A novel non-negative Bayesian stacking modeling method for Cancer survival prediction using high-dimensional omics data.

BACKGROUND: Survival prediction using high-dimensional molecular data is a hot topic in the field of genomics and precision medicine, especially for cancer studies. Considering that carcinogenesis has a pathway-based pathogenesis, developing models using such group structures is a closer mimic of disease progression and prognosis. Many approaches can be used to integrate group information; however, most of them are single-model methods, which may account for unstable prediction. METHODS: We introduced a novel survival stacking method that modeled using group structure information to improve the robustness of cancer survival prediction in the context of high-dimensional omics data. With a super learner, survival stacking combines the prediction from multiple sub-models that are independently trained using the features in pre-grouped biological pathways. In addition to a non-negative linear combination of sub-models, we extended the super learner to non-negative Bayesian hierarchical generalized linear model and artificial neural network. We compared the proposed modeling strategy with the widely used survival penalized method Lasso Cox and several group penalized methods, e.g., group Lasso Cox, via simulation study and real-world data application. RESULTS: The proposed survival stacking method showed superior and robust performance in terms of discrimination compared with single-model methods in case of high-noise simulated data and real-world data. The non-negative Bayesian stacking method can identify important biological signal pathways and genes that are associated with the prognosis of cancer. CONCLUSIONS: This study proposed a novel survival stacking strategy incorporating biological group information into the cancer prognosis models. Additionally, this study extended the super learner to non-negative Bayesian model and ANN, enriching the combination of sub-models. The proposed Bayesian stacking strategy exhibited favorable properties in the prediction and interpretation of complex survival data, which may aid in discovering cancer targets.

An effective urobilin clearance strategy based on paramagnetic beads facilitates microscale proteomic analysis of urine.

Urine provides an ideal source for disease biomarker discovery. High-adhesion contaminants such as urobilin, which are difficult to remove from urine, can severely interfere with urinary proteomic analysis. Here, we aimed to establish a strategy based on single-pot, solid-phase-enhanced sample preparation (SP3) technology to prepare samples for urinary proteomics analysis that almost completely eliminates the impact of urobilin. A systematic evaluation of the effects of two urinary protein precipitation methods, two types of protein lysis buffers, and different ratios of magnetic digestion beads on the identification and quantification of the microscale urinary proteome was conducted. Our results indicate that methanol-chloroform precipitation, coupled with efficient lysis facilitated by urea, and subsequent enzymatic digestion using a mix of hydrophilic and hydrophobic magnetic beads offers the best performance. Further applying this strategy to the urine of patients with benign prostatic hyperplasia, prostate cancer and healthy individuals, combined with a narrow window of data-independent acquisition, FGFR4, MYLK, ORM2, GOLM1, SPP1, CD55, CSF1, DLD and TIMP3 were identified as potential biomarkers to discriminate benign prostatic hyperplasia and prostate cancer patients.

Pioneer factors: nature or nurture?

Chromatin is densely packed with nucleosomes, which limits the accessibility of many chromatin-associated proteins. Pioneer factors (PFs) are usually viewed as a special group of sequence-specific transcription factors (TFs) that can recognize nucleosome-embedded motifs, invade compact chromatin, and generate open chromatin regions. Through this process, PFs initiate a cascade of events that play key roles in gene regulation and cell differentiation. A current debate in the field is if PFs belong to a unique subset of TFs with intrinsic "pioneering activity", or if all TFs have the potential to function as PFs within certain cellular contexts. There are also different views regarding the key feature(s) that define pioneering activity. In this review, we present evidence from the literature related to these alternative views and discuss how to potentially reconcile them. It is possible that both intrinsic properties, like tight nucleosome binding and structural compatibility, and cellular conditions, like concentration and co-factor availability, are important for PF function.

DNA methylation-based high-resolution mapping of long-distance chromosomal interactions in nucleosome-depleted regions.

3C-based methods have significantly advanced our understanding of 3D genome organization. However, it remains a formidable task to precisely capture long-range chromosomal interactions between individual loci, such as those between promoters and distal enhancers. Here, we present Methyltransferase Targeting-based chromosome Architecture Capture (MTAC), a method that maps the contacts between a target site (viewpoint) and the rest of the genome in budding yeast with high resolution and sensitivity. MTAC detects hundreds of intra- and inter-chromosomal interactions within nucleosome-depleted regions (NDRs) that cannot be captured by 4C, Hi-C, or Micro-C. By applying MTAC to various viewpoints, we find that (1) most long-distance chromosomal interactions detected by MTAC reflect tethering by the nuclear pore complexes (NPCs), (2) genes co-regulated by methionine assemble into inter-chromosomal clusters near NPCs upon activation, (3) mediated by condensin, the mating locus forms a highly specific interaction with the recombination enhancer (RE) in a mating-type specific manner, and (4) correlation of MTAC signals among NDRs reveal spatial mixing and segregation of the genome. Overall, these results demonstrate MTAC as a powerful tool to resolve fine-scale long-distance chromosomal interactions and provide insights into the 3D genome organization.

A Comprehensive Review on Circulating cfRNA in Plasma: Implications for Disease Diagnosis and Beyond.

Circulating cfRNA in plasma has emerged as a fascinating area of research with potential applications in disease diagnosis, monitoring, and personalized medicine. Circulating RNA sequencing technology allows for the non-invasive collection of important information about the expression of target genes, eliminating the need for biopsies. This comprehensive review aims to provide a detailed overview of the current knowledge and advancements in the study of plasma cfRNA, focusing on its diverse landscape and biological functions, detection methods, its diagnostic and prognostic potential in various diseases, challenges, and future perspectives.

Description of an anaerobic actinobacterium, Kribbibacterium absianum gen. nov., sp. nov., a new member of the novel family Kribbibacteriaceae fam. nov., and reclassification of the genera Granulimonas and Leptogranulimonas.

Two rod-shaped, obligate anaerobic, Gram-stain-positive bacteria isolated from the pig faeces were designated YH-ols2216 and YH-ols2217T. Analysis of 16S rRNA gene sequences revealed that these isolates were most related to the members of the family Atopobiaceae, within the order Coriobacteriales, and Granulimonas faecalis KCTC 25474T with 92.0 and 92.5% similarities, respectively. The 16S rRNA gene sequence similarity within isolates was 99.9 %; and those between isolates YH-ols2216 and YH-ols2217T, and Atopobium minutum DSM 20586T, the type species of the type genus Atopobium within the family Atopobiaceae, were 88.5 and 88.7 %, respectively. Those between isolates and Coriobacterium glomerans PW2T, the type species of the type genus Coriobacterium within the family Coriobacteriaceae, were 88.7 and 89.1 %, respectively. The multi-locus sequence tree revealed that the isolates, alongside the genera Granulimonas and Leptogranulimonas, formed a distinct cluster between the families Atopobiaceae and Coriobacteriaceae. The average nucleotide identities and digital DNA-DNA hybridization values for the isolates and their most closely related strains ranged from 67.7 to 76.2 % and from 18.4 to 23.3 %, respectively. The main cellular fatty acids of the isolates were C18 : 0 DMA, C18 : 1 ω9c, C18 : 0 12OH, C18 : 0, and C16 : 0. The cell wall contained the peptidoglycan meso-diaminopimelic acid. Lactate was the main end-product of the isolates. The major polar lipids of isolate YH-ols2217T were aminophospholipid, aminolipids, and lipids. Menaquinones were not identified in the cells of the isolates. The DNA G+C contents of isolates YH-ols2216 and YH-ols2217T were 67.5 and 67.6 mol%, respectively. Considering these chemotaxonomic, phenotypic, and phylogenetic properties, Kribbibacteriaceae fam. nov. is proposed within the order Coriobacteriales. YH-ols2216 (=KCTC 25708=NBRC 116429) and YH-ols2217T (=KCTC 25709T=NBRC 116430T) represent a novel taxon within this new family and the name Kribbibacterium absianum gen. nov., sp. nov. is proposed. In addition, the genera Granulimonas and Leptogranulimonas are transferred to the family Kribbibacteriaceae fam. nov.

3α-Hydroxylup-20(29)-ene-23,28-dioic Acid as a Phytogenic Chemical Marker for Authenticating Schefflera octophylla (Lour.) Harms Monofloral Honey.

The monofloral honey from Schefflera octophylla (Lour.) Harms (MH-Sco) are of high economic value due to their rarity and potential medicinal benefits. However, the limited investigations on the relationship of phytogenic components between the plant S. octophylla (P-Sco) and MH-Sco have an impact on MH-Sco authentication. Herein, the tentative phytogenic markers of MH-Sco were screened by comparing the metabolites of MH-Sco obtained by ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS)-based untargeted metabolomics with the identified phytogenic chemicals from P-Sco. Combined with the mass and NMR spectral information, 3α-hydroxylup-20(29)-ene-23,28-dioic acid (HLEDA) was finally identified as the phytogenic marker of MH-Sco. A targeted ultrahigh-performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS)-based method was established and validated based on the purified monomer standard to measure HLEDA levels in honey samples. HLEDA determined in MH-Sco was with the content from 0.303 to 0.440 mg/kg, while HLEDA was absent in honey samples from other botanical origins, indicating the reliability of HLEDA as a chemical marker in MH-Sco authentication. This study provides the theoretical basis and industry guidance for honey quality control for commercial consumption.

Computer-aided diagnosis system for optical diagnosis of colorectal polyps under white light imaging.

OBJECTIVES: This study presents a novel computer-aided diagnosis (CADx) designed for optically diagnosing colorectal polyps using white light imaging (WLI).We aimed to evaluate the effectiveness of the CADx and its auxiliary role among endoscopists with different levels of expertise. METHODS: We collected 2,324 neoplastic and 3,735 nonneoplastic polyp WLI images for model training, and 838 colorectal polyp images from 740 patients for model validation. We compared the diagnostic accuracy of the CADx with that of 15 endoscopists under WLI and narrow band imaging (NBI). The auxiliary benefits of CADx for endoscopists of different experience levels and for identifying different types of colorectal polyps was also evaluated. RESULTS: The CADx demonstrated an optical diagnostic accuracy of 84.49%, showing considerable superiority over all endoscopists, irrespective of whether WLI or NBI was used (P < 0.001). Assistance from the CADx significantly improved the diagnostic accuracy of the endoscopists from 68.84% to 77.49% (P = 0.001), with the most significant impact observed among novice endoscopists. Notably, novices using CADx-assisted WLI outperform junior and expert endoscopists without such assistance. CONCLUSIONS: The CADx demonstrated a crucial role in substantially enhancing the precision of optical diagnosis for colorectal polyps under WLI and showed the greatest auxiliary benefits for novice endoscopists.

Unexplained recurrent high fever observed in a depressed adolescent.

BACKGROUND: Depressive episodes in adolescents are often accompanied by various physical symptoms, but few studies have explored the association between depression and fever, This case study is the first to report the relationship between unexplained recurrent high fever and depression. CASE PRESENTATION: H is a 15 year old adolescent female currently in junior year. 2 + months ago, H gradually felt depressed after a class change. Around the time, the patient suddenly developed chills with no obvious trigger and fever. H was treated with anti-infective and anti-viral treatments all of which did not show significant improvement. No significant abnormality was seen in any of the related examinations. Considering that the patient's anxiety, depression and somatic symptoms were obvious during the course of the disease, she was given venlafaxine hydrochloride extended-release capsule 75 mg/d; tandospirone citrate capsule 10 mg Bid; alprazolam tablets 0.4 mg qn to improve mood and sleep; supplemented with transcranial repetitive magnetic stimulation therapy 2 times/d; visible light therapy 1 time/d and psychological counseling once. Over the 6 days of treatment, the patient's body temperature gradually returned to the normal range and her mood improved significantly. CONCLUSION: Depression should be considered a potential cause of unexplained recurrent fevers in adolescents, even when the temperature is significantly outside the normal range.

In Situ Fabrication of Silver Nanoparticle-Decorated Polymeric Vesicles for Antibacterial Applications.

Silver/polymeric vesicle composite nanoparticles with good antibacterial properties were fabricated in this study. Silver nanoparticles (AgNPs) were prepared in situ on cross-linked vesicle membranes through the reduction of silver nitrate (AgNO3) using polyvinylpyrrolidone (PVP) via coordination bonding between the Ag+ ions and the nitrogen atoms on the vesicles. X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-vis), and transmission electron microscopy (TEM) analyses confirmed the formation of AgNPs on the vesicles. The antibacterial test demonstrated good antibacterial activity against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) for the produced AgNP-decorated vesicles. The minimum inhibitory concentration (MIC) values of the AgNP-decorated vesicles for E. coli and S. aureus were 8.4 and 9.6 µg/mL, respectively. Cell viability analysis on the A549 cells indicated that the toxicity was low when the AgNP concentrations did not exceed the MIC values, and the wound healing test confirmed the good antibacterial properties of the AgNP-decorated vesicles.

Homoharringtonine enhances cytarabine-induced apoptosis in acute myeloid leukaemia by regulating the p38 MAPK/H2AX/Mcl-1 axis.

Acute myeloid leukaemia (AML) is a fatal haematopoietic malignancy and is treated with the conventional combination of cytarabine (Ara-C) and daunorubicin (Dau). The survival rate of AML patients is lower due to the cardiotoxicity of daunorubicin. Clinically, homoharringtonine (HHT) plus Ara-C has been reported to be equally effective as Dau plus Ara-C in some types of AML patients with less toxic effects. We utilized the clinical use of homoharringtonine in combination with Ara-C to test its combination mechanism. We found that the insensitivity of AML cells to cytarabine-induced apoptosis is associated with increased Mcl-1 stability and p38 inactivation. HHT downregulates Mcl-1, phosphorylates H2AX and induces apoptosis by activating p38 MAPK. Inactivation of p38 through inhibitors and siRNA blocks apoptosis, H2AX phosphorylation and Mcl-1 reduction. HHT enhances Ara-C activation of the p38 MAPK signalling pathway, overcoming Ara-C tolerance to cell apoptosis by regulating the p38/H2AX/Mcl-1 axis. The optimal ratio of HHT to Ara-C for synergistic lethality in AML cells is 1:4 (M/M). HHT synergistically induces apoptosis in combination with Ara-C in vitro and prolongs the survival of xenografts. We provide a new mechanism for AML treatment by regulating the p38 MAPK/H2AX/Mcl-1 axis to improve cytarabine therapy.

Association between body mass index and tic disorders in school-age children.

OBJECTIVE: To explore the relationship between body mass index (BMI ) and the severity of tic disorders (TDs) in children 6-14 years old. METHODS: A total of 86 children diagnosed with TDs in a hospital between Jan. 2023 and Sept. 2023 were collected by convenient sampling method, and the general data and TD-specific data were collected and analyzed. RESULTS: Univariate analysis showed that patients with different Yale Global Tic Severity Scale (YGTSS) grades had statistically significant differences in age, BMI, residence, snacking pattern, weekly physical exercise frequency, weekly physical exercise time, and proportion of cesarean birth. Multiple linear regression analysis showed that the YGTSS score grades were related to BMI, snacking pattern, and cesarean birth of the patients. Correlation analysis revealed a positive correlation between BMI grades and the YGTSS score grades, with a higher BMI indicating more severe TDs. Predictive value evaluation showed that BMI, snacking pattern, and cesarean birth had predictive values for TD severity, and the highest value was found in the combined prediction. CONCLUSION: BMI, snacking pattern, and cesarean birth are of predictive values for the severity of TDs. In addition, BMI is positively correlated with the severity of TDs, and a higher BMI suggests more severe TDs.

Overexpression of OsNAR2.1 by OsNAR2.1 promoter increases drought resistance by increasing the expression of OsPLDα1 in rice.

BACKGROUND: pOsNAR2.1:OsNAR2.1 expression could significantly increase nitrogen uptake efficiency and grain yield of rice. RESULT: This study reported the effects of overexpression of OsNAR2.1 by OsNAR2.1 promoter on physiological and agronomic traits associated with drought tolerance. In comparison to the wild-type (WT), the pOsNAR2.1:OsNAR2.1 transgenic lines exhibited a significant improvement in survival rate when subjected to drought stress and then irrigation. Under limited water supply conditions, compared with WT, the photosynthesis and water use efficiency (WUE) of transgenic lines were increased by 39.2% and 28.8%, respectively. Finally, the transgenic lines had 25.5% and 66.4% higher grain yield than the WT under full watering and limited water supply conditions, respectively. Compared with the WT, the agronomic nitrogen use efficiency (NUE) of transgenic lines increased by 25.5% and 66.4% under full watering and limited water supply conditions, and the N recovery efficiency of transgenic lines increased by 29.3% and 50.2%, respectively. The interaction between OsNAR2.1 protein and OsPLDα1 protein was verified by yeast hybrids. After drought treatment, PLDα activity on the plasma membrane of the transgenic line increased 85.0% compared with WT. CONCLUSION: These results indicated that pOsNAR2.1:OsNAR2.1 expression could improve the drought resistance of rice by increasing nitrogen uptake and regulating the expression of OsPLDα1.

Immunotherapy of M2 macrophage derived from exosome-based nanoparticles for spinal cord injury.

Developing biomimetic nanoparticles without off-target side-effects remains a major challenge in spinal cord injury (SCI) immunotherapy. In this paper, we have conducted a drug carrier which is biocompatible macrophages-exocytosed exosome-biomimetic manganese (Mn)-iron prussian blue analogues (MPBs) for SCI immunotherapy. Exosome-sheathed MPBs (E-MPBs) exhibit promoted microglia accumulation, alleviation from H2O2-induced microenvironment and inhibition of apoptosis and inflammation in vitro. In addition, E-MPBs possessed significant tissue repair and neuroprotection in vivo. These properties endowed E-MPBs with great improvement in vivo in function recovery, resulting in anti-neuroinflammation activity and excellent biocompatibility in mice SCI model. As a promising treatment for efficient SCI immunotherapy, these results demonstrate the use of exosome-sheathed biomimetic nanoparticles exocytosed by anti-inflammation cells is feasible.

Effect of "Tiaoshen" acupuncture technique on mild depression and its underlying mechanism: A randomized controlled trial study protocol.

Background: Mild depression is not just a mental disease, but also a serious and long-term public health issue. It affects the quality of life of patients and can quickly develop into major depression. There are currently no effective drug treatments with high efficacy and few adverse reactions. Acupuncture may be an alternative treatment option. Preliminary experiments and practices have demonstrated that "Tiaoshen" acupuncture improves symptoms in patients who have depression, however the underlying data and method remain unclear at present. Methods: This is a prospective, single-center, single-blind, randomized controlled trial. We plan to recruit 70 participants and randomly assign them to receive "Tiaoshen" acupuncture or traditional acupuncture at a ratio of 1:1. Then, all the participants will receive the appropriate acupuncture treatment for four weeks. The results of the Hamilton Depression Rating Scale (HDSR-24) will serve as the primary outcome, while the results of the Patient Health Questionnaire-9 (PHQ-9) and the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) will serve as secondary outcomes. Evaluations will be conducted at baseline, 1, 2, and 4 weeks after treatment initiation, and 1 and 3 months after treatment completion. The safety of the intervention will be evaluated every week using the Columbia-Suicide Severity Rating Scale (C-SSRS) and the Treatment Emergent Symptoms Scale (TESS). Serum levels of oxidative stress markers 8-iso-prostaglandin F2α (8-iso-PGF2α), superoxide dismutase (SOD), uric acid (UA), and total bilirubin (TBIL) will be measured at baseline and the end of the treatment. We will conduct a statistical analysis of intention to treat (ITT) and conformance to protocol set (PPS) data. Discussion: This research aims to provide high-quality evidence for the efficacy and safety of "Tiaoshen" acupuncture as a treatment for mild depression. In addition, the mechanism through which acupuncture heals mild depression will be investigated.

Lysophospholipid acyltransferase-mediated formation of saturated glycerophospholipids maintained cell membrane integrity for hypoxic adaptation.

Adaptation to hypoxia has attracted much public interest because of its clinical significance. However, hypoxic adaptation in the body is complicated and difficult to fully explore. To explore previously unknown conserved mechanisms and key proteins involved in hypoxic adaptation in different species, we first used a yeast model for mechanistic screening. Further multi-omics analyses in multiple species including yeast, zebrafish and mice revealed that glycerophospholipid metabolism was significantly involved in hypoxic adaptation with up-regulation of lysophospholipid acyltransferase (ALE1) in yeast, a key protein for the formation of dipalmitoyl phosphatidylcholine [DPPC (16:0/16:0)], which is a saturated phosphatidylcholine. Importantly, a mammalian homolog of ALE1, lysophosphatidylcholine acyltransferase 1 (LPCAT1), enhanced DPPC levels at the cell membrane and exhibited the same protective effect in mammalian cells under hypoxic conditions. DPPC supplementation effectively attenuated growth restriction, maintained cell membrane integrity and increased the expression of epidermal growth factor receptor under hypoxic conditions, but unsaturated phosphatidylcholine did not. In agreement with these findings, DPPC treatment could also repair hypoxic injury of intestinal mucosa in mice. Taken together, ALE1/LPCAT1-mediated DPPC formation, a key pathway of glycerophospholipid metabolism, is crucial for cell viability under hypoxic conditions. Moreover, we found that ALE1 was also involved in glycolysis to maintain sufficient survival conditions for yeast. The present study offers a novel approach to understanding lipid metabolism under hypoxia and provides new insights into treating hypoxia-related diseases.

Progress of the acyl-Coenzyme A thioester hydrolase family in cancer.

In recent years, the acyl-Coenzyme A thioester hydrolase family (ACOTs) has received wide attention as a key link in lipid metabolism. This family is a class of enzymes that catalyze the hydrolysis of fatty acyl-Coenzyme A, disrupting the thioester bond present within acyl-CoA ester molecules to produce free fatty acids (FFA) and the corresponding coenzyme A (CoA). Such enzymes play a very important role in lipid metabolism through maintaining appropriate levels of intracellular FFA and fatty acyl-CoA as well as CoA. It is broadly divided into two distinct subgroups, the type-I α/ß-hydrolase fold enzyme superfamily and the type-II 'hot dog' fold superfamily. There are currently four human type-I genes and eight human type-II genes. Although the two subgroups catalyze the same reaction, they are not structurally similar, do not share the same sequence homology, and differ greatly in protein executive functions. This review summarizes the classification of the acyl-CoA thioester hydrolase family, an overview of the structural sequences, and advances in digestive, respiratory, and urinary systemic tumors. In order to explore potential specific drug targets and effective interventions, to provide new strategies for tumor prevention and treatment.

Peroxidase gene TaPrx109-B1 enhances wheat tolerance to water deficit via modulating stomatal density.

Increasing the tolerance of crops to water deficit is crucial for the improvement of crop production in water-restricted regions. Here, a wheat peroxidase gene (TaPrx109-B1) belonging to the class III peroxidase gene family was identified and its function in water deficit tolerance was revealed. We demonstrated that overexpression of TaPrx109-B1 reduced leaf H2O2 level and stomatal density, increased leaf relative water content, water use efficiency, and tolerance to water deficit. The expression of TaEPF1 and TaEPF2, two key negative regulators of stomatal development, were significantly upregulated in TaPrx109-B1 overexpression lines. Furthermore, exogenous H2O2 downregulated the expression of TaEPF1 and TaEPF2 and increased stomatal density, while exogenous application of diphenyleneiodonium chloride, a potent NADPH oxidase inhibitor that repressed the synthesis of H2O2, upregulated the expression of TaEPF1 and TaEPF2, decreased stomatal density, and enhanced wheat tolerance to water deficit. These findings suggest that TaPrx109-B1 influences leaf stomatal density by modulation of H2O2 level, and consequently affecting the expression of TaEPF1 and TaEPF2. The results of the field trial showed that overexpressing TaPrx109-B1 increased grain number per spike, which reduced the yield loss caused by water deficiency. Therefore, TaPrx109-B1 has great potential in breeding wheat varieties with improved water deficit tolerance.

Don't judge a book or health app by its cover: User ratings and downloads are not linked to quality.

OBJECTIVE: To analyse the relationship between health app quality with user ratings and the number of downloads of corresponding health apps. MATERIALS AND METHODS: Utilising a dataset of 881 Android-based health apps, assessed via the 300-point objective Organisation for the Review of Care and Health Applications (ORCHA) assessment tool, we explored whether subjective user-level indicators of quality (user ratings and downloads) correlate with objective quality scores in the domains of user experience, data privacy and professional/clinical assurance. For this purpose, we applied spearman correlation and multiple linear regression models. RESULTS: For user experience, professional/clinical assurance and data privacy scores, all models had very low adjusted R squared values (< .02). Suggesting that there is no meaningful link between subjective user ratings or the number of health app downloads and objective quality measures. Spearman correlations suggested that prior downloads only had a very weak positive correlation with user experience scores (Spearman = .084, p = .012) and data privacy scores (Spearman = .088, p = .009). There was a very weak negative correlation between downloads and professional/clinical assurance score (Spearman = -.081, p = .016). Additionally, user ratings demonstrated a very weak correlation with no statistically significant correlations observed between user ratings and the scores (all p > 0.05). For ORCHA scores multiple linear regression had adjusted R-squared = -.002. CONCLUSION: This study highlights that widely available proxies which users may perceive to signify the quality of health apps, namely user ratings and downloads, are inaccurate predictors for estimating quality. This indicates the need for wider use of quality assurance methodologies which can accurately determine the quality, safety, and compliance of health apps. Findings suggest more should be done to enable users to recognise high-quality health apps, including digital health literacy training and the provision of nationally endorsed "libraries".