bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sarecycline pharmacokinetics/pharmacodynamics in the hollow-fibre model of Mycobacterium avium complex: so near and yet so far
Authors: Singh Sanjay , Boorgula Gunavanthi D , Aryal Santosh , Philley Julie V , Gumbo Tawanda , Srivastava Shashikant 
Published: November 2023

Abstract

Background
Poor sustained sputum culture conversion rates with the standard-of-care therapy highlight the need for better drugs to treat Mycobacterium avium complex pulmonary disease (MAC-PD).

Objective
To determine the pharmacokinetics/pharmacodynamics (PK/PD)-optimized exposure of sarecycline and its potential role in treating MAC-PD.

Methods
We performed MIC studies with MAC ATCC 700898 and 19 clinical isolates and test-tube static concentration–response studies. A dynamic hollow-fibre system model of intracellular MAC (HFS-MAC) study was performed mimicking six human-equivalent sarecycline dose concentration–time profiles to identify the PK/PD optimal exposure of sarecycline for MAC kill. The inhibitory sigmoid maximal effect (Emax) model was used for PK/PD analysis.

Results
The sarecycline MIC of MAC ATCC 700898 was 1 mg/L, while the MIC for the 19 clinical strains ranged between 32 and &gt;256 mg/L. The concentration mediating 50% of Emax (EC50) was similar between intracellular and extracellular MAC. In the HFS-MAC, all six sarecycline doses killed intracellular MAC, with an Emax of 1.0 log10 cfu/mL below Day 0 burden (stasis). The sarecycline EC80 (optimal) exposure was identified as AUC0–24/MIC = 139.46.

Conclusions
Sarecycline demonstrated anti-MAC Emax in the HFS-MAC model better than ethambutol but worse than omadacycline (&gt;5 log10 cfu/mL below stasis) in HFS-MAC. However, since currently approved highest oral sarecycline dose achieves an AUC0–24 of 48.2 mg·h/L and MAC MICs are &gt;32 mg/L, the target AUC0–24/MIC of 139.46 is unlikely to be achieved in patients.
Involvement of cardiac glycosides targeting Na/K-ATPase in their inhibitory effects on c-Myc expression via its transcription, translation and proteasomal degradation
Authors: Tokugawa Muneshige , Inoue Yasumichi , Aoki Hiromasa , Miyajima Chiharu , Ishiuchi Kan'ichiro , Tsurumi Kento , Kujirai Chisane , Morishita Daisuke , Matsuno Michiyo , Mizukami Hajime , Ri Masaki , Iida Shinsuke , Makino Toshiaki , Aoyama Mineyoshi , Hayashi Hidetoshi 
Published: November 2023

Abstract
Cardiac glycosides (CGs) have been used for decades to treat heart failure and arrhythmic diseases. Recent non-clinical and epidemiological findings have suggested that CGs exhibit anti-tumor activities. Therefore, CGs may be repositioned as drugs for the treatment of cancer. A detailed understanding of the anti-cancer mechanisms of CGs is essential for their application to the treatment of targetable cancer types. To elucidate the factors associated with the anti-tumor effects of CGs, we performed transcriptome profiling on human multiple myeloma AMO1 cells treated with periplocin, one of the CGs. Periplocin significantly down-regulated the transcription of MYC (c-Myc), a well-established oncogene. Periplocin also suppressed c-Myc expression at the protein levels. This repression of c-Myc was also observed in several cell lines. To identify target proteins for the inhibition of c-Myc, we generated CG-resistant (C9) cells using a sustained treatment with digoxin. We confirmed that C9 cells acquired resistance to the inhibition of c-Myc expression and cell proliferation by CGs. Moreover, the sequencing of genomic DNA in C9 cells revealed the mutation of D128N in α1-Na/K-ATPase, indicating the target protein. These results suggest that CGs suppress c-Myc expression in cancer cells via α1-Na/K-ATPase, which provides further support for the anti-tumor activities of CGs.
An oscillating magnetic field suppresses ice-crystal growth during rapid freezing of muscle tissue of mice
Authors: Okuda Kana , Kaori Kunitani , Kawauchi Aiko , Miyu Ishii , Yomogida Kentaro 
Published: November 2023

Abstract
Regenerative medicine would benefit from a safe and efficient cryopreservation method to prevent the structural disruption caused by ice-crystal formation in cells and tissue. Various attempts have been made to overcome this problem, one of which is the use of an oscillating magnetic field (OMF). However, the underlying mechanism is unclear. In this study, to evaluate the effect of an OMF on ice-crystal formation in the leg muscles of mice, we used to use the frozen-section method with a slower freezing rate than is, usual which resulted in ice crystals forming in the tissue. We assessed the mean size and number per unit area of intracellular ice holes in sections of muscle tissue, with and without OMF. Ice-crystal growth was reduced in frozen tissue subjected to OMF. Furthermore, we evaluated the structure and function of proteins in frozen tissue subjected to OMF by immunostaining using an anti-dystrophin antibody and by enzymatic histochemistry for NADH-TR and myosin ATPase. The results imply that the ability of OMF to suppress ice-crystal growth might be related to their stabilization of bound water in biomolecules during freezing.
The story of social media: evolving news coverage of social media in American politics, 2006–2021
Authors: Lane Daniel S , Overbye-Thompson Hannah , Gagrčin Emilija 
Published: November 2023

Abstract
This article examines how American news media have framed social media as political technologies over time. To do so, we analyzed 16 years of political news stories focusing on social media, published by American newspapers (N = 8,218) and broadcasters (N = 6,064) (2006–2021). Using automated content analysis, we found that coverage of social media in political news stories: (a) increasingly uses anxious, angry, and moral language, (b) is consistently focused on national politicians (vs. non-elite actors), and (c) increasingly emphasizes normatively negative uses (e.g., misinformation) and their remedies (i.e., regulation). In discussing these findings, we consider the ways that these prominent normative representations of social media may shape (and limit) their role in political life.
Too scared to share? Fear of social sanctions for political expression on social media
Authors: Weeks Brian E , Halversen Audrey , Neubaum German 
Published: November 2023

Abstract
While social media provide opportunities for political expression, many people may be reluctant to share their opinions if they fear personal or professional repercussions for posting political views. Fear of social sanctions (FOSSs) therefore represents a promising approach to investigate why people often avoid expressing political opinions online. Using panel survey data collected during the 2020 U.S. election, this study examines the predictors of FOSSs, as well as its relationship with several forms of online political expression. Results indicate that the ideological diversity of people’s online networks fosters their FOSSs, which in turn is associated with decreases in several types of online political expression. Thus, FOSSs may be an important determinant in individuals’ calculations to express political opinions online and may also hinder lower commitment forms of political engagement.
Inulin prebiotic ameliorates type 1 diabetes dictating regulatory T cell homing via CCR4 to pancreatic islets and butyrogenic gut microbiota in murine model
Authors: Guimarães Jhefferson Barbosa , Rodrigues Vanessa Fernandes , Pereira Ítalo Sousa , Manso Gabriel Martins da Costa , Elias-Oliveira Jefferson , Leite Jefferson Antônio , Waldetario Mariana Camila Gonçalves Miranda , de Oliveira Sarah , Gomes Arilson Bernardo dos Santos Pereira , Faria Ana Maria Caetano , Ramos Simone Gusmão , Bonato Vânia L D , Silva João Santana , Vinolo Marco Aurélio Ramirez , Sampaio Ulliana Marques , Clerici Maria Teresa Pedrosa Silva , Carlos Daniela 
Published: November 2023

Abstract
Gut dysbiosis is linked to type 1 diabetes mellitus (T1D). Inulin (INU), a prebiotic, modulates the gut microbiota, promoting beneficial bacteria that produce essential short-chain fatty acids for immune regulation. However, how INU affects T1D remains uncertain. Using a streptozotocin-induced (STZ) mouse model, we studied INU's protective effects. Remarkably, STZ + INU mice resisted T1D, with none developing the disease. They had lower blood glucose, reduced pancreatic inflammation, and normalized serum insulin compared with STZ + SD mice. STZ + INU mice also had enhanced mucus production, abundant Bifidobacterium, Clostridium cluster IV, Akkermansia muciniphila, and increased fecal butyrate. In cecal lymph nodes, we observed fewer CD4+Foxp3+ regulatory T cells expressing CCR4 and more Foxp3+CCR4+ cells in pancreatic islets, with higher CCL17 expression. This phenotype was absent in CCR4-deficient mice on INU. INU supplementation effectively protects against experimental T1D by recruiting CCR4+ regulatory T cells via CCL17 into the pancreas and altering the butyrate-producing microbiota.
Contribution of smoking, disease history, and survival to lung cancer disparities in Black individuals
Authors: Skolnick Sarah , Cao Pianpian , Jeon Jihyoun , Meza Rafael 
Published: November 2023

Abstract

Background
Lung cancer is the leading cause of cancer deaths and disproportionately affects self-identified Black or African American (“Black”) people, especially considering their relatively low self-reported smoking intensity rates. This study aimed to determine the relative impact of smoking history and lung cancer incidence risk, histology, stage, and survival on these disparities.

Methods
We used 2 lung cancer models (MichiganLung-All Races and MichiganLung-Black) to understand why Black people have higher rates of lung cancer deaths. We studied how different factors, such as smoking behaviors, cancer development, histology, stage at diagnosis, and lung cancer survival, contribute to these differences.

Results
Adjusted for smoking history, approximately 90% of the difference in lung cancer deaths between the overall and Black populations (born in 1960) was the result of differences in the risk of getting lung cancer. Differences in the histology and stage of lung cancer and survival had a small impact (4% to 6% for each). Similar results were observed for the 1950 and 1970 birth cohorts, regardless of their differences in smoking patterns from the 1960 cohort.

Conclusions
After taking smoking into account, the higher rate of lung cancer deaths in Black people can mostly be explained by differences in the risk of developing lung cancer. As lung cancer treatments and detection improve, however, other factors may become more important in determining differences in lung cancer mortality between the Black and overall populations. To prevent current disparities from becoming worse, it is important to make sure that these improvements are available to everyone in an equitable way.
Self-Control in Pediatric Migraine Management: A Topical Review
Authors: Conour Cecily N , Sugiwaka Hiroko , Nelson Cecelia I , Duncan Christina L 
Published: November 2023

Abstract

Objective
This review examines the role that two types of self-control may play in youth’s self-management of migraine. Although traditionally conceptualized from an inhibitory lens, self-control has both initiatory and inhibitory functions, and the authors suggest the distinction is important in relation to youth’s ability to adhere to different components of migraine treatment regimens.

Methods
A topical review of the literature was conducted to identify evidence-based interventions to treat pediatric migraine and conceptualize the role self-control (both initiatory and inhibitory) may play in adherence to its regimen. Both PsycInfo and PubMed databases were used to identify relevant articles.

Results
Existing evidence-based interventions and recommendations for pediatric migraine require inhibitory self-control (e.g., avoiding caffeine, tobacco) and initiatory self-control (e.g., taking medication). Formal intervention programs (e.g., cognitive behavioral therapy) tend to employ initiatory self-control (e.g., modifying physical reactions in response to biofeedback).

Conclusions
Understanding the distinct types of self-control required for adherence to different interventions allows for a better conceptualization of self-management of pediatric migraine. Individuals may struggle with adherence when they have deficits in one or both types of self-control skills. Future research should consider whether self-control is associated with differential adherence patterns in pediatric migraine management.
Bayesian profile regression for clustering analysis involving a longitudinal response and explanatory variables
Authors: Rouanet Anaïs , Johnson Rob , Strauss Magdalena , Richardson Sylvia , Tom Brian D , White Simon R , Kirk Paul D W 
Published: November 2023

Abstract
The identification of sets of co-regulated genes that share a common function is a key question of modern genomics. Bayesian profile regression is a semi-supervised mixture modelling approach that makes use of a response to guide inference toward relevant clusterings. Previous applications of profile regression have considered univariate continuous, categorical, and count outcomes. In this work, we extend Bayesian profile regression to cases where the outcome is longitudinal (or multivariate continuous) and provide PReMiuMlongi, an updated version of PReMiuM, the R package for profile regression. We consider multivariate normal and Gaussian process regression response models and provide proof of principle applications to four simulation studies. The model is applied on budding-yeast data to identify groups of genes co-regulated during the Saccharomyces cerevisiae cell cycle. We identify four distinct groups of genes associated with specific patterns of gene expression trajectories, along with the bound transcriptional factors, likely involved in their co-regulation process.
Reducing PHYTOENE SYNTHASE activity fine-tunes the abundance of a cis-carotene-derived signal that regulates the PIF3/HY5 module and plastid biogenesis
Authors: Hou Xin , Alagoz Yagiz , Welsch Ralf , Mortimer Matthew D , Pogson Barry J , Cazzonelli Christopher I 
Published: November 2023

Abstract
PHYTOENE SYNTHASE (PSY) is a rate-limiting enzyme catalysing the first committed step of carotenoid biosynthesis, and changes in PSY gene expression and/or protein activity alter carotenoid composition and plastid differentiation in plants. Four genetic variants of PSY (psy-4, psy-90, psy-130, and psy-145) were identified using a forward genetics approach that rescued leaf virescence phenotypes and plastid abnormalities displayed by the Arabidopsis CAROTENOID ISOMERASE (CRTISO) mutant ccr2 (carotenoid and chloroplast regulation 2) when grown under a shorter photoperiod. The four non-lethal mutations affected alternative splicing, enzyme–substrate interactions, and PSY:ORANGE multi-enzyme complex binding, constituting the dynamic post-transcriptional fine-tuning of PSY levels and activity without changing localization to the stroma and protothylakoid membranes. psy genetic variants did not alter total xanthophyll or β-carotene accumulation in ccr2, yet they reduced specific acyclic linear cis-carotenes linked to the biosynthesis of a currently unidentified apocarotenoid signal regulating plastid biogenesis, chlorophyll biosynthesis, and photomorphogenic regulation. ccr2 psy variants modulated the PHYTOCHROME-INTERACTING FACTOR 3/ELONGATED HYPOCOTYL 5 (PIF3/HY5) ratio, and displayed a normal prolamellar body formation in etioplasts and chlorophyll accumulation during seedling photomorphogenesis. Thus, suppressing PSY activity and impairing PSY:ORANGE protein interactions revealed how cis-carotene abundance can be fine-tuned through holoenzyme–metabolon interactions to control plastid development.
Imaging Threading Dislocations and Surface Steps in Nitride Thin Films Using Electron Backscatter Diffraction
Authors: Hiller Kieran P , Winkelmann Aimo , Hourahine Ben , Starosta Bohdan , Alasmari Aeshah , Feng Peng , Wang Tao , Parbrook Peter J , Zubialevich Vitaly Z , Hagedorn Sylvia , Walde Sebastian , Weyers Markus , Coulon Pierre-Marie , Shields Philip A , Bruckbauer Jochen , Trager-Cowan Carol 
Published: November 2023

Abstract
Extended defects, like threading dislocations, are detrimental to the performance of optoelectronic devices. In the scanning electron microscope, dislocations are traditionally imaged using diodes to monitor changes in backscattered electron intensity as the electron beam is scanned over the sample, with the sample positioned so the electron beam is at, or close to the Bragg angle for a crystal plane/planes. Here, we use a pixelated detector instead of single diodes, specifically an electron backscatter diffraction (EBSD) detector. We present postprocessing techniques to extract images of dislocations and surface steps, for a nitride thin film, from measurements of backscattered electron intensities and intensity distributions in unprocessed EBSD patterns. In virtual diode (VD) imaging, the backscattered electron intensity is monitored for a selected segment of the unprocessed EBSD patterns. In center of mass (COM) imaging, the position of the center of the backscattered electron intensity distribution is monitored. Additionally, both methods can be combined (VDCOM). Using both VD and VDCOM, images of only threading dislocations, or dislocations and surface steps can be produced, with VDCOM images exhibiting better signal-to-noise. The applicability of VDCOM imaging is demonstrated across a range of nitride semiconductor thin films, with varying surface step and dislocation densities.
Antibacterial Efficacy of a Chitosan-Based Hydrogel Modified With Epsilon-Poly-l-Lysine Against Pseudomonas aeruginosa in a Murine-Infected Burn Wound Model
Authors: Moon Andrea Y , Bailey Emily J , Polanco Jonilee A , Kurata Wendy E , Pierce Lisa M 
Published: November 2023

ABSTRACT

Introduction
Because antibiotic resistance is increasing worldwide and the leading cause of death in burn patients is an infection, an urgent need exists for nonantibiotic approaches to eliminate multidrug-resistant bacteria from burns to prevent their systemic dissemination and sepsis. We previously demonstrated the significant antibiofilm activity of a chitosan (CS) hydrogel containing the antimicrobial peptide epsilon-poly-l-lysine (EPL) against multidrug-resistant Pseudomonas aeruginosa using ex vivo porcine skin. In this study, we evaluated the in vivo antibacterial efficacy of a CS/EPL hydrogel against P. aeruginosa in a murine burn wound infection model.

Materials and Methods
Full-thickness burns were created on the dorsum using a heated brass rod and were inoculated with bioluminescent, biofilm-forming P. aeruginosa (Xen41). Mice were treated with CS/EPL, CS, or no hydrogel applied topically 2 or 24 hours after inoculation to assess the ability to prevent or eradicate existing biofilms, respectively. Dressing changes occurred daily for 3 days, and in vivo bioluminescence imaging was performed to detect and quantitate bacterial growth. Blood samples were cultured to determine systemic infection. In vitro antibacterial activity and cytotoxicity against human primary dermal fibroblasts, keratinocytes, and mesenchymal stem cells were also assessed.

Results
CS/EPL treatment initiated at early or delayed time points showed a significant reduction in bioluminescence imaging signal compared to CS on days 2 and 3 of treatment. Mice administered CS/EPL had fewer bloodstream infections, lower weight loss, and greater activity than the untreated and CS groups. CS/EPL reduced bacterial burden by two orders of magnitude in vitro and exhibited low cytotoxicity against human cells.

Conclusion
A topical hydrogel delivering the antimicrobial peptide EPL demonstrates in vivo efficacy to reduce but not eradicate established P. aeruginosa biofilms in infected burn wounds. This biocompatible hydrogel shows promise as an antimicrobial barrier dressing for the sustained protection of burn wounds from external bacterial contamination.
Early Enteral Nutrition in Aeromedically Evacuated Critically Ill/Injured Patients With a Resultant Validation Algorithm for the Theater Validating Flight Surgeon
Authors: Butler William P , Woody Sarah K , Huffman Sarah L , Harding Charles J , Brown Kayla N , Smith Danny E , Noe Todd C , Gholson Andre D 
Published: November 2023

ABSTRACT

Introduction
Early enteral feeding in critically ill/injured patients promotes gut integrity and immunocompetence and reduces infections and intensive care unit/hospital stays. Aeromedical evacuation (AE) often takes place concurrently. As a result, AE and early enteral feeding should be inseparable.

Materials and Methods
This retrospective descriptive study employed AE enteral nutrition (EN) data (2007–2019) collected from patients who were U.S. citizens and mechanically ventilated. The dataset was created from the En Route Critical Care, Transportation Command Regulating and Command and Control Evacuation System, and Theater Medical Data Store databases. Comparisons were performed between patients extracted and patients not extracted, patients treated with EN and patients treated without EN, and within the EN group, between AE Fed and AE Withheld. The impact of the nutrition support in the Joint Trauma System Clinical Practice Guidelines (CPG) was assessed using the ‘before’ and ‘after’ methodology.

Results
An uptick in feeding rates was found after the 2010 CPG, 15% → 17%. With the next two CPG iterations, rates rose significantly, 17% → 48%. Concurrently, AE feeding holds rose significantly, 10% → 24%, later dropping to 17%. In addition, little difference was found between those patients not enterally fed preflight and those enterally fed across collected demographic, mission, and clinical parameters. Likewise, no difference was found between those enterally fed during AE and those withheld. Yet, 83% of the study’s patients were not fed, and 18% of those that were fed had feeding withheld for AE.

Conclusions
It appeared that the Clinical Practice Guidelines (CPGs) reinforced the value of feeding, but may well have sensitized to the threat of aspiration. It also appeared that early enteral feeding was underprescribed and AE feeding withholds were overprescribed. Consequently, an algorithm was devised for the Theater Validating Flight Surgeon, bearing in mind relevant preflight/inflight/clinical issues, with prescriptions designed to boost feeding, diminish AE withholding, and minimize complications.