bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling the cost-effectiveness of TasP and PrEP in female sex workers in Cotonou, Benin
Authors: Cianci F , Geidelberg L , Mitchell KM , Kessou L , Mboup A , Diabate S , Behanzin L , Guedou FA , Zannou DM , Geraldo N , Goma-Matsétsé E , Giguère K , Aza-Gnandji M , Diallo M , Kêkê R , Bachabi M , Dramane K , Lafrance C , Affolabi D , Gagnon MP , Gangbo F , Silhol R , Terris-Prestholt F , Boily MC , Alary M , Vickerman P 
Published: December 2023

AbstractIntroductionTreatment as prevention (TasP) and pre-exposure prophylaxis (PrEP) could impact the HIV epidemic among Female Sex Workers (FSW) but their cost-effectiveness is uncertain in this group. This study aims to model the cost-effectiveness of TasP and PrEP among FSW in Cotonou, Benin.MethodsA demonstration study assessed TasP and PrEP use among FSW in Cotonou. A dynamic HIV transmission model was developed to estimate the impact of this intervention and published elsewhere. Incremental economic costs of the study were collected prospectively capturing both provider and FSW costs. The incremental cost-effectiveness ratio per HIV infection and disability-adjusted life years (DALY) averted were estimated over a 20 year time horizon with costs converted to USD 2020 and both costs and DALYs discounted at 4.5% per year. Different cost scenarios were modelled to investigate the cost-effectiveness of the intervention as delivered by the government reflecting current day implementation and resource costs.ResultsThe mean provider annual economic cost per FSW on TasP was $646, with an initiation cost of $347 and mean annual user costs were $16. The mean initiation costs for PrEP were $268, mean annual provider costs were $359-$499 and annual user cost $15-$21 depending on adherence level. TasP was found to be cost saving for all cost scenarios examined compared to routine HIV care for FSW. PrEP was not cost-effective for any cost scenario, population coverage or adherence level examined.ConclusionOur results support TasP but not PrEP for FSW in our setting. A streamlined, outreach delivery model with reduced costs should be investigated to assess its cost-effectiveness in this setting.
Analysis of Engagement withCuidaTEXT, a Text Message Intervention for Dementia Caregiver Support among Latinos
Authors: Medina Valerie , Watts Amber , Fracachán-Cabrera Monica , Hazlewood Cameo , Ramirez-Mantilla Mariana , Vidoni Eric D. , Perales-Puchalt Jaime 
Published: December 2023

AbstractObjectivesTo assess the impact of a text message intervention,CuidaTEXT, on participant engagement and its subsequent associations with socio-demographic factors, acceptability measures, and clinical outcomes among Latino dementia caregivers.MethodsCuidaTEXTis a six-month, bilingual, and bidirectional intervention. We enrolled 24 Latino caregivers in a one-arm feasibility trial. Participants received approximately one automatic daily text message and could engage with the intervention by texting specific keywords (e.g., STRESS to receive messages about stress-coping), and by chat-texting with a live coach. We used metrics and psychometric scales to quantify variables.ResultsParticipants sent a total of 1,847 messages toCuidaTEXT. Higher engagement was associated with higher intervention satisfaction (r=0.6, p=0.007), as were several other acceptability outcomes. We found no associations between engagement withCuidaTEXTand sociodemographic or clinical outcomes (p>0.05).ConclusionEncouraging interaction withCuidaTEXTmight lead to higher levels of satisfaction with the intervention. However, it might be that those who are highly satisfied, engage more withCuidaTEXT. Future research should determine the directionality of these associations.Clinical ImplicationsIncreasing opportunities to engage in text messaging may increase Latino caregivers’ satisfaction with caregiver support interventions.
Early-stage idiopathic pulmonary fibrosis is characterized by bronchoalveolar accumulation of SPP1+macrophages
Authors: Yu Jiangyan , Thomas Jake , Haub Jessica , Pizarro Carmen , Zhang Miaomiao , Biener Leonie , Becker Matthias , Zhang Lili , Kapellos Theodore S. , Schulte Wolfgang , Schultze Joachim L. , Hasenauer Jan , Skowasch Dirk , Schlitzer Andreas 
Published: December 2023

AbstractPatients affected by idiopathic pulmonary fibrosis (IPF), a progressive chronic and eventually fatal lung disease with unknown cause, suffer from delayed diagnosis and limited personalized treatment options due to the lack of predictive and staging relevant disease markers. Prior studies focused on the cellular and transcriptomic changes found in lung tissue during terminal IPF-associated lung fibrosis. In clinical routine, bronchoscopy is applied for diagnosis and staging of suspected IPF affected individuals, thus providing us with a clinically applicable window, to study the cellular and transcriptional changes within affected individuals at the time of diagnosis. Here we study a cohort consisting of 11 IPF affected individuals and 11 healthy controls. We investigate their single cell transcriptomic profile alongside the surface phenotype of alveolar-resident immune cells. Single cell transcriptional analysis reveals accumulation of SPP1+macrophages (SPP1+Mφ) within the alveolar space during early stage diagnosed IPF, in the absence of a decline in lung function. SPP1+Mφ were characterized by high expression of lipid storage and handling genes, accumulation of intracellular cholesterol and expression of proinflammatory cytokine expression.In silicodevelopmental trajectory analysis revealed that SPP1+Mφ are likely derived from classical monocytes. Finally, to confirm the clinical diagnostic value of SPP1+Mφ, we developed a flow cytometry panel to rapidly identify and test for the presence of SPP1+Mφ in bronchoalveolar lavage samples. The new panel has confirmed the increased frequency of SPP1+Mφ in early-IPF in an independent validation cohort. Taken together, we show that SPP1+Mφ are associated with early IPF pathogenesis in the absence of a decline in lung function, thus providing a clinically valuable markers for diagnosis of early IPF in clinical practice.HighlightsIPF patients can be stratified into early and advanced disease groups based on clinical features.Single cell transcriptomic and high dimensional flow cytometry enabled mapping of the myeloid compartment across the continuum of idiopathic pulmonary fibrosis associated disease states.SPP1+Mφ accumulated during early clinical stage of IPF.Development of a clinically applicable SPP1⁺Mφ identification panel.
AKAP150-anchored PKA regulation of synaptic transmission and plasticity, neuronal excitability and CRF neuromodulation in the lateral habenula
Authors: Simmons S.C. , Flerlage W.J. , Langlois L.D. , Shepard R.D. , Bouslog C. , Thomas E.H. , Gouty K.M. , Sanderson J.L. , Gouty S. , Cox B.M. , Dell’Acqua M.L. , Nugent F.S. 
Published: December 2023

AbstractNumerous studies of hippocampal synaptic function in learning and memory have established the functional significance of the scaffolding A-kinase anchoring protein 150 (AKAP150) in kinase and phosphatase regulation of synaptic receptor and ion channel trafficking/function and hence synaptic transmission/plasticity, and neuronal excitability. Emerging evidence also suggests that AKAP150 signaling may play a critical role in brain’s processing of rewarding/aversive experiences. Here we focused on an unexplored role of AKAP150 in the lateral habenula (LHb), a diencephalic brain region that integrates and relays negative reward signals from forebrain striatal and limbic structures to midbrain monoaminergic centers. LHb aberrant activity (specifically hyperactivity) is also linked to depression. Using whole cell patch clamp recordings in LHb of male wildtype (WT) and ΔPKA knockin mice (with deficiency in AKAP-anchoring of PKA), we found that the genetic disruption of PKA anchoring to AKAP150 significantly reduced AMPA receptor (AMPAR)-mediated glutamatergic transmission and prevented the induction of presynaptic endocannabinoid (eCB)-mediated long-term depression (LTD) in LHb neurons. Moreover, ΔPKA mutation potentiated GABAAreceptor (GABAAR)-mediated inhibitory transmission postsynaptically while increasing LHb intrinsic neuronal excitability through suppression of medium afterhyperpolarizations (mAHPs). Given that LHb is a highly stress-responsive brain region, we further tested the effects of corticotropin releasing factor (CRF) stress neuromodulator on synaptic transmission and intrinsic excitability of LHb neurons in WT and ΔPKA mice. As in our earlier study in rat LHb, CRF significantly suppressed GABAergic transmission onto LHb neurons and increased intrinsic excitability by diminishing small-conductance potassium (SK) channel-mediated mAHPs. ΔPKA mutation-induced suppression of mAHPs also blunted the synaptic and neuroexcitatory actions of CRF in mouse LHb. Altogether, our data suggest that AKAP150 complex signaling plays a critical role in regulation of AMPAR and GABAAR synaptic strength, glutamatergic plasticity and CRF neuromodulation possibly through AMPAR and potassium channel trafficking and eCB signaling within the LHb.
Comprehensive chromatome profiling identifies metabolic enzymes on chromatin in healthy and cancer cells
Authors: Kourtis S , Guirola M , Pardo-Lorente N , Ghose R , Garcia-Cao M , Gañez-Zapater A , Haynes S , Fontaine F , Muller A , Sdelci S 
Published: December 2023

AbstractMetabolic and epigenetic rewiring are widely considered hallmarks of cancer, with emerging evidence of crosstalk between them. Anecdotal evidence of metabolic enzymes moonlighting in the chromatin environment has suggested how this crosstalk might be facilitated, but the extent of nuclear relocalization of metabolic enzymes remains elusive. Here, we provide a comprehensive chromatin proteomics resource across cancer lineages as well as healthy samples and demonstrate that metabolic enzyme moonlighting on chromatin is widespread across tissues and pathways. We show that the abundance of metabolic enzymes on chromatin is tissue-specific, with oxidative phosphorylation proteins depleted in lung cancer samples, perhaps suggesting an interplay between cell identity and nuclear metabolism. Finally, we explore metabolic functions in the chromatin environment and show that one-carbon folate enzymes are associated with DNA damage and repair processes, providing an approach to explore non-canonical functions of metabolic enzymes.
4D bioprinted self-folding scaffolds enhance cartilage formation in the engineering of trachea
Authors: Chiesa Irene , Esposito Alessio , Vozzi Giovanni , Gottardi Riccardo , De Maria Carmelo 
Published: December 2023

AbstractTrachea defects that required surgical interventions are increasing in number in the recent years, especially for pediatric patients. However, current gold standards, such as biological grafts and synthetic prothesis, do not represent an effective solution, due to the lack of mimicry and regeneration capability. Bioprinting is a cutting-edge approach for the fabrication of biomimetic scaffold to empower tissue engineering toward trachea replacement. In this study, we developed a self-folding gelatin-based bilayer scaffold for trachea engineering, exploiting the 4D bioprinting approach, namely the fabrication of dynamic scaffolds, able to shape morph in a predefined way after the application of an environmental stimulus. Indeed, starting form a 2D flat position, upon hydration, this scaffold forms a closed tubular structure. An analytical model, based on Timoshenko’s beam thermostats, was developed, and validated to predict the radius of curvature of the scaffold according to the material properties and the scaffold geometry. The 4D bioprinted structure was tested with airway fibroblast, lung endothelial cells and ear chondral progenitor cells (eCPCs) toward the development of a tissue engineered trachea. Cells were seeded on the scaffold in its initial flat position, maintained their position after the scaffold actuation and proliferated over or inside it. The ability of eCPCs to differentiate towards mature cartialge was evaluated. Interestingly, real-time PCR revealed that differentiating eCPCs on the 4D bioprinted scaffold promote healthy cartilage formation, if compared with eCPCs cultured on 2D static scaffold. Thus, eCPCs can perceive scaffold folding and its final curvature and to react to it, towards the formation of mature cartilage for the airway.
A novel method of testing the antimicrobial potentials ofExiguobacterium aurantiacum, Lysinibacillus boronitoleransandBacillus megaterium
Authors: Jain Radhika , Belwalkar Mugdha , Shukla Varsha , Lokur Anushree , Rege Mayuri 
Published: December 2023

AbstractMicroorganisms can be an effective source for antimicrobial compounds including peptides that provide an evolutionary advantage to them in specific niches. Prior studies have noted the antimicrobial properties ofExiguobacterium aurantiacum, Lysinibacillus boronitoleransandBacillus megateriumbut they used time- and resource-intensive procedures to prepare the extracts (2, 10). We wanted to explore a more cost-effective, time-effective and simpler method of testing the antimicrobial potential of bacterial extracts. Our extraction protocol is a one-step incubation of the organism in the solvent overnight, followed by a standard well diffusion based assay to test its antimicrobial effect. We tested this method with three cultures isolated from the premises of Mumbai railway stations:E. aurantiacum, L. boronitoleransandBacillus megaterium. These extracts were tested against human pathogensStaphylococcus aureusandEnterococcus faecalis. E. aurantiacum, L. boronitoleransandB. megateriuminhibitedS. aureusby 9.17 ± 0.42, 9.25 ± 0.48 and 10.50 ± 1.5 mm, respectively, andE. faecalisby 15.79 ± 2.25, 14.21 ± 0.88 and 17.5 ± 2.89 mm, respectively. This approach is therefore suggested to be effective for screening the antimicrobial activity of these bacteria.
Pan-cancer analysis of pyrimidine metabolism reveals signaling pathways connections with chemoresistance role
Authors: Ramesh Vignesh , Demirdizen Mert , Pinna Luisa , Doktor Thomas Koed , Siddiqui Mohammad Aarif , Ceppi Paolo 
Published: December 2023

AbstractDeregulated nucleotide metabolism, and in particular increased pyrimidine metabolism (PyMet), has been shown to contribute to various pathological features of cancer including chemoresistance and epithelial-to-mesenchymal transition. However, cancer often encompasses complex signaling and metabolic pathway cascades for its progression, and understanding of these molecular regulatory processes in pyrimidine metabolism is quite limited. Therefore, a comprehensive pan-cancer analysis in around 10,000 gene expression profiles of 32 cancer types was employed using a pathway-based approach utilizing gene-sets representing various signaling and metabolic pathways. The analysis identified several top connections with PyMet including TERT, MTOR, DAX1, HOXA1, TP53 and TNC implying an inter-dependency of regulations which in turn was linked to the chemoresistance mechanisms. PyMet-signaling interactions were validated within vitroderived gene-sets from endogenous thymidylate synthase (TYMS)-promoter activity reporter, fromTYMSknockdown and from brequinar treatment, and further at single cell transcriptome level. Strikingly, brequinar treatment profile showed a strong inverse association pattern with doxorubicin chemoresistance in multiple cancer types. The study highlights the PyMet-pathway interactions and its role in chemoresistance, thereby providing an effective tool for improving PyMet targeting strategy in cancer. The analysis as an accessible resource is available at:www.pype.compbio.sdu.dkHighlightsPan-cancer analysis showed pyrimidine metabolism connections with signaling pathways Top pathway interactors of pyrimidine metabolism were TERT, HOXA1, TP53 and TNC In vitro derived pyrimidine gene-sets recapitulate cancer patients’ pathway analysis Pyrimidine associated pathways confer chemoresistance in multiple cancer types Pyrimidine metabolic inhibitor brequinar reversed doxorubicin chemoresistance feature
Adaptable Fabrication of Vascularized Milliscale Tissues in Membrane-Free Organ Chips Manufactured with 3D Printed Molds
Authors: Byrne C. Ethan , Conrad K. Michael , Martier Ashley T. , Fortes Gabrielle , Kpeli G. Wills , Olsen Elisabet , Bralower William , Culp Caroline C. , Wendell Max , Boone Keefer A. , Mondrinos Mark J. 
Published: December 2023

ABSTRACTInexpensive stereolithography (SLA) 3D printing enables rapid prototyping of resin molds for polydimethylsiloxane (PDMS) soft lithography and organ chip fabrication, but geometric distortion and surface roughness of SLA resins can impede the development of adaptable manufacturing workflows. This study reports post-processing procedures for manufacturing SLA-printed molds built with a Formlabs F3 printer that produce fully cured, flat, patently bonded, and optically clear PDMS organ chips. User injection loading tests with iterated guide structure designs were conducted to achieve engineering reduction to practice of milliscale membrane-free organ chips (MFOC), defined as reproducible loading of aqueous solutions without failure of surface tension-based liquid patterning. The optimized manufacturing workflow was applied to further engineer milliscale MFOC for specific applications in modeling vascular physiology and pathobiology. The open lateral interfaces of bulk tissues seeded in MFOC facilitate the formation of anastomoses with internal vasculature to create milliscale perfusable vascular beds. After optimizing bulk tissue vasculogenesis in MFOC, we developed a method for seeding the bulk tissue interfaces with a confluent endothelium to stimulate self-assembly of perfusable anastomoses with the internal vasculature. Rocker- and pump-based flow-conditioning protocols were tested to engineer enhanced barrier function of the perfusable internal vasculature. Modularity of the MFOC design enabled creation of a multi-organ device that was used to model decaying gradients of cancer-associated vascular inflammation in organ compartments positioned at increasing distances from a tumor compartment. These easily adaptable methods for designing and fabricating vascularized microphysiological systems can accelerate their adoption in a diverse range of preclinical laboratory settings.
Segmentation of supragranular and infragranular layers in ultra-high resolution 7Tex vivoMRI of the human cerebral cortex
Authors: Zeng Xiangrui , Puonti Oula , Sayeed Areej , Herisse Rogeny , Mora Jocelyn , Evancic Kathryn , Varadarajan Divya , Balbastre Yael , Costantini Irene , Scardigli Marina , Ramazzotti Josephine , DiMeo Danila , Mazzamuto Giacomo , Pesce Luca , Brady Niamh , Cheli Franco , Pavone Francesco Saverio , Hof Patrick R. , Frost Robert , Augustinack Jean , van der Kouwe Andŕe , Iglesias Juan Eugenio , Fischl Bruce 
Published: December 2023

AbstractAccurate labeling of specific layers in the human cerebral cortex is crucial for advancing our understanding of neurodevelopmental and neurodegenerative disorders. Lever-aging recent advancements in ultra-high resolutionex vivoMRI, we present a novel semi-supervised segmentation model capable of identifying supragranular and infragranular layers inex vivoMRI with unprecedented precision. On a dataset consisting of 17 whole-hemisphereex vivoscans at 120µm, we propose a multi-resolution U-Nets framework (MUS) that integrates global and local structural information, achieving reliable segmentation maps of the entire hemisphere, with Dice scores over 0.8 for supra- and infragranular layers. This enables surface modeling, atlas construction, anomaly detection in disease states, and cross-modality validation, while also paving the way for finer layer segmentation. Our approach offers a powerful tool for comprehensive neuroanatomical investigations and holds promise for advancing our mechanistic understanding of progression of neurodegenerative diseases.
Imaging the dynamics of uterine contractions in early pregnancy
Authors: Dawson Madeline , Flores Diana , Zou Lisa , Anandasenthil Shivani , Mahesh Rohit , Zavala Olmo , Arora Ripla 
Published: December 2023

ABSTRACTThe myometrium or smooth muscle of the uterus contracts throughout the life of the organ. Uterine muscle contractility is essential for reproductive processes including sperm and embryo transport, and during the uterine cycle to remove menstrual effluent or estrus debris. Even still, uterine contractions have primarily only been studied in the context of preterm labor. This is partly due to a lack of methods for studying the contractile characteristics of the uterine muscle in the intact organ. Here, we describe an imaging-based method to evaluate the contractility of both the longitudinal and circular muscles of the uterus in the cycling stages and in early pregnancy. By transforming the image-based data into 3D spatiotemporal contractility maps, we calculate waveform characteristics of muscle contractions, including amplitude, frequency, wavelength, and velocity. We report that the native organ is highly contractile during the progesterone-dominant diestrus stage of the cycle when compared to the estrogen-dominant proestrus and estrus stages. We also observed correlations between contractility during pre-implantation stages of pregnancy and observed embryo movement patterns. During the first phase of embryo movement when clustered embryos move towards the middle of the uterine horn, uterine contractions are dynamic and non-uniform between different segments of the uterine horn. In the second phase of embryo movement, contractions are more uniform and rhythmic throughout the uterine horn. Finally, when our method is applied toLpar3mutant uteri that display faster embryo movement, we observe global and regional increases in contractility. Our method provides a means to understand the wave characteristics of uterine smooth muscle in response to modulators and in genetic mutants. Better understanding uterine contractility in the early pregnancy stages is critical for the advancement of artificial reproductive technologies and a possibility of modulating embryo movement during clinical embryo transfers.