bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Contrast Enhanced MRI Mapping of Vascular Permeability for Evaluation of Breast Cancer Neoadjuvant Chemotherapy Response Using Image-to-Image Conditional Generative Adversarial Networks
Authors: Arledge Chad A. , Zhao Alan H. , Topaloglu Umit , Zhao Dawen 
Published: September 2024

AbstractDynamic contrast enhanced (DCE) MRI is a non-invasive imaging technique that has become a quantitative standard for assessing tumor microvascular permeability. Through the application of a pharmacokinetic (PK) model to a series of T1-weighed MR images acquired after an injection of a contrast agent, several vascular permeability parameters can be quantitatively estimated. These parameters, including Ktrans, a measure of capillary permeability, have been widely implemented for assessing tumor vascular function as well as tumor therapeutic response. However, conventional PK modeling for translation of DCE MRI to PK vascular permeability parameter maps is complex and time-consuming for dynamic scans with thousands of pixels per image. In recent years, image-to-image conditional generative adversarial network (cGAN) is emerging as a robust approach in computer vision for complex cross-domain translation tasks. Through a sophisticated adversarial training process between two neural networks, image-to-image cGANs learn to effectively translate images from one domain to another, producing images that are indistinguishable from those in the target domain. In the present study, we have developed a novel image-to-image cGAN approach for mapping DCE MRI data to PK vascular permeability parameter maps. The DCE-to-PK cGAN not only generates high-quality parameter maps that closely resemble the ground truth, but also significantly reduces computation time over 1000-fold. The utility of the cGAN approach to map vascular permeability is validated using open-source breast cancer patient DCE MRI data provided by The Cancer Imaging Archive (TCIA). This data collection includes images and pathological analyses of breast cancer patients acquired before and after the first cycle of neoadjuvant chemotherapy (NACT). Importantly, in good agreement with previous studies leveraging this dataset, the percentage change of vascular permeability Ktransderived from the DCE-to-PK cGAN enables early prediction of responders to NACT.
Changes in the prevalence of the common risk factors for non-communicable diseases in Uganda between 2014 and 2023: Informed by nationally representative cross-sectional surveys
Authors: Kusolo Ronald , Mutungi Gerald , Mbuliro Mary , Kajjura Richard , Wesonga Ronald , Bahendeka Silver K. , Guwatudde David 
Published: September 2024

ABSTRACTBackgroundNon-communicable diseases (NCDs) remain the biggest contributor to global mortality. Although communicable diseases still contribute highest to mortality in the African region, the proportion contributed by NCDs continues to rise. An important way to control NCDs is to focus on reducing the prevalence of the common NCD risk factors. As such, monitoring changes in the prevalence of these risk factors is essential for better NCD prevention planning. Uganda conducted its first nationally representative NCD risk factor survey in 2014, and a second in 2023. We analyzed the prevalence of the common NCD risk factors using data from the two surveys to identify which risk factors changed between 2014 and 2023.MethodsBoth surveys drew countrywide samples stratified by the four regions of the country, and by rural-urban locations. The World Health Organization’s STEPs tool was used to collect data on demographic and behavioral characteristics, and physical and biochemical measurements. We defined and calculated weighted prevalence of the following common NCD risk factors: high blood pressure, high blood glucose, overweight and obesity, current use of alcohol, current tobacco use, inadequate consumption of fruits and vegetables, inadequate physical activity, and sedentariness.ResultsThe 2014 survey enrolled a total of 3906 participants, whereas that of 2023 enrolled 3694 participants. The NCD risk factor prevalences that increased significantly were: high blood glucose from 1.3% in 2014, to 2.9% in 2023 (p< 0.001); overweight and obesity from 19.4% in 2014 to 24.1% in 2023 (p< 0.001); current alcohol consumption from 28.5% in 2014, to 31.1% in 2023 (p=0.013); and sedentariness from 26.6% in 2014, to 31.9% in 2023 (p< 0.001). It is only the prevalence of current smoke tobacco use that decreased significantly from 9.6% in 2014, to 8.3% in 2023 (p= 0.046). Nationally, no significant changes were observed in the prevalence of high blood pressure, inadequate consumption of fruits and vegetables, and inadequate physical activity.ConclusionsMost of the common NCD risk factors increased between 2014 and 2023. There is an agent need for the various stakeholders in Uganda to implement interventions targeting reduction in the prevalence of NCD risk factors to prevent the currently increasing burden of NCDs and associated mortality.
The prevalence of chronic kidney disease in people with severe mental illness: A systematic review protocol
Authors: Carswell C. , Bramham K. , Chilcot J. , Jacobs R. , Osborn D. , Siddiqi N. 
Published: September 2024

AbstractBackgroundPeople with severe mental illness (SMI) are more likely to develop long-term physical health conditions, including type 2 diabetes and cardiovascular disease, compared to people without SMI. This contributes to an inequality in life expectancy known as the ‘mortality gap’. Chronic kidney disease (CKD) is a growing global health concern set to be the 5th leading cause of life-years lost by 2040. However, there is limited research exploring the relationship between CKD and SMI. This systematic review will aim to examine the prevalence and incidence of CKD among people with SMI.MethodsWe will search Medline, Embase, PsycINFO, CINAHL, Scopus and Web of Science for primary epidemiological research reporting the prevalence or incidence of CKD among people with SMI in any setting. Retrieved records will be managed in Covidence and screened by two independent reviewers. Data will be extracted from included studies using a piloted data extraction form, and the quality of studies will be evaluated using the appropriate JBI Critical Appraisal Checklist. The certainty of evidence will be assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Data from the included studies will be narratively synthesised. Meta-analyses will be conducted using random effects models to examine the prevalence and incidence of CKD among people with SMI.DiscussionThere is limited research exploring the relationship between CKD and SMI, and this proposed systematic review will be the first to examine the prevalence of CKD among people with SMI. This review will highlight the extent of the problem and provide a foundation for future research to improve health outcomes for people with SMI.
Chemical genetic interactions elucidate pathways controlling tuberculosis antibiotic efficacy during infection
Authors: Oluoch Peter O. , Koh Eun-Ik , Proulx Megan K. , Reames Charlotte J. , Papavinasasundaram Kadamba G. , Murphy Kenan C. , Zimmerman Matthew D. , Dartois Véronique , Sassetti Christopher M. 
Published: September 2024

AbstractSuccessful tuberculosis therapy requires treatment with an unwieldy multidrug combination for several months. Thus, there is a growing need to identify novel genetic vulnerabilities that can be leveraged to develop new, more effective antitubercular drugs. Consequently, recent efforts to optimize TB therapy have exploited Mtb chemical genetics to identify pathways influencing antibiotic efficacy, novel mechanisms of antibiotic action, and new targets for TB drug discovery. However, the influence of the complex host environment on these interactions remains largely unknown, leaving the therapeutic potential of the identified targets unclear. In this study, we leveraged a library of conditional mutants targeting 467 essential Mtb genes to characterize the chemical-genetic interactions (CGIs) with TB drugs directly in the mouse infection model. We found that thesein vivoCGIs differ significantly from those identifiedin vitro. Both drug-specific and drug-agnostic effects were identified, and many were preserved during treatment with a multidrug combination, suggesting numerous strategies for enhancing therapy. This work also elucidated the complex effects of pyrazinamide (PZA), a drug that relies on aspects of the infection environment for efficacy. Specifically, our work supports the importance of coenzyme A synthesis inhibition during infection, as well as the antagonistic effect of iron limitation on PZA activity. In addition, we found that inhibition of thiamine and purine synthesis increases PZA efficacy, suggesting novel therapeutically exploitable metabolic dependencies. Our findings present a map of the uniquein vivoCGIs, characterizing the mechanism of PZA activityin vivoand identifying novel targets for TB drug development.SignificanceThe inevitable rise of multi-drug-resistant tuberculosis underscores the urgent need for new TB drugs and novel drug targets while prioritizing synergistic drug combinations. Chemical-genetic interaction (CGI) studies have delineated bacterial pathways influencing antibiotic efficacy and uncovered druggable pathways that synergize with TB drugs. However, most studies are conductedin vitro, limiting our understanding of how the host environment influences drug-mutant interactions. Using an inducible mutant library targeting essential Mtb genes to characterize CGIs during infection, this study reveals that CGIs are both drug-specific and drug-agnostic and differ significantly from those observedin vitro. Synergistic CGIs comprised distinct metabolic pathways mediating antibiotic efficacy, revealing novel drug mechanisms of action, and defining potential drug targets that would synergize with frontline antitubercular drugs.
Peptide inhibitors targeting FOXO4-p53 interactions and inducing senescent cancer cell-specific apoptosis
Authors: Kang Donghoon , Lim Yeji , Ahn Dabin , Lee Jaeseok , Park Chin-Ju 
Published: September 2024

SummaryCellular senescence, marked by irreversible cell cycle arrest and the secretion of proinflammatory factors, contributes to aging and cancer recurrence. Chemotherapy can also induce senescence; senescent cells often resist apoptosis and promote tumor recurrence. The interaction between FOXO4 and p53 sustains cell survival. Herein, we used biophysical techniques and conducted cellular experiments to develop a peptide inhibitor targeting this interaction to eliminate senescent cancer cells. We identified key regions in the p53 transactivation domain (TAD) involved in FOXO4 binding and designed an optimized peptide inhibitor (CPP-CAND) with improved cell permeability. CPP-CAND showed high selectivity and potency in inducing apoptosis in senescent cells by disrupting FOXO4-p53 foci and activating caspase pathways. It is effective against senescent cancer cells induced by doxorubicin and cisplatin, highlighting its potential as a senolytic drug. Thus, CPP-CAND is a promising therapeutic candidate with improved selectivity, efficacy, and cost-effectiveness.
Polyol sugar osmolyte - sorbitol corrects chromosome cohesion and translational defects in cohesin mutants
Authors: Marathe Sayali , Chougule Haripriya , Nikam Vandana , Majumdar Amitabha , Bose Tania 
Published: September 2024

AbstractThe cohesin protein complex plays a very important role in chromosome segregation, transcription, DNA replication and chromosome condensation. Mutations in cohesin proteins give rise to a disease collectively referred to as Cohesinopathies. The major cause of Cohesinopathies arise due to defects associated with gene expression, that give rise to developmental disorders. In this study, we have usedSaccharomyces cerevisiaeto mimic the Cohesinopathy disorder Roberts syndrome with mutations (eco1W216G) homologous to that of humans (esco2). Our data suggests that polyol sugars like sorbitol, can repair misfolded proteins and reduce ER and proteostatic stress. We have used sorbitol as a chemical chaperone, to check how it can restore chromosome segregation, gene expression, misregulation, protein misfolding, autophagy and translational defects in the cohesin mutant of the Roberts’ phenotype.In silicoscreening has helped us identify the possible sites on eco1, which could be possibly altering the phenotypic traits.Article HighlightsIn presence of sorbitolTemperature sensitivity of the Roberts mutants is rescued.Chromosome cohesion defect is reduced.Translational defects are minimized.Autophagy is enhancedMolecular docking shows its interaction with the acetyltransferase domain of ESCO2.
Nitrous oxide production, mechanisms, and modeling from a denitrifying phosphorus removal bioreactor
Authors: Farmer McKenna , Sabba Fabrizio , Wells George 
Published: September 2024

AbstractNitrous oxide (N2O) is a potent greenhouse gas produced as an unintentional, undesired byproduct in many nitrogen removal bioprocesses. Given the considerable challenges in managing N2O emissions from wastewater treatment, N2O could be reframed as a value-added product if intentionally generated and captured. This study assesses N2O production and mechanisms in a Coupled Aerobic-anoxic Nitrous Decomposition Operation with Phosphorus removal (CANDO+P) reactor. Optimal performance was achieved when the reactor was fed with a mixture of propionate and glucose, resulting in N2O was production up to 50% of influent nitrogen. Through 16S rRNA amplicon and shotgun metagenomic sequencing, we found thatCandidatusAccumulibacter were the dominant phosphorus accumulating organism (PAO). Assembly of a high-quality metagenome-assembled genome showed thatCa.Accumulibacter encoded a full complete denitrification pathway from nitrite to nitrogen gas. We also found abundant populations of denitrifying glycogen accumulating organisms (GAO) and ordinary heterotrophic organisms (OHO). We also incorporated truncated denitrification pathways into a process model to predict N2O generation. N2O predictions were the most similar to observed results when the denitrification pathways of PAO, GAO, and OHO model populations reflected denitrification gene abundances from the metagenomic sequencing analysis. Our work demonstrates the feasibility of using non-VFA carbon for intentional N2O generation and provides broader insights into N2O generation and truncated denitrification pathways of denitrifying PAO and GAO.
Multiple extracellular polymeric substances pathways expressed byAccumulibacterand the flanking community during aerobic granule formation and after influent modification
Authors: Cardona Laëtitia , Saini Jaspreet Singh , Rodilla Ramírez Pilar Natalia , Adler Aline , Holliger Christof 
Published: September 2024

AbstractAerobic granular sludge is a biological wastewater treatment process in which a microbial community forms a granular biofilm. The role ofCandidatusAccumulibacter in the production of a biofilm matrix composed of extracellular polymeric substances was studied in a sequencing batch reactor enriched with polyphosphate-accumulating organisms. The metabolisms of the microbial populations were investigated using de novo metatranscriptomics analysis. Finally, the effect of decreasing the influent phosphate concentration was investigated.A few weeks after the reactor start-up, the microbial community was dominated byAccumulibacter. Up to nine species were active in parallel. However, the most active species differed according to sampling time. Reducing the phosphate concentration led to a dominance of the glycogen-accumulating organismPropionivibrio, with someAccumulibacterspecies still abundant.De novometatranscriptomic analysis indicated a high diversity of potential extracellular substances produced mainly byAzonexus, Accumulibacter, CandidatusContendobacter, andPropionivibrio. Moreover, the results suggest thatAzonexus, ContendobacterandPropionivibriorecycle the neuraminic acid produced byAccumulibacter. Changes in the microbial community did not cause the granules to disintegrate, indicating that aPropionivibrio-dominated community can maintain stable granules.
MLX phosphorylation stabilizes the ChREBP-MLX heterotetramer on tandem E-boxes to control carbohydrate and lipid metabolism
Authors: Cadena del Castillo Carla E , Deniz Onur , van Geest Femke , Rosseels Lore , Stockmans Ingrid , Robciuc Marius , Carpentier Sebastien , Wölnerhanssen Bettina K. , Meyer-Gerspach Anne Christin , Peterli Ralph , Hietakangas Ville , Shimobayashi Mitsugu 
Published: September 2024

AbstractThe heterodimeric ChREBP-MLX transcription factor complex is a key mediator that couples intracellular sugar levels to carbohydrate and lipid metabolism. To promote the expression of target genes, two ChREBP-MLX heterodimers form a heterotetramer to bind a tandem element with two adjacent E-boxes, called Carbohydrate Responsive Element (ChoRE). How the ChREBP-MLX hetero-tetramerization is achieved and regulated, remains poorly understood. Here we show that MLX phosphorylation on an evolutionarily conserved motif is necessary for the heterotetramer formation on the ChoRE and the transcriptional activity of the ChREBP-MLX complex. We identified CK2 and GSK3 as MLX kinases that coordinately phosphorylate MLX. High intracellular glucose-6-phosphate accumulation inhibits MLX phosphorylation and heterotetramer formation on the ChoRE, impairing ChREBP-MLX activity. Physiologically, MLX phosphorylation is necessary inDrosophilato maintain sugar tolerance and lipid homeostasis. Our findings suggest that MLX phosphorylation is a key mechanism for the ChREBP-MLX heterotetramer formation to regulate carbohydrate and lipid metabolism.
TgGloL is an atypical glyoxalase/VOC domain-containing apicoplast protein that is important for the growth ofToxoplasma
Authors: Sanchez Syrian G. , Pouzet Esther , Guimbaud Loïc , Graindorge Arnault , Berry Laurence , Besteiro Sébastien 
Published: September 2024

AbstractGlycolysis is a conserved metabolic pathway that converts glucose into pyruvate in the cytosol, producing ATP and NADH. InToxoplasma gondiiand several other apicomplexan parasites, some glycolytic enzymes have isoforms located in their plastid (called the apicoplast). In this organelle, glycolytic intermediates like glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) are imported from the cytosol and further metabolized, providing ATP, reducing power, and precursors for anabolic pathways such as isoprenoid synthesis. However, GAP and DHAP can spontaneously convert into methylglyoxal, a toxic by-product detoxified by the glyoxalase system, typically involving Glyoxalase-1 (Glo-1) and Glyoxalase-2 (Glo-2). In T. gondii, we identified an atypical protein, TgGloL, containing a Glo-1-like motif but with limited homology to typical Glo enzymes. TgGloL localizes to the apicoplast, and its conditional knockdown impairs parasite growth, indicating its importance. While a specific and direct role for TgGloL in methylglyoxal detoxification within the apicoplast remains unclear, it is crucial for maintaining organelle homeostasis and for overall parasite fitness.
From tissue to subcellular level : imaging human precision-cut lung slices (PCLS) to gain insight into pandemic bacterial or viral infections
Authors: Eymieux Sébastien , Bull-Maurer Anne , Pichon Julien , Sizaret Damien , Maquart Marianne , Carreras Florence , Saint-Vanne Maïa , Doz-Deblauwe Emilie , Bounab Badreddine , Lipan Béatrice , Handala Lynda , Chesnel Florentine , Burlaud-Gaillard Julien , Mammano Fabrizio , Brand Denys , Legras Antoine , Winter Nathalie , Remot Aude 
Published: September 2024

AbstractWe describe a method for the generation and deep imaging of human precision-cut lung slices (PCLS). PCLS bridge the gap betweenin vivoandin vitrostudies, providing a robust system for visualizing events from tissue to subcellular levels in the three-dimensional lung environment, with the preservation of all resident cell types and cell-cell interactions. They also constitute a validated model for studying host cell-pathogen interactions. Here, we detail the generation of human PCLS, followed by their infection and imaging by laser scanning confocal microscopy and transmission electron microscopy (TEM). We establish the conditions forex vivoinfection and replication of two pathogens of relevance to human respiratory health: a virus (SARS-CoV-2) and a bacterium (Mycobacterium tuberculosis,Mtb). PCLS can be obtained in a single day, infected the next day, and were successfully cultivated for up to a week in this study. Imaging was performed on fixed samples. The preparation of PCLS took one day for confocal imaging and five days for TEM imaging. All procedures are readily adaptable to explore other pathogens and other species and are easy to implement by users with experience in tissue culture. Some specialist equipment (an Alabama tissue slicer) is required for PCLS generation.
Fibroblast-specific protein-protein interactions for myocardial fibrosis from MetaCore network
Authors: Frahm Klaus M. , Kotelnikova Ekaterina , Kunduzova Oksana , Shepelyansky Dima L. 
Published: September 2024

AbstractMyocardial fibrosis is a major pathologic disorder associated with a multitude of cardiovascular diseases (CVD). The pathogenesis is complex and encompasses multiple molecular pathways. Integration of fibrosis-associated genes into the global MetaCore network of protein-protein interactions (PPI) offers opportunities to identify PPI with functional and therapeutic significance. Here, we report the generation of a fibrosis-focused PPI network and identification of fibroblast-specific PPI driving reparative and reactive myocardial fibrosis. In TGFb-mediated fibroblast activation, PPI hubs predict new regulatory mechanisms for fibrosis-associated genes. We introduce an efficient Erdös barrage approach to suppress activation of a number of fibrosis-associated nodes in order to reverse fibrotic cascades. Our results suggest that PPI prediction model can offer network insights into fibrosis mechanisms and can complement future experimental efforts to counteract cardiac fibrosis.