced chondrocyte apoptosis and explored the underlying molecular mechanisms.

Methods
Chondrocytes were cultured under four conditions: control, IL-1β stimulation, low FSS, and combined low FSS + IL-1β stimulation. Apoptosis was assessed using Hoechst staining and flow cytometry. Western blotting determined the expression of caspase-3 (CASP3), caspase-8 (CASP8), and NF-κB p65. Quantitative real-time PCR measured miR-143-3p expression. The roles of miR-143-3p and the extracellular signal-regulated kinase 5 (ERK5)/Krüppel-like factor 4 (KLF4) signaling pathway were further investigated using miR-143-3p mimics and inhibitors, an ERK5 inhibitor, and a KLF4 overexpression vector.

Results
IL-1β induced significant chondrocyte apoptosis, which was markedly inhibited by low FSS. Mechanistically, low FSS suppressed miR-143-3p expression, thereby enhancing ERK5 signaling. This activated ERK5 subsequently upregulated KLF4 expression, further mitigating IL-1β-induced damage. Importantly, miR-143-3p overexpression under low FSS conditions exacerbated IL-1β-induced apoptosis, while miR-143-3p inhibition attenuated it. Consistent with this, ERK5 inhibition augmented IL-1β-induced apoptosis, whereas KLF4 overexpression suppressed it.

Conclusion
Low FSS protects chondrocytes from IL-1β-induced apoptosis by suppressing miR-143-3p and activating the ERK5/KLF4 signaling pathway. This study reveals a novel mechanism by which mechanical stimulation protects cartilage.
Large-scale annotation of biochemically relevant pockets and tunnels in cognate enzyme–ligand complexes
Authors: Vavra O. , Tyzack J. , Haddadi F. , Stourac J. , Damborsky J. , Mazurenko S. , Thornton J. M. , Bednar D. 
Published: October 2024

AbstractTunnels in enzymes with buried active sites are key structural features allowing the entry of substrates and the release of products, thus contributing to the catalytic efficiency. Targeting the bottlenecks of protein tunnels is also a powerful protein engineering strategy. However, the identification of functional tunnels in multiple protein structures is a non-trivial task that can only be addressed computationally. We present a pipeline integrating automated structural analysis with an in-house machine-learning predictor for the annotation of protein pockets, followed by the calculation of the energetics of ligand transport via biochemically relevant tunnels. A thorough validation using eight distinct molecular systems revealed that CaverDock analysis of ligand un/binding is on par with time-consuming molecular dynamics simulations, but much faster. The optimized and validated pipeline was applied to annotate more than 17,000 cognate enzyme–ligand complexes. Analysis of ligand un/binding energetics indicates that the top priority tunnel has the most favourable energies in 75% of cases. Moreover, energy profiles of cognate ligands revealed that a simple geometry analysis can correctly identify tunnel bottlenecks only in 50% of cases. Our study provides essential information for the interpretation of results from tunnel calculation and energy profiling in mechanistic enzymology and protein engineering. We formulated several simple rules allowing identification of biochemically relevant tunnels based on the binding pockets, tunnel geometry, and ligand transport energy profiles.Scientific contributionsThe pipeline introduced in this work allows for the detailed analysis of a large set of protein–ligand complexes, focusing on transport pathways. We are introducing a novel predictor for determining the relevance of binding pockets for tunnel calculation. For the first time in the field, we present a high-throughput energetic analysis of ligand binding and unbinding, showing that approximate methods for these simulations can identify additional mutagenesis hotspots in enzymes compared to purely geometrical methods. The predictor is included in the supplementary material and can also be accessed at https://github.com/Faranehhad/Large-Scale-Pocket-Tunnel-Annotation.git. The tunnel data calculated in this study has been made publicly available as part of the ChannelsDB 2.0 database, accessible at https://channelsdb2.biodata.ceitec.cz/.
Acceptability of “DIDE”, a mobile application designed at facilitating care adherence of patients with substance use disorder
Authors: Stocker Antoine , Navarro Nicolas , Schmitt Laurent , Delagnes Marc , Doualle Aurélie , Mallard Valérie , Entajan Flora , Guivarc’h Karine , Masse Patricia , Chaigneau Lilian , Bonneau Baptiste , Lapeyre-Mestre Maryse , Arbus Christophe , Yrondi Antoine , Salles Juliette 
Published: October 2024

Abstract
Background
Attrition continues to be a major hurdle for addiction treatment. Through the prism of the attachment theory, this phenomenon can be understood as a manifestation of the patient’s insecure attachment style, needing a highly-responsive care delivery. We developed an electronic health mobile application, co-designed with patients, aimed at helping healthcare teams respond to their patients’ needs, and fostering adherence to care. This acceptability study evaluated patients everyday use of the application for eight weeks, assessing their satisfaction with the system, and its integration within professionals’ current practice in our center.

Methods
This single-center, prospective study was conducted between January 2022 and December 2022. 24 adult patients with any type of addiction were included. They were granted access to the application for eight weeks, and were invited to complete the System Usability Scale questionnaire regarding their satisfaction with application’s usability at the end of the study. The application uses active self-reports, which are later discussed with the healthcare team, and foster both the working alliance and the decision-making process.

Results
17 patients out of 24 reached the primary endpoint. On average, over the eight-weeks period, patients logged in the application 38.2 times, and sent 5.9 messages to the healthcare team. Interestingly, 64.3% of the user logins were recorded outside of our center’s working hours (either from 5 p.m. to 9 a.m., or during week-ends and bank holidays), and 70.8% of the patients logged into the application at least one time between 10 p.m. and 8 a.m. 18 patients completed the System Usability Scale questionnaire, which averaged a score of 81.8 out of 100. Healthcare professionals logged in the application’s messaging system 4.5 times a day on average.

Conclusions
This preliminary study shows promising results, as patients engaged well with various components of the application. It was moreover possible for healthcare workers in our center to integrate this tool in their daily activities. More work is needed to better understand the various patients’ needs regarding the application, further strengthen their adherence to the intervention, and understand professionals’ motivations to use the application.

Trial registration
ClinicalTrials.gov, Identifier: NCT04659954. Registered 09 December 2020, https://clinicaltrials.gov/study/NCT04659954.
Services for perinatal patients with opioid use disorder: a comprehensive Baltimore City-wide 2023 assessment
Authors: Ratner Jessica A. , Kirschner Jennifer H. , Spencer Brittney , Terplan Mishka 
Published: October 2024

Abstract
Background
Overdose is a leading cause of maternal mortality; in response, maternal mortality review committees have recommended expanding substance use disorder (SUD) screening, improving collaboration between obstetric and SUD treatment providers, and reducing fragmentation in systems of care. We undertook an analysis of the perinatal SUD treatment landscape in Baltimore, Maryland in order to identify barriers to treatment engagement during pregnancy and the postpartum period and guide system improvement efforts.

Methods
We conducted a survey of seven birthing hospitals, 31 prenatal care practices, and 108 SUD treatment providers in Baltimore from April-June 2023. Organizations were asked to quantify care for perinatal patients with opioid use disorder (OUD) as well as about screening, service availability, referral practices, and support needed to improve care.

Results
61% of the 145 contacted organizations responded. Birthing hospitals reported caring for pregnant persons with OUD with greater frequency than prenatal care practices or SUD treatment programs. Most birthing hospitals and prenatal care practices reported screening for OUD at intake, but the minority reported using validated tools. Service availability varied by type of organization and type of service. In general, prenatal care practices offered the fewest number of SUD-related services. Most SUD treatment programs that offered buprenorphine or methadone to the general population also offered these medications to pregnant patients. Withdrawal management for comorbid alcohol/benzodiazepine use disorders during pregnancy was more limited. The majority of birthing hospitals and prenatal care practices reported offering neither direct naloxone distribution nor prescriptions. Few SUD treatment programs offered tailored services for perinatal patients or for parents of young children, and many programs do not permit children onsite. Respondents reported high levels of interest in education and consultative support on SUD treatment in pregnancy within obstetric settings and on pregnancy-related medical concerns within SUD programs.

Conclusions
This project provides a comprehensive picture of services available for treatment of perinatal OUD in a major US city. Results have served as a guide for ongoing citywide system improvement efforts by our project team and offer a model for other jurisdictions hoping to strengthen services for perinatal OUD and reduce maternal mortality.
Racial/Ethnic Disparities in Hospitalization Outcomes by Palliative Care Utilization and Trends Among Women With Metastatic Breast Cancer in the United States
Authors: Jackson Inimfon , Lu Qian , Tripathy Debasish 
Published: October 2024

PURPOSE
We examined the trends in palliative care utilization, racial/ethnic disparities in hospitalization outcomes among adult women with a diagnosis of metastatic breast cancer (MBC), and effect modification by palliative care utilization.

METHODS
Retrospective cohort analyses were conducted using the Agency for Healthcare Research and Quality sponsored Healthcare Cost and Utilization Project—National Inpatient Sample database from 2016 to 2020. Regression analyses were used to evaluate palliative care trends, and the association between race/ethnicity and in-hospital mortality, length of stay, total hospital charges, and discharge disposition. Stratified analyses were conducted by palliative care use.

RESULTS
Palliative care consultations in the study population increased from 16.4% in 2016 to 20.3% in 2020. Black (adjusted odds ratio [AOR], 1.25 [95% CI, 1.16 to 1.34]) and Hispanic (AOR, 1.12 [95% CI, 1.01 to 1.23]) female patients with MBC had higher in-hospital mortality compared with the White patients. Among those who received palliative care, Blacks had similar odds (AOR, 1.08 [95% CI, 0.97 to 1.20]) of in-hospital mortality when compared with Whites. Black women were more likely to have longer hospital stays relative to White women. Although Black women had similar odds (AOR, 0.98 [95% CI, 0.92 to 1.04]) of discharge to a short-term/skilled nursing facility versus routine discharge compared with White women, Blacks who received palliative care had 19% (95% CI, 0.70 to 0.95) lower odds of discharge to a facility.

CONCLUSION
Our findings emphasize the importance of palliative care use among patients with MBC and highlight the need to raise awareness of its benefits, especially in minority populations. Further studies are needed to explore ways to narrow the gap in existing disparities and to test these interventions on care metrics and patient outcomes.
The hearts of large mammals generate higher pressures, are less efficient and use more energy than those of small mammals
Authors: Snelling Edward P. , Seymour Roger S. 
Published: October 2024

ABSTRACT
A prevailing assumption in the cardiovascular field is that the metabolic rate of the heart is a constant proportion of a mammal's whole-body aerobic metabolic rate. In this Commentary, we assemble previously published cardiovascular, metabolic and body mass data from matched terrestrial mammalian species, at rest and during heavy exercise, and reveal scaling relationships that challenge this assumption. Our analyses indicate that the fractional metabolic cost of systemic perfusion compared with whole-body metabolic rate increases significantly with body size among resting mammals, from ∼2.5% in a mouse to ∼10% in an elephant. We propose that two significant body size-dependent effects contribute to this conclusion; namely, that larger species generate higher mean systemic arterial blood pressure and that their myocardium operates with lower external mechanical efficiencies compared with those of smaller species. We discuss potential physiological and mechanical explanations, including the additional energy needed to support the arterial blood column above the heart in larger species, especially those with long necks, as well as the possible sources of greater internal energy losses from the heart of larger species. Thus, we present an updated view of how increasing blood pressure and decreasing efficiency of the myocardium result in an increasing fractional metabolic cost of perfusion as body size increases among resting mammals.
Speaking in Private: Privacy Expectations Depend on Communication Modality
Authors: Melzner Johann , Bonezzi Andrea , Meyvis Tom 
Published: October 2024

Consumers disclose personal information when they interact with connected technologies. The advent of voice technology has enabled consumers to interact with connected technologies not only through typing but also through speaking. The present research investigates whether consumers expect different levels of privacy for information they disclose via different communication modalities. The results of three studies suggest that consumers have more restrictive privacy expectations for information disclosed via speech as compared with text. The studies probe the viability of several mechanisms that may drive this effect and test practically relevant moderators. The results suggest that the effect is driven, at least in part, by increased feelings of ownership over content disclosed via speech as compared with text. Of relevance to multiple stakeholders, the article discusses implications for privacy regulation, privacy-preserving application design, targeted advertising, and the “privacy paradox.” This paper has been This paper was accepted by Catherine Tucker for the Special Issue on the Human-Algorithm Connection. Funding: This work was supported by Marketing Science Institute [4001309], NYU Stern Center for Global Economy and Business. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.03954 .
Production and Characterization of Cellulose Nanofibrils from Cotton Noil Waste
Authors: Ponnusamy Prabaharan Graceraj , Sharma Suraj , Mani Sudhagar 
Published: October 2024

HighlightsCotton noil is a waste short fiber from the cotton yarn industry.Cellulose nanofibrils were produced by ball-milling and high-pressure homogenization processes.The width of nanofibrils ranged from 50 to 70 nm, with about 80% crystallinity index.The 5% CNF had a tensile strength of about 25 MPa and can be used as a reinforcing material.Abstract. Cellulose nanofibrils (CNF), the nanostructured cellulose, are promising nanomaterials for bio-based barrier coating and packaging applications. In this study, we investigated the production of cellulose nanofibrils from cotton noil, a waste short-fiber from the cotton yarn industry. The cotton noil fibers were subjected to ball milling for 10 min and dispersed in water to prepare slurries with three different concentrations (1%, 5%, and 10% w/v). Then, the slurry was passed through a high-pressure homogenizer at 700 bar pressure for 14 cycles or until the fibers were fibrillated into CNF hydrogels. The CNF with 1% and 5% concentrations had an average width of 70 and 52 nm, respectively, while the 10% CNF concentration had a mix of both nanofibrils and microfibrils due to inconsistent fibrillation. Fourier Transform InfraRed (FTIR) spectroscopy and X-ray diffraction techniques on the isolated CNFs demonstrated that the manufacturing process did not affect the cellulose molecular structure or crystallinity. The tensile strength of CNF from 5% concentration was about 25 MPa. This simple manufacturing method can be applied to utilize cotton noil fibers to produce CNF for various applications. Keywords: Ball milling, Cellulose nanofibrils, Cotton noil, Homogenization, Tensile strength.