Exploring UMAP in hybrid models of entropy-based and representativeness sampling for active learning in biomedical segmentation.

In this work, we study various hybrid models of entropy-based and representativeness sampling techniques in the context of active learning in medical segmentation, in particular examining the role of UMAP (Uniform Manifold Approximation and Projection) as a technique for capturing representativeness. Although UMAP has been shown viable as a general purpose dimension reduction method in diverse areas, its role in deep learning-based medical segmentation has yet been extensively explored. Using the cardiac and prostate datasets in the Medical Segmentation Decathlon for validation, we found that a novel hybrid combination of Entropy-UMAP sampling technique achieved a statistically significant Dice score advantage over the random baseline (3.2% for cardiac, 4.5% for prostate), and attained the highest Dice coefficient among the spectrum of 10 distinct active learning methodologies we examined. This provides preliminary evidence that there is an interesting synergy between entropy-based and UMAP methods when the former precedes the latter in a hybrid model of active learning.

Predicting central cervical lymph node metastasis in papillary thyroid microcarcinoma using deep learning.

Background: The aim of this study is to design a deep learning (DL) model to preoperatively predict the occurrence of central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC). Methods: This research collected preoperative ultrasound (US) images and clinical factors of 611 PTMC patients. The clinical factors were analyzed using multivariate regression. Then, a DL model based on US images and clinical factors was developed to preoperatively predict CLNM. The model's efficacy was evaluated using the receiver operating characteristic (ROC) curve, along with accuracy, sensitivity, specificity, and the F1 score. Results: The multivariate analysis indicated an independent correlation factors including age ≥55 (OR = 0.309, p < 0.001), tumor diameter (OR = 2.551, p = 0.010), macrocalcifications (OR = 1.832, p = 0.002), and capsular invasion (OR = 1.977, p = 0.005). The suggested DL model utilized US images achieved an average area under the curve (AUC) of 0.65, slightly outperforming the model that employed traditional clinical factors (AUC = 0.64). Nevertheless, the model that incorporated both of them did not enhance prediction accuracy (AUC = 0.63). Conclusions: The suggested approach offers a reference for the treatment and supervision of PTMC. Among three models used in this study, the deep model relied generally more on image modalities than the data modality of clinic records when making the predictions.

Sesquiterpenes and α-pyrones from an endophytic fungus Xylaria curta YSJ-5.

Chemical investigation of the culture extract of an endophyte Xylaria curta YSJ-5 from Alpinia zerumbet (Pers.) Burtt. et Smith resulted in the isolation of eight previously undescribed compounds including five eremophilane sesquiterpenes xylarcurenes A-E, one norsesquiterpene xylarcurene F, and two α-pyrone derivatives xylarpyrones A-B together with eight known related derivatives. Their chemical structures were extensively established based on the 1D- and 2D-NMR spectroscopic analysis, modified Mosher's method, electronic circular dichroism calculations, single-crystal X-ray diffraction experiments, and the comparison with previous literature data. All these compounds were tested for in vitro cytotoxic, anti-inflammatory, α-glucosidase inhibitory, and antibacterial activities. As a result, 6-pentyl-4-methoxy-pyran-2-one was disclosed to display significant antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with minimal inhibitory concentration value of 6.3 µg/mL.

CellT-Net: A Composite Transformer Method for 2-D Cell Instance Segmentation.

Cell instance segmentation (CIS) via light microscopy and artificial intelligence (AI) is essential to cell and gene therapy-based health care management, which offers the hope of revolutionary health care. An effective CIS method can help clinicians to diagnose neurological disorders and quantify how well these deadly disorders respond to treatment. To address the CIS task challenged by dataset characteristics such as irregular morphology, variation in sizes, cell adhesion, and obscure contours, we propose a novel deep learning model named CellT-Net to actualize effective cell instance segmentation. In particular, the Swin transformer (Swin-T) is used as the basic model to construct the CellT-Net backbone, as the self-attention mechanism can adaptively focus on useful image regions while suppressing irrelevant background information. Moreover, CellT-Net incorporating Swin-T constructs a hierarchical representation and generates multi-scale feature maps that are suitable for detecting and segmenting cells at different scales. A novel composite style named cross-level composition (CLC) is proposed to build composite connections between identical Swin-T models in the CellT-Net backbone and generate more representational features. The earth mover's distance (EMD) loss and binary cross entropy loss are used to train CellT-Net and actualize the precise segmentation of overlapped cells. The LiveCELL and Sartorius datasets are utilized to validate the model effectiveness, and the results demonstrate that CellT-Net can achieve better model performance for dealing with the challenges arising from the characteristics of cell datasets than state-of-the-art models.

Myocardial infarction drives trained immunity of monocytes, accelerating atherosclerosis.

BACKGROUND AND AIMS: Survivors of acute coronary syndromes face an elevated risk of recurrent atherosclerosis-related vascular events despite advanced medical treatments. The underlying causes remain unclear. This study aims to investigate whether myocardial infarction (MI)-induced trained immunity in monocytes could sustain proatherogenic traits and expedite atherosclerosis. METHODS: Apolipoprotein-E deficient (ApoE-/-) mice and adoptive bone marrow transfer chimeric mice underwent MI or myocardial ischaemia-reperfusion (IR). A subsequent 12-week high-fat diet (HFD) regimen was implemented to elucidate the mechanism behind monocyte trained immunity. In addition, classical monocytes were analysed by flow cytometry in the blood of enrolled patients. RESULTS: In MI and IR mice, blood monocytes and bone marrow-derived macrophages exhibited elevated spleen tyrosine kinase (SYK), lysine methyltransferase 5A (KMT5A), and CCHC-type zinc finger nucleic acid-binding protein (CNBP) expression upon exposure to a HFD or oxidized LDL (oxLDL) stimulation. MI-induced trained immunity was transmissible by transplantation of bone marrow to accelerate atherosclerosis in naive recipients. KMT5A specifically recruited monomethylation of Lys20 of histone H4 (H4K20me) to the gene body of SYK and synergistically transactivated SYK with CNBP. In vivo small interfering RNA (siRNA) inhibition of KMT5A or CNBP potentially slowed post-MI atherosclerosis. Sympathetic denervation with 6-hydroxydopamine reduced atherosclerosis and inflammation after MI. Classical monocytes from ST-elevation MI (STEMI) patients with advanced coronary lesions expressed higher SYK and KMT5A gene levels. CONCLUSIONS: The findings underscore the crucial role of monocyte trained immunity in accelerated atherosclerosis after MI, implying that SYK in blood classical monocytes may serve as a predictive factor for the progression of atherosclerosis in STEMI patients.

Growth of alfalfa in the presence of metabolites from a dark septate endophyte strain Alternaria sp. 17463 cultured with a nonionic surfactant and emulsifier.

AIM: Dark septate endophytes (DSE) were widely used in the agriculture and ecological restoration. The objective of this work was to assess the effect of culture media nonionic surfactant and emulsifier on the biomass and metabolites of DSE strain Alternaria sp. 17463. METHODS AND RESULTS: Changes in the composition of DSE metabolites following the addition of Tween 80 during liquid culture of a DSE fungus were analyzed and used in growth tests of alfalfa.Shaking flask fermentation was carried out and the surfactant was fed to the fungus during the fermentation. The residual sugar content and pH declined significantly in the medium and the biomass of DSE increased by 7.27% over controls with no surfactant. Metabolomic analysis showed that adding the surfactant significantly increased the content of 63 metabolites (P < 0.05). These include lipids and lipid-like molecules, organooxygen compounds, amino acids and organic acids, and flavonoids. Enrichment analysis of metabolic pathways indicates that surfactant addition promoted carbohydrate metabolism and amino acid synthesis. A plant hydroponic experiment indicated that these changes in metabolites altered the root structure of alfalfa seedlings. They also promoted significant increases in root length and root surface area, and increased alfalfa total biomass by 50.2%. CONCLUSIONS: The addition of the surfactant promoted sugar utilization by the DSE fungus and increased the synthesis of lipids and amino acids, resulting in the ability of the fungal metabolites to change root structure and promote plant growth.

Nanoclay Drug-Delivery System Loading Potassium Iodide Promotes Endocytosis and Targeted Therapy in Anaplastic Thyroid Cancer.

The rapid proliferative biological behavior of primary foci of anaplastic thyroid cancer (ATC) makes it a lethal tumor. According to the specific iodine uptake capacity of thyroid cells and enhanced endocytosis of ATC cells, we designed a kind of nanoclay drug-loading system and showed a promising treatment strategy for ATC. Introducing potassium iodide (KI) improves the homoaggregation of clay nanoparticles and then affects the distribution of nanoparticles in vivo, which makes KI@DOX-KaolinMeOH enriched almost exclusively in thyroid tissue. Simultaneously, the improvement of dispersibility of KI@DOX-KaolinMeOH changes the target uptake of ATC cells by improving the endocytosis and nanoparticle-induced autophagy, which regulate the production of autolysosomes and autophagy-enhanced chemotherapy, eventually contributing to a tumor inhibition rate of more than 90% in the primary foci of ATC. Therefore, this facile strategy to improve the homoaggregation of nanoclay by introducing KI has the potential to become an advanced drug delivery vehicle in ATC treatment.

Psittacosis caused severe community-acquired pneumonia accompanied by acute hypoxic respiratory failure: a multicenter retrospective cohort study from China.

INTRODUCTION: Psittacosis can cause severe community-acquired pneumonia (CAP). The clinical manifestations of psittacosis range from subclinical to fulminant psittacosis with multi-organ failure. It is essential to summarize the clinical characteristic of patients with severe psittacosis accompanied by acute hypoxic respiratory failure (AHRF). METHODS: This retrospective study included patients with severe psittacosis caused CAP accompanied by AHRF from 19 tertiary hospitals of China. We recorded the clinical data, antimicrobial therapy, respiratory support, complications, and outcomes. Chlamydia psittaci was detected on the basis of metagenomic next-generation sequencing performed on bronchoalveolar lavage fluid samples. Patient outcomes were compared between the treatment methods. RESULTS: This study included 45 patients with severe CAP and AHRF caused by psittacosis from April 2018 to May 2021. The highest incidence of these infections was between September and April. There was a history of poultry contact in 64.4% of the patients. The median PaO2/FiO2 of the patients was 119.8 (interquartile range, 73.2 to 183.6) mmHg. Four of 45 patients (8.9%) died in the ICU, and the median ICU duration was 12 days (interquartile range, 8 to 21) days. There were no significant differences between patients treated with fluoroquinolone initially and continued after the diagnosis, fluoroquinolone initially followed by tetracycline, and fluoroquinolone combined with tetracycline. CONCLUSION: Psittacosis caused severe CAP seems not rare, especially in the patients with the history of exposure to poultry or birds. Empirical treatment that covers atypical pathogens may benefit such patients, which fluoroquinolones might be considered as an alternative.

Age-based factors modulating the required thyroxine dose to achieve thyrotropin suppression in intermediate-and high-risk papillary thyroid cancer.

Background: Guidelines widely recommend thyrotropin suppression to reduce the risk of recurrence in intermediate- and high-risk papillary thyroid cancer (PTC) after total thyroidectomy. However, an insufficient or excessive dosage may result in a number of symptoms/complications especially in older patients. Patients and methods: We constructed a retrospective cohort including 551 PTC patient encounters. Using propensity score matching and logistic regression models, we determined the independent risk factors affecting levothyroxine therapy at different ages. Our outcomes included: expected TSH level and an unexpected TSH level, which was based on the initial thyroid-stimulating hormone (TSH) goal< 0.1 mIU/L with usual dosage of L-T4 (1.6 µg/kg/day). Results: From our analysis, more than 70% of patients undergoing total thyroidectomy did not achieve the expected TSH level using an empirical medication regimen, and the effect of the drug was affected by age (odds ratio [OR], 1.063; 95% CI, 1.032-1.094), preoperative TSH level (OR, 0.554; 95% CI, 0.436-0.704) and preoperative fT3 level (OR, 0.820; 95% CI, 0.727-0.925). In patients with age < 55 years old, preoperative TSH level (OR, 0.588; 95% CI, 0.459-0.753), and preoperative fT3 level (OR, 0.859; 95% CI, 0.746-0.990) were two independent protective factors, while, in patients with age ≥ 55 years old, only preoperative TSH level (OR, 0.490; 95% CI, 0.278-0.861) was the independent protective factors to achieve expected TSH level. Conclusion: Our retrospective analysis suggested the following significant risk factors of getting TSH suppression in PTC patients: age (≥55 years), lower preoperative TSH and fT3 levels.

Entrustable Professional Activities Developed for Allied Health Entry-Level Programs Across a National Level Training Standards Framework in Singapore.

BACKGROUND: Singapore reviewed its national allied health professions (AHP) training framework, aiming to link educational objectives with entrustment and provide clearer transition to entry-level practice. Entrustable Professional Activities (EPAs) were chosen. METHODS: A participatory, iterative, four-phased approach was used to develop the EPAs within and across each AHP's Working Committee (WC). For a harmonized conceptualization of EPAs across the national framework, two steps anchor key considerations: defining EPA phenotypes along the training continuum and identifying competency domains of professional practice for subsequent mapping to EPAs. WC members were purposefully selected from diverse backgrounds and healthcare settings to achieve content validity. RESULTS: Thirty-one allied health EPAs, 5 national AHP competency domains, and 11 subcompetencies were developed altogether for undergraduate diagnostic radiography, dietetics and nutrition, occupational therapy, physiotherapy, radiation therapy and speech and language therapy (SLT) and SLT graduate-entry master's programs in two universities. Core EPAs demonstrated elements of clinical practice common in student training and entry-level work: assessment, planning, implementing intervention and discharging/transferring of care. The entrustment level to be attained in most EPAs by end of program is indirect supervision. CONCLUSION: An aligned national EPA framework for AHP students' training into entry-level may facilitate clearer signposts through entrustment levels.

Modeling ultra-high dose rate electron and proton FLASH effect with the physicochemical approach.

Objective. A physicochemical model built on the radiochemical kinetic theory was recently proposed in (Labarbeet al2020) to explain the FLASH effect. We performed extensive simulations to scrutinize its applicability for oxygen depletion studies and FLASH-related experiments involving both proton and electron beams.Approach. Using the dose and beam delivery parameters for each FLASH experiment, we numerically solved the radiochemical rate equations comprised of a set of coupled nonlinear ordinary differential equations to obtain the area under the curve (AUC) of radical concentrations.Main results. The modeled differences in AUC induced by ultra-high dose rates appeared to correlate well with the FLASH effect. (i) For the whole brain irradiation of mice performed in (Montay-Gruelet al2017), the threshold dose rate values for memory preservation coincided with those at which AUC started to decrease much less rapidly. (ii) For the proton pencil beam scanning FLASH of (Cunninghamet al2021), we found linear correlations between radicals' AUC and the biological endpoints: TGF-ß1, leg contracture and plasma level of cytokine IL-6. (iii) Compatible with the findings of the proton FLASH experiment in (Kimet al2021), we found that radicals' AUC at the entrance and mid-Spread-Out Bragg peak regions were highly similar. In addition, our model also predicted ratios of oxygen depletionG-values between normal and UHDR irradiation similar to those observed in (Caoet al2021) and (El Khatibet al2022).Significance. Collectively, our results suggest that the normal tissue sparing conferred by UHDR irradiation may be due to the lower degree of exposure to peroxyl and superoxide radicals. We also found that the differential effect of dose rate on the radicals' AUC was less pronounced at lower initial oxygen levels, a trait that appears to align with the FLASH differential effect on normal versus tumor tissues.

Effects of dietary chlorogenic acid on ileal intestinal morphology, barrier function, immune factors and gut microbiota of broilers under high stocking density stress.

Aims: The purpose of this research was to assess the effect of chlorogenic acid (CGA) in the diet on ileac structure, barrier function, immunological state, and microbial profile of broiler chickens in a high stocking density (HD) environment. Methods: Four hundred and seventy-six male AA broiler chickens were randomly split into four groups, two with a normal stocking density (ND) of fourteen birds per m2 and two with a high stocking density of twenty-two birds per m2. Each of the treatments consisted of five replicates. One of the two ND and HD groups received the usual feed, while the other two were given at 1.5 g/kg CGA as part of their dietary regimen. Results: The ND CGA group showed a greater increase in villus height and villus height/crypt depth compared to the ND group at 35 and 42 days. The HD group experienced a greater elevation in villus height due to CGA supplementation than the HD group across days 28, 35, and 42. At day 42, the HD group saw a decline in OCLN and ZO-1 mRNA expression in the ileum, but CGA was able to restore them. The HD group experienced a greater rise in OCLN mRNA than the control HD group when supplemented with CGA. The expression of TNF-α, IL-1ß, and IL-6 in the ileum was higher in the HD group, and CGA supplementation enhanced this effect. The HD group experienced a greater rise in IL-10 mRNA expression than the control group following the administration of CGA. The HD group showed reduced alpha diversity and an increase in detrimental microbes such as Turicibacter and Shigella in the gut compared to the ND group, while the HD CGA group saw a reduction in Turicibacter, Shigella, and other harmful microbes. These findings reveal that HD stress suppressed the growth of ileac villi, decreased the expression of tight-junction genes, amplified the expression of inflammatory genes, and disturbed the gut microbiota, ultimately leading to increased intestinal permeability. Conclusion: We conclude that when chickens are given dietary CGA, the disruption of the ileac barrier and increased oxidative damage and inflammation due to HD stress are reduced, which increases ileac integrity and the presence of beneficial intestinal bacteria.

ARA-net: an attention-aware retinal atrophy segmentation network coping with fundus images.

Background: Accurately detecting and segmenting areas of retinal atrophy are paramount for early medical intervention in pathological myopia (PM). However, segmenting retinal atrophic areas based on a two-dimensional (2D) fundus image poses several challenges, such as blurred boundaries, irregular shapes, and size variation. To overcome these challenges, we have proposed an attention-aware retinal atrophy segmentation network (ARA-Net) to segment retinal atrophy areas from the 2D fundus image. Methods: In particular, the ARA-Net adopts a similar strategy as UNet to perform the area segmentation. Skip self-attention connection (SSA) block, comprising a shortcut and a parallel polarized self-attention (PPSA) block, has been proposed to deal with the challenges of blurred boundaries and irregular shapes of the retinal atrophic region. Further, we have proposed a multi-scale feature flow (MSFF) to challenge the size variation. We have added the flow between the SSA connection blocks, allowing for capturing considerable semantic information to detect retinal atrophy in various area sizes. Results: The proposed method has been validated on the Pathological Myopia (PALM) dataset. Experimental results demonstrate that our method yields a high dice coefficient (DICE) of 84.26%, Jaccard index (JAC) of 72.80%, and F1-score of 84.57%, which outperforms other methods significantly. Conclusion: Our results have demonstrated that ARA-Net is an effective and efficient approach for retinal atrophic area segmentation in PM.

EEGformer: A transformer-based brain activity classification method using EEG signal.

Background: The effective analysis methods for steady-state visual evoked potential (SSVEP) signals are critical in supporting an early diagnosis of glaucoma. Most efforts focused on adopting existing techniques to the SSVEPs-based brain-computer interface (BCI) task rather than proposing new ones specifically suited to the domain. Method: Given that electroencephalogram (EEG) signals possess temporal, regional, and synchronous characteristics of brain activity, we proposed a transformer-based EEG analysis model known as EEGformer to capture the EEG characteristics in a unified manner. We adopted a one-dimensional convolution neural network (1DCNN) to automatically extract EEG-channel-wise features. The output was fed into the EEGformer, which is sequentially constructed using three components: regional, synchronous, and temporal transformers. In addition to using a large benchmark database (BETA) toward SSVEP-BCI application to validate model performance, we compared the EEGformer to current state-of-the-art deep learning models using two EEG datasets, which are obtained from our previous study: SJTU emotion EEG dataset (SEED) and a depressive EEG database (DepEEG). Results: The experimental results show that the EEGformer achieves the best classification performance across the three EEG datasets, indicating that the rationality of our model architecture and learning EEG characteristics in a unified manner can improve model classification performance. Conclusion: EEGformer generalizes well to different EEG datasets, demonstrating our approach can be potentially suitable for providing accurate brain activity classification and being used in different application scenarios, such as SSVEP-based early glaucoma diagnosis, emotion recognition and depression discrimination.

Reduced type 3 innate lymphoid cells related to worsening kidney function in renal dysfunction.

Intestinal mucosa barrier injury and immunity imbalance contribute to chronic kidney disease (CKD) progression. Type 3 innate lymphoid cells (ILC3s) are essential for normal intestinal homeostasis. Nevertheless, the relationship between ILC3s and CKD remains largely unknown. The aim of this study was to investigate the relationship linking ILC3s to clinical indicators among patients with renal dysfunction. The levels of circulating ILC3s and dendritic cells, as well as their subsets, in patients with renal dysfunction and healthy controls were determined through flow cytometry. The levels of human plasma granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using enzyme-linked immunosorbent assay. Renal function was evaluated by measuring the estimated glomerular filtration rate (eGFR), as well as the levels of serum creatinine, blood urea nitrogen (BUN), and uric acid. The results revealed that the proportion of peripheral ILC3s was significantly decreased in patients with renal dysfunction. This reduction was positively associated with the levels of eGFR, and inversely associated with the levels of BUN and uric acid. Similarly, the percentage of circulating C-C motif chemokine receptor 6-positive (CCR6 +) ILC3s was also obviously reduced, and demonstrated positive and negative associations with the levels of eGFR and BUN, respectively. Furthermore, the levels of CCR6 + ILC3s correlated positively with those of GM-CSF, as well as type 1 conventional dendritic cells (cDC1s), which also decreased in parallel with kidney function. Thus, the reduction of ILC3s, particularly CCR6 + ILC3s, was related to worsening kidney function in patients with renal dysfunction. This effect may delay renal function impairment by regulating cDC1s via the secretion of GM-CSF, indicating that CCR6 + ILC3s may serve as efficient biomarkers for evaluating kidney function.

Health-related quality of life amongst children with chronic kidney disease in Malaysia: performance of the Bahasa Melayu version of the PedsQL 3.0 ESRD Module : (PedsQL 3.0 VerBATIM: version in Bahasa Melayu. Translated for use in Malaysia).

BACKGROUND: The PedsQL 3.0 End Stage Renal Disease (ESRD) Module is a well-accepted instrument internationally but it is not available in the local language. We aimed to validate the Bahasa Melayu (Malay language) version and determine the health-related quality of life (HRQoL) scores amongst children with CKD in Malaysia. METHODS: The source questionnaire in English was translated into Bahasa Melayu. Linguistic validation guidelines by the MAPI Research Institute were followed. The already validated Bahasa Melayu PedsQL 4.0 Generic Core Scales was used for comparison. Sociodemographic data were collected during the interview. Statistical analyses were performed using SPSS version 25.0. RESULTS: Sixty-nine children aged 8 to 18 with CKD stages 4 and 5, with or without dialysis, and their caregivers were recruited. Mean age was 12.62 ± 2.77 (SD). Evaluation of the PedsQL 3.0 ESRD Module Bahasa Melayu version demonstrated good internal consistency (Cronbach alpha 0.82). There was good agreement between child self-report and parent proxy report in all domains; average intraclass correlation coefficients (ICC) were 0.78, 95% CI (0.71, 0.84). Scores obtained from Generic 4.0 scales correlated with the disease-specific ESRD 3.0 scale, Spearman's rho = 0.32, p = 0.007. The Kruskal-Wallis H test indicated that there were no significant differences between stages of CKD and their respective mean HRQoL score, χ2(2) = 2.88, p = 0.236. CONCLUSIONS: The PedsQL 3.0 ESRD Module Bahasa Melayu version is a reliable and feasible tool for cross-cultural adaptation. A longer prospective study may help better illustrate the quality of life in this group of children.

An active glutamine/α-ketoglutarate/HIF-1α axis prevents pregnancy loss by triggering decidual IGF1+GDF15+NK cell differentiation.

Deficiency of decidual NK (dNK) cell number and function has been widely regarded as an important cause of spontaneous abortion. However, the metabolic mechanism underlying the crosstalk between dNK cells and embryonic trophoblasts during early pregnancy remains largely unknown. Here, we observed that enriched glutamine and activated glutaminolysis in dNK cells contribute to trophoblast invasion and embryo growth by insulin-like growth factor-1 (IGF-1) and growth differentiation factor-15 (GDF-15) secretion. Mechanistically, these processes are dependent on the downregulation of EGLN1-HIF-1α mediated by α-ketoglutarate (α-KG). Blocking glutaminolysis with the GLS inhibitor BPTES or the glutamate dehydrogenase inhibitor EGCG leads to early embryo implantation failure, spontaneous abortion and/or fetal growth restriction in pregnant mice with impaired trophoblast invasion. Additionally, α-KG supplementation significantly alleviated pregnancy loss mediated by defective glutaminolysis in vivo, suggesting that inactivated glutamine/α-ketoglutarate metabolism in dNK cells impaired trophoblast invasion and induced pregnancy loss.

MRI-assessed diaphragmatic function can predict frequent acute exacerbation of COPD: a prospective observational study based on telehealth-based monitoring system.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have considerably high mortality and re-hospitalisation rate. Diaphragmatic dysfunction (DD) is common in COPD patients. However, whether diaphragmatic dysfunction is related to acute exacerbation is yet to be elucidated. This study aimed to evaluate the diaphragm function by magnetic resonance imaging (MRI) in COPD patients and assess whether the impact of DD may help predict AECOPD. METHODS: 20 healthy adult volunteers and 80 COPD patients were enrolled. The diaphragms function parameters were accessed by MRI. Patients were guided to start self-management by the Telehealth-based monitoring system following the enrolment. Events of acute exacerbation of COPD were recorded by the system and confirmed by healthcare providers. Binary univariate and multivariate logistic regression analyses were performed to investigate the factors associated with the frequency of AECOPD. Receiver operating characteristic (ROC) curves were further used to assess the value of prediction indexes. RESULTS: Fifty-nine COPD patients completed a one-year follow-up based on the Telehealth-based monitoring system. The clinical outcomes showed that the diaphragm function parameters at the end of maximal breathing were lower in the COPD group than in the healthy control group (P < 0.05). ANOVA showed significant differences among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages for diaphragm function parameters, including chest wall motion, lung area, upper-lower diameter, and the diaphragm thickening fraction at the end of maximal breathing (P < 0.05). Moreover, significant differences in diaphragm function parameters were observed between patients with infrequent AECOPD (n = 28) and frequent AECOPD (n = 31) based on the frequency of AECOPD (P < 0.05). The diaphragm thickening fraction and the chest wall motion were associated with AECOPD after adjusting for age, sex, BMI, and lung functions, and the combination of predictions showed better accuracy in predicting the frequency of AECOPD. CONCLUSIONS: In COPD patients, diaphragm function parameters correlate with the severity of airflow limitation. The diaphragm thickening fraction and the chest wall motion were associated with the frequency of AECOPD and can predict it.