Optimizing Object Detection Algorithms for Congenital Heart Diseases in Echocardiography: Exploring Bounding Box Sizes and Data Augmentation Techniques.

Background: Congenital heart diseases (CHDs), particularly atrial and ventricular septal defects, pose significant health risks and common challenges in detection via echocardiography. Doctors often employ the cardiac structural information during the diagnostic process. However, prior CHD research has not determined the influence of including cardiac structural information during the labeling process and the application of data augmentation techniques. Methods: This study utilizes advanced artificial intelligence (AI)-driven object detection frameworks, specifically You Look Only Once (YOLO)v5, YOLOv7, and YOLOv9, to assess the impact of including cardiac structural information and data augmentation techniques on the identification of septal defects in echocardiographic images. Results: The experimental results reveal that different labeling strategies substantially affect the performance of the detection models. Notably, adjustments in bounding box dimensions and the inclusion of cardiac structural details in the annotations are key factors influencing the accuracy of the model. The application of deep learning techniques in echocardiography enhances the precision of detecting septal heart defects. Conclusions: This study confirms that careful annotation of imaging data is crucial for optimizing the performance of object detection algorithms in medical imaging. These findings suggest potential pathways for refining AI applications in diagnostic cardiology studies.

[Potential pathways for traditional Chinese medicine intervention in diabetic kidney disease: macrophage polarization].

Diabetic kidney disease(DKD) is a prevalent and severe microvascular complication of type 2 diabetes mellitus(T2DM). Chronic microinflammation is an important factor exacerbating renal tissue damage in DKD individuals. Macrophages play a crucial role in immune-inflammatory responses, and they can transiently and reversibly polarize into the pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype based on microenvironmental differences. The imbalance in M1/M2 macrophage polarization can exacerbate DKD progression by fostering inflammatory cytokine aggregation in the glomeruli and renal interstitium. Therefore, restoring the balance of macrophage is a pivotal avenue to ameliorate the chronic microinflammation state in DKD. Macrophage polarization is a complex and dynamic process. Various information molecules and cytokines involved in the polarization process play important roles in regulating phenotypes during the progression of DKD. They are closely related to various mechanisms such as metabolism, inflammation, fibrosis, and mitochondrial autophagy in DKD. By coordinating the inflammatory responses through polarization, they play a key role in regulating inflammation in metabolic-related diseases. The complex network of pathways involved in macrophage polarization corresponds well with the multi-pathway, multi-target treatment model of traditional Chinese medicine(TCM). Active ingredients and formulas of TCM can intervene in DKD by regulating macrophage polarization. Studies on relieving renal inflammation, repairing renal tissues, and promoting renal function recovery through macrophage polarization modulation are not uncommon. Therefore, based on exis-ting evidence, this study reviews TCM in targeting M1/M2 macrophage polarization balance to improve DKD, aiming to explore the potential of macrophage polarization in regulating DKD, which is expected to provide evidence support for the clinical diagnosis and treatment of DKD with TCM as well as the exploration of its biological mechanisms.

COVID-19 and diabetes research: Where are we now and what does the future hold? A bibliometric visualization analysis.

Background & objective: The extensive spread of Coronavirus disease 2019 (COVID-19) worldwide has caused a dramatic negative impact on many individuals' health. This study aims to systematically and comprehensively analyze the current status and possible future directions of diabetes mellitus (DM) and COVID-19 research. Methods: We obtained publications about COVID-19 and DM from the Web of Science Core Collection (WoSCC) using the search terms "COVID-19″ and similar terms combined with "DM" and similar terms, with a date range of January 2020 to May 2024. And we used CiteSpace V 6.3.R2 to perform the bibliometric visualization analysis. Results: The search enrolled 6266 publications. The USA is a country with the most publications; Harvard University was the most productive institution in this field. The highest-ranked journal was the PLOS ONE, and the most cited journal was Lancet. The 20 most cited journals have all been cited 28754 times, accounting for 28 % of the total cites; the range of those journals was 790-3197. Publications on COVID-19 and DM research exhibited a distinct trajectory, shifting from an initial emphasis on understanding the impact of diabetes on COVID-19 infection and its associated pathophysiological mechanisms to a focus on analyzing the differential responses of diverse patient populations. Subsequently, research has progressed to examine the effects of medications and vaccines, as well as the long-term consequences of COVID-19 in diabetic individuals. Throughout this research endeavor, the exploration of diverse therapeutic interventions, their efficacy, and ultimate outcomes have consistently remained a paramount focus. And " metabolic syndrome," " long COVID," and " gestational diabetes" are still likely to be the hotspots and frontiers of research in the future. Conclusions: This bibliometric analysis related to DM in COVID-19 illuminates the current research situation and developmental trends, supporting researchers in the exploration of prospective directions for research.

Artificial intelligence empowering rare diseases: a bibliometric perspective over the last two decades.

OBJECTIVE: To conduct a comprehensive bibliometric analysis of the application of artificial intelligence (AI) in Rare diseases (RDs), with a focus on analyzing publication output, identifying leading contributors by country, assessing the extent of international collaboration, tracking the emergence of research hotspots, and detecting trends through keyword bursts. METHODS: In this bibliometric study, we identified and retrieved publications on AI applications in RDs spanning 2003 to 2023 from the Web of Science (WoS). We conducted a global research landscape analysis and utilized CiteSpace to perform keyword clustering and burst detection in this field. RESULTS: A total of 1501 publications were included in this study. The evolution of AI applications in RDs progressed through three stages: the start-up period (2003-2010), the steady development period (2011-2018), and the accelerated growth period (2019-2023), reflecting this field's increasing importance and impact at the time of the study. These studies originated from 85 countries, with the United States as the leading contributor. "Mutation", "Diagnosis", and "Management" were the top three keywords with high frequency. Keyword clustering analysis identified gene identification, effective management, and personalized treatment as three primary research areas of AI applications in RDs. Furthermore, the keyword burst detection indicated a growing interest in the areas of "biomarker", "predictive model", and "data mining", highlighting their potential to shape future research directions. CONCLUSIONS: Over two decades, research on the AI applications in RDs has made remarkable progress and shown promising results in the development. Advancing international transboundary cooperation is essential moving forward. Utilizing AI will play a more crucial role across the spectrum of RDs management, encompassing rapid diagnosis, personalized treatment, drug development, data integration and sharing, and continuous monitoring and care.

Inhibition of Calcineurin with FK506 Reduces Tau Levels and Attenuates Synaptic Impairment Driven by Tau Oligomers in the Hippocampus of Male Mouse Models.

Alzheimer's disease (AD) is the most common age-associated neurodegenerative disorder, characterized by progressive cognitive decline, memory impairment, and structural brain changes, primarily involving Aß plaques and neurofibrillary tangles of hyperphosphorylated tau protein. Recent research highlights the significance of smaller Aß and Tau oligomeric aggregates (AßO and TauO, respectively) in synaptic dysfunction and disease progression. Calcineurin (CaN), a key calcium/calmodulin-dependent player in regulating synaptic function in the central nervous system (CNS) is implicated in mediating detrimental effects of AßO on synapses and memory function in AD. This study aims to investigate the specific impact of CaN on both exogenous and endogenous TauO through the acute and chronic inhibition of CaN. We previously demonstrated the protective effect against AD of the immunosuppressant CaN inhibitor, FK506, but its influence on TauO remains unclear. In this study, we explored the short-term effects of acute CaN inhibition on TauO phosphorylation and TauO-induced memory deficits and synaptic dysfunction. Mice received FK506 post-TauO intracerebroventricular injection and TauO levels and phosphorylation were assessed, examining their impact on CaN and GSK-3ß. The study investigated FK506 preventive/reversal effects on TauO-induced clustering of CaN and GSK-3ß. Memory and synaptic function in TauO-injected mice were evaluated with/without FK506. Chronic FK506 treatment in 3xTgAD mice explored its influence on CaN, Aß, and Tau levels. This study underscores the significant influence of CaN inhibition on TauO and associated AD pathology, suggesting therapeutic potential in targeting CaN for addressing various aspects of AD onset and progression. These findings provide valuable insights for potential interventions in AD, emphasizing the need for further exploration of CaN-targeted strategies.

[Research progress of traditional Chinese medicine in regulating autophagy for intervening in diabetic cardiomyopathy].

Diabetic cardiomyopathy(DCM) is a chronic complication of diabetes mellitus that leads to cardiac damage in the later stages of the disease, and its pathogenesis is complex, involving metabolic disorders brought about by a variety of aberrant alterations such as endoplasmic reticulum stress, oxidative stress, inflammation, and apoptosis, defects in cardiomyocyte Ca~(2+) transporter, and myocardial fibrosis. Currently, there is a lack of specific diagnosis and treatment in the clinic. Autophagy is a highly conserved scavenging mechanism that removes proteins, damaged organelles or foreign contaminants and converts them into energy and amino acids to maintain the stability of the intracellular environment. Inhibition of autophagy can cause harmful metabolites to accumulate in the cell, while over-activation of autophagy can disrupt normal cellular structures and cause cell death. Prolonged high glucose levels disrupt cardiomyocyte autophagy levels and exacerbate the development of DCM. The protective or detrimental effects of autophagy on cells ring true with the traditional Chinese medicine theory of healthy Qi and pathogenic Qi. Autophagy in the physiological state of the removal of intracellular substances and the generation of substances beneficial to the survival of cells is the inhibition of pathogenic Qi to help the performance of healthy Qi, so the organism is healthy. In the early stages of the disease, when autophagy is impaired and incapable of removing waste substances, pathogenic Qi is prevalent; In the later stages of the disease, excessive activation of autophagy can destroy normal cells, leading to a weakening of healthy Qi. Traditional Chinese medicine has the advantage of targeting multiple sites and pathways. Studies in recent years have confirmed that traditional Chinese medicine monomers or formulas can target autophagy, promote the restoration of autophagy levels, maintain mitochondrial and endoplasmic reticulum homeostasis, and reduce oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis in order to prevent and control DCM. This study provides a review of the relationship between autophagy and DCM and the intervention of traditional Chinese medicine in autophagy for the treatment of DCM, with a view to providing new clinical ideas and methods for the treatment of DCM with traditional Chinese medicine.

Dissect the association between per- and polyfluoroalkyl substances (PFAS) and kidney function from the perspective of lipid molecules.

Per- and polyfluoroalkyl substances (PFAS) have been linked to kidney function. Studies have shown that PFAS can cause changes in lipid metabolism and that lipids play an important role in regulating kidney function. However, few studies have explored the overall impact of PFAS mixture on kidney function. Moreover, the mechanisms by which PFAS influences kidney function remain unclear. This study was performed to investigate the overall impact of PFAS mixture on kidney function indexes, dissect the mechanism by which PFAS affect kidney function by analyzing lipid molecule profiles, and analyze the associations between different subclasses of lipids and kidney function indexes. We measured blood PFAS levels and kidney function indexes in a community population containing 278 males. Metabolomic analysis detected 332 lipid molecules. A quantile-based g-computation model was applied to assess the overall effect of PFAS mixture on kidney function index, and revealed that PFAS mixture were associated with a higher level of uric acid (UA). Linear regression analysis demonstrated a positive association between PFOA and UA, and logistic regression analysis indicated a positive association between PFOA and hyperuricemia odds. Notably, none of the PFAS were associated with the estimated glomerular filtration rate, indicating that PFAS didn't have an obvious effect on glomerular filtration. Further analysis identified 20 lipid molecules associated with both PFOA and UA. High-dimensional mediation effect analysis showed that seven lipid molecules (one glycerophospholipid, three fatty acyls, and three prenol lipids) mediated the association between PFOA and UA. Additionally, quantile-based g-computation analysis revealed positive associations between specific lipid subclasses-mainly fatty acid esters, fatty acids and conjugates, and sesquiterpenoids-and kidney function indexes. Our findings provide insights into the renal toxicity of PFAS and may also lead to more in-depth investigations using animal models and other population studies.

Exploring functional and structural connectivity disruptions in spinocerebellar ataxia type 3: Insights from gradient analysis.

AIMS: Spinocerebellar Ataxia Type 3 (SCA3) is a rare genetic ataxia that impacts the entire brain and is characterized as a neurodegenerative disorder affecting the neural network. This study explores how alterations in the functional hierarchy, connectivity, and structural changes within specific brain regions significantly contribute to the heterogeneity of symptom manifestations in patients with SCA3. METHODS: We prospectively recruited 51 patients with SCA3 and 59 age-and sex-matched healthy controls. All participants underwent comprehensive multimodal neuroimaging and clinical assessments. In SCA3 patients, an innovative approach utilizing gradients in resting-state functional connectivity (FC) was employed to examine atypical patterns of hierarchical processing topology from sensorimotor to supramodal regions in the cerebellum and cerebrum. Coupling analyses of abnormal FC and structural connectivity among regions of interest (ROIs) in the brain were also performed to characterize connectivity alterations. Additionally, relationships between quantitative ROI values and clinical variables were explored. RESULTS: Patients with SCA3 exhibited either compression or expansion within the primary sensorimotor-to-supramodal gradient through four distinct calculation methods, along with disruptions in FC and structural connectivity coupling. A comprehensive correlation was identified between the altered gradients and the clinical manifestations observed in patients. Notably, altered fractional anisotropy values were not significantly correlated with clinical variables. CONCLUSION: Abnormal gradients and connectivity in the cerebellar and cerebral cortices in SCA3 patients may contribute to disrupted motor-to-supramodal functions. Moreover, these findings support the potential utility of FCG analysis as a biomarker for diagnosing SCA3 and assessing treatment efficacy.

[Rapid Start-up of Continuous Autotrophic Nitrogen Removal Reactor by Hybrid-inoculating PN and PN/A Granular Sludges].

The rapid cultivation of partial nitritation/ANAMMOX （PN/A） granular sludge in a continuous-flow mode is one of the key technologies for efficient biological nitrogen removal in domestic wastewater treatment. Compared with that in PN/A granular sludge, PN granular sludge demonstrates a shorter incubation period and suitability for batch culture. It is also a good carrier for enriching ANAMMOX （AMX） bacteria. In this study, we established a continuous-flow autotrophic nitrogen removal process in three continuously stirred tank reactors （CSTR） （R1-R3） by hybrid-inoculating PN/A and PN granular sludge at the mass ratios of 3∶1, 1∶1, and 1∶3, respectively. By implementing high ammonium nitrogen loading and short hydraulic retention time, continuous autotrophic nitrogen removal processes were successfully started up in the three CSTRs. The results showed that compared with that of R1 and R2, R3 had a longer start-up time but a similar steady-state nitrogen removal performance. The total nitrogen removal load of R3 could be more than 2.6 kg·ï¼ˆm3·d）-1. Intriguingly, the inoculated PN granular sludge served as a precursor for PN/A granular sludge cultivation. This approach facilitated the enrichment of anaerobic ammonia-oxidizing bacteria （AMX） by introducing abundant ammonium-oxidizing bacteria （AOB） and nitrite nitrogen substrates into the CSTR. According to the results of high-throughput sequencing, the microbial abundance and diversity of the mature granules in R1-R3 were significantly higher than those of the inoculation sludge. AOB （genus Nitrosomonas）, AMX （genera Candidatus Kuenenia and Candidatus Brocadia）, and symbiotic heterotrophs, such as Chloroflexi, Bacteroidetes, and Chlorobi, drove the autotrophic nitrogen removal process and maintained the stability of the granular structure. In summary, a novel start-up strategy of hybrid-inoculating granular sludge was provided for a continuous-flow autotrophic nitrogen removal in engineering application.

[Research progress of traditional Chinese medicines and active ingredients targeting M1/M2 macrophage polarization balance in intervening obese with type 2 diabetes].

Type 2 diabetes(T2DM) is a metabolic disorder marked by glucose toxicity, lipotoxicity, insulin resistance, and other pathological manifestations, representing a pressing global health concern. Obesity stands out as a pivotal risk factor for T2DM development. When combined with T2DM, obesity exacerbates insulin resistance and metabolic abnormalities. The disturbance in the inflammatory microenvironmental balance between adipose and pancreatic islet tissue emerges as a significant contributor to obese with T2DM development. Macrophages play a crucial role in maintaining immune homeostasis and responding to inflammation in adipose and pancreatic islet tissue. Individuals with obese with T2DM exhibit an imbalanced M1/M2 macrophage polarization, contributing to the progression of glycolipid metabolism abnormalities. Hence, restoring the equilibrium of macrophage polarization becomes imperative for obese with T2DM treatment. Scientific researchers have demonstrated that traditional Chinese medicine(TCM) therapies can effectively modulate macrophage polarization, offering a viable approach for treating obese with T2DM. In light of the existing evidence, this study systematically reviewed the research progress of TCM targeting the balance of M1/M2 macrophage polarization to ameliorate obese with T2DM, so as to furnish evidence supporting the clinical diagnosis and treatment of obese with T2DM with TCM while also contributing to the exploration of the biological basis of obese with T2DM.

Effects of methylation and transcription factor YY1 on ID2 expression in non-small cell lung carcinoma cells.

The inhibitor of DNA-binding 2 (ID2) plays a major role in tumor dedifferentiation in non-small cell lung cancer (NSCLC). Studies have indicated an inverse correlation between ID2 expression and NSCLC cell invasiveness. However, the mechanisms through which ID2 activation is regulated are currently unclear. We overexpressed ID2 in H1299 cells and extensively characterized their cellular behaviors. By employing a serial deletion approach combined with a reporter assay, we pinpointed the basal promoter region of ID2. We also examined the DNA methylation status of the ID2 promoter to elucidate the epigenetic mechanisms driving ID2 regulation. Our results revealed that ID2 overexpression effectively inhibited the migration, invasion, proliferation, and colony formation abilities of H1299 cells. The region from -243 to +202 played a major role in driving the transcriptional activity of ID2. Sequence analysis results indicated that the transcription factor Yin Yang 1 (YY1) might be crucial in the regulation of ID2 expression. The ectopically expressed YY1 activated both the expression levels of ID2 and the transcriptional activity of the ID2 promoter, potentially contributing to its repressive activity on cancer cell growth. Furthermore, site-directed mutagenesis and chromatin immunoprecipitation assays revealed that YY1 may target the -120 and -76 sites of the ID2 promoter, thereby activating its transcriptional activity. The ID2 promoter regions were also fully methylated in CL1-5 cells, and the methylation level was correlated with the expression levels of the ID2 promoter. Moreover, the YY1-induced suppression of colony formation was counteracted by ID2 knockdown, which suggests that YY1 represses cell colony growth through the regulation of ID2. Our results indicate that YY1 plays a role in transactivating ID2 expression and might also contribute to the repression of colony growth through the regulation of ID2.

S-scheme heterojunction phthalocyanine/TiO2 photoelectrochemical sensor for innovative glutathione detection.

A novel photoelectrochemical sensor, employing an S-scheme heterojunction of phthalocyanine and TiO2 nanoparticles, has been developed to enable highly sensitive determination of glutathione. By integrating the favorable stability, environmental benignity, and electronic properties of the TiO2 matrix with the unique photoactivity of phthalocyanine species, the designed sensor presents a substantial linear dynamic range and a low detection limit for the quantification of glutathione. The sensitivity is attributed to efficient charge transfer and separation across the staggered heterojunction energy levels, which generates measurable photocurrent signals. Systematic variation of phthalocyanine content reveals an optimal composition that balances light harvesting capacity and electron-hole recombination rates. The incorporation of phosphotungstic acid (PTA) in sample preparation effectively minimizes interference from compounds like L-cysteine and others. Consequently, this leads to an improvement in accuracy through the reduction of impurity levels. Appreciable photocurrent enhancements are observed upon introduction of both oxidized and reduced glutathione at the optimized composite photoanode. Coupled with advantageous features of photoelectrochemical transduction such as simplicity, cost-effectiveness, and resistance to fouling, this sensor holds great promise for practical applications in complex biological media.

Cognitive integrity in Non-Demented Individuals with Alzheimer's Neuropathology is associated with preservation and remodeling of dendritic spines.

INTRODUCTION: Individuals referred to as Non-Demented with Alzheimer's Neuropathology (NDAN) exhibit cognitive resilience despite presenting Alzheimer's disease (AD) histopathological signs. Investigating the mechanisms behind this resilience may unveil crucial insights into AD resistance. METHODS: DiI labeling technique was used to analyze dendritic spine morphology in control (CTRL), AD, and NDAN post mortem frontal cortex, particularly focusing on spine types near and far from amyloid beta (Aß) plaques. RESULTS: NDAN subjects displayed a higher spine density in regions distant from Aß plaques versus AD patients. In distal areas from the plaques, NDAN individuals exhibited more immature spines, while AD patients had a prevalence of mature spines. Additionally, our examination of levels of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1), a protein associated with synaptic plasticity and AD, showed significantly lower expression in AD versus NDAN and CTRL. DISCUSSION: These results suggest that NDAN individuals undergo synaptic remodeling, potentially facilitated by Pin1, serving as a compensatory mechanism to preserve cognitive function despite AD pathology. HIGHLIGHTS: Spine density is reduced near Aß plaques compared to the distal area in CTRL, AD, and NDAN dendrites. NDAN shows higher spine density than AD in areas far from Aß plaques. Far from Aß plaques, NDAN has a higher density of immature spines, AD a higher density of mature spines. AD individuals show significantly lower levels of Pin1 compared to NDAN and CTRL.

AZGP1 deficiency promotes angiogenesis in prostate cancer.

BACKGROUND: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. METHOD: AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples. RESULT: Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1-/- mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues. CONCLUSION: AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.

Comparison of the effectiveness of probiotic supplementation in glucose metabolism, lipid profile, inflammation and oxidative stress in pregnant women.

Objective: The optimal probiotic supplementation in pregnant women has not been thoroughly evaluated. By employing a network meta-analysis (NMA) approach, we compared the effectiveness of different probiotic supplementation strategies for pregnant women. Methods: A comprehensive search across multiple databases was performed to identify studies comparing the efficacy of probiotic supplements with each other or the control (placebo) among pregnant women. Results: This NMA, including 32 studies, systematically evaluated 6 probiotic supplement strategies: Lactobacillus, Lacticaseibacillus rhamnosus and Bifidobacterium (LRB), Lactobacillus acidophilus and Bifidobacterium (LABB), Lactobacillus acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum (LLB), multi-combination of four probiotics (MP1), and multi-combination of six or more probiotics (MP2). Among these strategies, LLB, MP1, and MP2 all contain LABB. The NMA findings showed that MP1 was the most effective in reducing fasting blood sugar (FBS) (surface under the cumulative ranking curve [SUCRA]: 80.5%). In addition, MP2 was the most efficacious in lowering the homeostasis model assessment of insulin resistance (HOMA-IR) (SUCRA: 89.1%). LABB was ranked as the most effective in decreasing low-density lipoprotein cholesterol (LDLC) (SUCRA: 95.5%), total cholesterol (TC) (SUCRA: 95.5%), and high-sensitivity C-reactive protein (hs-CRP) (SUCRA: 94.8%). Moreover, LLB was ranked as the most effective in raising total antioxidant capacity (TAC) (SUCRA: 98.5%). Conclusion: Multi-combination of probiotic strains, especially those strategies containing LABB, may be more effective than a single probiotic strain in glycolipid metabolism, inflammation, and oxidative stress of pregnant women.

Reconstruct recent multi-population migration history by using identical-by-descent sharing.

Identical-by-descent (IBD) is a fundamental genomic characteristic in population genetics and has been widely used for population history reconstruction. However, limited by the nature of IBD, which could only capture the relationship between two individuals/haplotypes, existing IBD-based history inference is constrained to two populations. In this study, we propose a framework by leveraging IBD sharing in multi-population and develop a method, MatrixIBD, to reconstruct recent multi-population migration history. Specifically, we employ the structured coalescent theory to precisely model the genealogical process and then estimate the IBD sharing across multiple populations. Within our model, we establish a theoretical connection between migration history and IBD sharing. Our method is rigorously evaluated through simulations, revealing its remarkable accuracy and robustness. Furthermore, we apply MatrixIBD to Central and South Asia in the Human Genome Diversity Project and successfully reconstruct the recent migration history of three closely related populations in South Asia. By taking into account the IBD sharing across multiple populations simultaneously, MatrixIBD enables us to attain clearer and more comprehensive insights into the history of regions characterized by complex migration dynamics, providing a holistic perspective on intricate patterns embedded within the recent population migration history.

Antibodies against Small Ubiquitin-like Modifier Activating Enzyme May Be a Protective Factor from Rapid Progressive Interstitial Lung Disease in Patients Bearing Antibodies against Melanoma Differentiation Associated Gene 5.

Background: Anti-MDA5 antibody-bearing (anti-MDA5+)-dermatomyositis (DM) or polymyositis (PM) is notorious for causing rapidly progressive interstitial lung disease (RPILD) and/or cancers with high mortality rate. However, anti-MDA5 antibodies (Abs) are also found in other connective tissue diseases and their link with RPILD, especially with regard to the mortality rate, are unknown. Methods: We retrospectively recruited 71 patients bearing anti-MDA5-Abs in serum, stratified them in terms of a presence or absence of RPILD, and evaluated their clinical features, laboratory findings, associated myositis antibodies, concurrent connective tissue disease (CTD) as well as newly developed malignancies. Results: In total, 39 (55%) patients presented with DM/PM, but 32 (45%) did not. In total, 22 of the former and 11 of the latter developed RPILD eventually, accounting for a total of 46% of all MDA-5 bearing patients. On the other hand, 15 of all 71 (21.1%) patients had cancers. Among the 32 patients who did not have DM/PM, 27 (38.0% of all 71) had other CTDs, indicating that only 5 (7.0% of 71) patients did not have CTDs. Senility (odds ratio (OR) = 1.816, p = 0.032), presence of anti-Ro-52 antibody (OR = 1.676, p = 0.018), elevated C-reactive protein (CRP, OR = 4.354, p < 0.001) and carcinoembryonic antigen (CEA, OR = 2.625, p = 0.005) posed risks for RPILD. High lactose dehydrogenase (LDH, p = 0.009), CRP (p = 0.001) and CEA (p = 0.001), ferritin (p ≤ 0.001) and low albumin (p ≤ 0.001) were significantly associated with mortality. Anti-SAE antibodies were negatively correlated with RPILD as analyzed by univariate (OR = 0.245, p = 0.017) and multivariate (OR = 0.058, p = 0.036) regressions, indicating that they may be a protective factor in relation to RPILD (OR = 0.543, p = 0.008) or fatality (OR = 0.707, p = 0.012), which was also demonstrated in subgroup analyses. Conclusions: In contrast to various risk factors for RPILD or mortality, anti-SAE antibodies might conversely be a protective factor in anti-MDA5+ patients.

Artificial intelligence diagnostic model for multi-site fracture X-ray images of extremities based on deep convolutional neural networks.

Background: The rapid and accurate diagnosis of fractures is crucial for timely treatment of trauma patients. Deep learning, one of the most widely used forms of artificial intelligence (AI), is now commonly employed in medical imaging for fracture detection. This study aimed to construct a deep learning model using big data to recognize multiple-fracture X-ray images of extremity bones. Methods: Radiographic imaging data of extremities were retrospectively collected from five hospitals between January 2017 and September 2020. The total number of people finally included was 25,635 and the total number of images included was 26,098. After labeling the lesions, the randomized method used 90% of the data as the training set to develop the fracture detection model, and the remaining 10% was used as the validation set to verify the model. The faster region convolutional neural networks (R-CNN) algorithm was adopted to construct diagnostic models for detection. The Dice coefficient was used to evaluate the image segmentation accuracy. The performances of detection models were evaluated with sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Results: The free-response receiver operating characteristic (FROC) curve value was 0.886 and 0.843 for the detection of single and multiple fractures, respectively. Additionally, the effective identification AUC for all parts was higher than 0.920. Notably, the AUC for wrist fractures reached 0.952. The average accuracy in detecting bone fracture regions in the extremities was 0.865. When analyzing single and multiple lesions at the patient level, the sensitivity was 0.957 for patients with multiple lesions and 0.852 for those with single lesions. In the segmentation task, the training set (the data set used by the machine learning model to train and learn) and the validation set (the data set used to evaluate the performance of the model) reached 0.996 and 0.975, respectively. Conclusions: The faster R-CNN training algorithm exhibits excellent performance in simultaneously identifying fractures in the hands, feet, wrists, ankles, radius and ulna, and tibia and fibula on X-ray images. It demonstrates high accuracy, low false-negative rates, and controllable false-positive rates. It can serve as a valuable screening tool.

Revolutionizing vascular imaging: trends and future directions of 4D flow MRI based on a 20-year bibliometric analysis.

Background: Four-dimensional flow magnetic resonance imaging (4D flow MRI) is a promising new technology with potential clinical value in hemodynamic quantification. Although an increasing number of articles on 4D flow MRI have been published over the past decades, few studies have statistically analyzed these published articles. In this study, we aimed to perform a systematic and comprehensive bibliometric analysis of 4D flow MRI to explore the current hotspots and potential future directions. Methods: The Web of Science Core Collection searched for literature on 4D flow MRI between 2003 and 2022. CiteSpace was utilized to analyze the literature data, including co-citation, cooperative network, cluster, and burst keyword analysis. Results: A total of 1,069 articles were extracted for this study. The main research hotspots included the following: quantification and visualization of blood flow in different clinical settings, with keywords such as "cerebral aneurysm", "heart", "great vessel", "tetralogy of Fallot", "portal hypertension", and "stiffness"; optimization of image acquisition schemes, such as "resolution" and "reconstruction"; measurement and analysis of flow components and patterns, as indicated by keywords "pattern", "KE", "WSS", and "fluid dynamics". In addition, international consensus for metrics derived from 4D flow MRI and multimodality imaging may also be the future research direction. Conclusions: The global domain of 4D flow MRI has grown over the last 2 decades. In the future, 4D flow MRI will evolve towards becoming a relatively short scan duration with adequate spatiotemporal resolution, expansion into the diagnosis and treatment of vascular disease in other related organs, and a shift in focus from vascular structure to function. In addition, artificial intelligence (AI) will assist in the clinical promotion and application of 4D flow MRI.

A Retrospective Study on COVID-19 Infections Caused by Omicron Variant with Clinical, Epidemiological, and Viral Load Evaluations in Breakthrough Infections.

Purpose: To explore the clinical, epidemiological, and viral load characteristics of COVID-19 caused by the omicron variant. Methods: Based on the COVID-19 epidemic caused by SARS-CoV-2 Omicron BA.2 broke out in Shanghai, China. To analyze whether there is any association between clinical symptoms and viral load of COVID-19 with age, sex, and combined disease and whether the clinical symptoms and viral load are associated with vaccine-breakthrough infections. Results: The most common symptoms were cough, expectoration, and fatigue, which were more common in women than males (p < 0.001). The average viral clearance time in the > 75 years group was the longest (6.64 days). The viral load in the 60-75 years group was significantly higher than that in the other groups (p < 0.001). The 18-45 years old group had the most clinical symptoms at admission (45.39%). The days of nucleic acid-negative conversion, average viral load, highest viral load, and clinical symptoms in comorbid chronic disease patients are longer (p < 0.001). The average and highest viral loads in the unvaccinated group were longer than those in the vaccine breakthrough infection groups (p < 0.001). However, the clinical symptoms in the vaccine breakthrough infection group were significantly more severe than those in the unvaccinated group (p < 0.001). Conclusions: We found that female patients, the elderly, and those with underlying comorbidities had longer clinical positive symptoms and viral loads. Although vaccination may not reduce clinical symptoms, it can shorten the viral load and the time required for virus clearance.