Multi-pathways-mediated mechanisms of selenite reduction and elemental selenium nanoparticles biogenesis in the yeast-like fungus Aureobasidium melanogenum I15.

Selenium (Se) plays a critical role in diverse biological processes and is widely used across manufacturing industries. However, the contamination of Se oxyanions also poses a major public health concern. Microbial transformation is a promising approach to detoxify Se oxyanions and produce elemental selenium nanoparticles (SeNPs) with versatile industrial potential. Yeast-like fungi are an important group of environmental microorganisms, but their mechanisms for Se oxyanions reduction remain unknown. In this study, we found that Aureobasidium melanogenum I15 can reduce 1.0 mM selenite by over 90% within 48 h and efficiently form intracellular or extracellular spherical SeNPs. Metabolomic and proteomic analyses disclosed that A. melanogenum I15 evolves a complicated selenite reduction mechanism involving multiple metabolic pathways, including the glutathione/glutathione reductase pathway, the thioredoxin/thioredoxin reductase pathway, the siderophore-mediated pathway, and multiple oxidoreductase-mediated pathways. This study provides the first report on the mechanism of selenite reduction and SeNPs biogenesis in yeast-like fungi and paves an alternative avenue for the bioremediation of selenite contamination and the production of functional organic selenium compounds.

18F-Radiolabeling and Evaluation of an AMD3465 Derivative for PET Imaging of CXCR4 in a Mouse Breast Tumor Model.

The exploration of pharmaceutically active agents and positron emission tomography (PET) tracers targeting CXCR4 has been a focal point in cancer research given its pivotal role in the development and progression of various cancers. While significant strides have been made in PET imaging with radiometal-labeled tracers, the landscape of 18F-labeled small molecule tracers remains relatively limited. Herein, we introduce a novel and promising derivative, [18F]SFB-AMD3465, as a targeted PET tracer for CXCR4. The compound was synthesized by modifying the pyridine ring of AMD3465, which was subsequently labeled with 18F using [18F]SFB. The study provides comprehensive insights into the design, synthesis, and biological evaluation of [18F]SFB-AMD3465. In vitro and in vivo assessments demonstrated the CXCR4-dependent, specific, and sensitive uptake of [18F]SFB-AMD3465 in the CXCR4-overexpressing 4T1 cell line and the corresponding xenograft-bearing mouse model. These findings contribute to bridging the gap in 18F-labeled PET tracers for CXCR4 and underscore the potential of [18F]SFB-AMD3465 as a PET radiotracer for in vivo CXCR4 imaging.

Impact of Synchronous versus Metachronous Metastasis on Outcomes in Patients with Metastatic Renal Cell Carcinoma Treated with First-line Immune Checkpoint Inhibitor-based Combinations.

BACKGROUND AND OBJECTIVE: The impact of time of metastasis onset with respect toprimary renal cell carcinoma (RCC) diagnosis on survival outcomes is not well characterized in the era of immune checkpoint inhibitor (ICI)-based combinations. Herein, we assessed differences in clinical outcomes between synchronous and metachronous metastatic RCC (mRCC). METHODS: Data for patients with mRCC treated with first-line ICI-based combination therapies between 2014 and 2023 were retrospectively collected. Patients were categorized as having synchronous metastasis if present within 3 mo of RCC diagnosis; metachronous metastasis was defined as metastasis >3 mo after primary diagnosis. Time to treatment failure (TTF), overall survival (OS), and the disease control rate (DCR) were assessed. KEY FINDINGS AND LIMITATIONS: Our analysis included 223 eligible patients (126 synchronous and 97 metachronous). Median TTF did not significantly differ between the synchronous and metachronous groups (9 vs 19.8 mo; p = 0.063). Median OS was significantly shorter in the synchronous group (28.0 vs 50.9 mo; p = 0.001). Similarly, patients with synchronous metachronous metastasis (58.7% vs. 78.4%; p = 0.002). On multivariable analyses, synchronous metastasis remained independently associated with worse OS and DCR. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this hypothesis-generating study, patients with mRCC with synchronous metastasis who were treated with first-line ICI-based combinations have a poorer OS and worse DCR than those with metachronous mRCC. If these results are externally validated, time to metastasis could be included in prognostic models for mRCC. PATIENT SUMMARY: Our study demonstrates that patients treated with current first-line immunotherapies, who present with metastasis at the initial diagnosis of kidney cancer have worse overall survival compared to those who develop metastasis later. These results can help physicians and patients understand life expectancy.

Peficitinib alleviated acute lung injury by blocking glycolysis through JAK3/STAT3 pathway.

Peficitinib is a selective Janus kinase (JAK3) inhibitor recently developed and approved for the treatment of rheumatoid arthritis in Japan. Glycolysis in macrophages could induce NOD-like receptor (NLR) family and pyrin domain-containing protein 3 (NLRP3) inflammasome activation, thus resulting in pyroptosis and acute lung injury (ALI). The aim of our study was to investigate whether Peficitinib could alleviate lipopolysaccharide (LPS)-induced ALI by inhibiting NLRP3 inflammasome activation. Wild type C57BL/6J mice were intraperitoneally injected with Peficitinib (5 or 10 mg·kg-1·day-1) for 7 consecutive days before LPS injection. The results showed that Peficitinib pretreatment significantly relieved LPS-induced pulmonary edema, inflammation, and apoptosis. NLRP3 inflammasome and glycolysis in murine lung tissues challenged with LPS were also blocked by Peficitinib. Furthermore, we found that the activation of JAK3/signal transducer and activator of transcription 3 (STAT3) was also suppressed by Peficitinib in mice with ALI. However, in Jak3 knockout mice, Peficitinib did not show obvious protective effects after LPS injection. In vitro experiments further showed that Jak3 overexpression completely abolished Peficitinib-elicited inhibitory effects on pyroptosis and glycolysis in LPS-induced RAW264.7 macrophages. Finally, we unveiled that LPS-induced activation of JAK3/STAT3 was mediated by toll-like receptor 4 (TLR4) in RAW264.7 macrophages. Collectively, our study proved that Peficitinib could protect against ALI by blocking JAK3-mediated glycolysis and pyroptosis in macrophages, which may serve as a promising candidate against ALI in the future.

Efficacy and Safety Assessment of Intrathoracic Perfusion Chemotherapy Combined with immunological factor Interleukin-2 in the Treatment of Advanced Non-Small Cell Lung Cancer: A Retrospective Cohort Study.

Objective: This study evaluated the efficacy and safety of the gemcitabine and oxaliplatin intrathoracic perfusion chemotherapy (IPCGOR) regimen combined with interleukin-2 (IL-2) for advanced non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of 460 advanced NSCLC patients from the Yunnan Province Early Cancer Diagnosis and Treatment Project (June 2020-October 2022), assessing the IPCGOR and IL-2 combination. Outcomes were measured based on RECIST 1.1 criteria, focusing on objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (MOS), and treatment safety. Results: The treatment demonstrated an ORR of 67.4%, a DCR of 97.4%, an mPFS of 8.5 months, and an MOS of 12.5 months. 14 patients underwent successful surgery post-treatment. Common adverse reactions were manageable, with no treatment-related deaths reported. Conclusion: The IPCGOR combined with IL-2 regimen shows promising efficacy and a tolerable safety profile for advanced NSCLC. These findings suggest its potential as a reference for treating advanced NSCLC. However, the study's retrospective nature and single-center design pose limitations. Future research should focus on prospective studies, randomized controlled trials, and long-term outcome assessments, particularly in diverse patient subgroups, to further validate and refine the clinical application of this regimen.

Phylogenetic diversity drives soil multifunctionality in arid montane forest-grassland transition zone.

Exploring plant diversity and ecosystem functioning in different dimensions is crucial to preserve ecological balance and advance ecosystem conservation efforts. Ecosystem transition zones serve as vital connectors linking two distinct ecosystems, yet the impact of various aspects of plant diversity (including taxonomic, functional, and phylogenetic diversity) on soil multifunctionality in these zones remains to be clarified. This study focuses on the forest-grassland transition zone in the mountains on the northern slopes of the Tianshan Mountains, and investigates vegetation and soil characteristics from forest ecosystems to grassland ecosystems to characterize plant diversity and soil functioning, as well as the driving role of plant diversity in different dimensions. In the montane forest-grassland transition zone, urease (URE) and total nitrogen (TN) play a major role in regulating plant diversity by affecting the soil nutrient cycle. Phylogenetic diversity was found to be the strongest driver of soil multifunctionality, followed by functional diversity, while taxonomic diversity was the least important driver. Diverse species were shown to play an important role in maintaining soil multifunctionality in the transition zone, especially distantly related species with high phylogeny. The study of multidimensional plant diversity and soil multifunctionality in the montane forest-grassland transition zone can help to balance the relationship between these two elements, which is crucial in areas where the ecosystem overlaps, and the application of the findings can support sustainable development in these regions.

Urinary biomarkers associated with podocyte injury in lupus nephritis.

The most prevalent and devastating form of organ damage in systemic lupus erythematosus (SLE) is lupus nephritis (LN). LN is characterized by glomerular injury, inflammation, cell proliferation, and necrosis, leading to podocyte injury and tubular epithelial cell damage. Assays for urine biomarkers have demonstrated significant promise in the early detection of LN, evaluation of disease activity, and tracking of reaction to therapy. This is because they are non-invasive, allow for frequent monitoring and easy self-collection, transport and storage. Podocyte injury is believed to be a essential factor in LN. The extent and type of podocyte injury could be connected to the severity of proteinuria, making podocyte-derived cellular debris and injury-related urinary proteins potential markers for the diagnosis and monitoring of LN. This article focuses on studies examining urinary biomarkers associated with podocyte injury in LN, offering fresh perspectives on the application of biomarkers in the early detection and management of LN.

Non-invasive quantification of the brain [18F]FDG-PET using inferred blood input function learned from total-body data with physical constraint.

Full quantification of brain PET requires the blood input function (IF), which is traditionally achieved through an invasive and time-consuming arterial catheter procedure, making it unfeasible for clinical routine. This study presents a deep learning based method to estimate the input function (DLIF) for a dynamic brain FDG scan. A long short-term memory combined with a fully connected network was used. The dataset for training was generated from 85 total-body dynamic scans obtained on a uEXPLORER scanner. Time-activity curves from 8 brain regions and the carotid served as the input of the model, and labelled IF was generated from the ascending aorta defined on CT image. We emphasize the goodness-of-fitting of kinetic modeling as an additional physical loss to reduce the bias and the need for large training samples. DLIF was evaluated together with existing methods in terms of RMSE, area under the curve, regional and parametric image quantifications. The results revealed that the proposed model can generate IFs that closer to the reference ones in terms of shape and amplitude compared with the IFs generated using existing methods. All regional kinetic parameters calculated using DLIF agreed with reference values, with the correlation coefficient being 0.961 (0.913) and relative bias being 1.68±8.74% (0.37±4.93%) for Ki (K1). In terms of the visual appearance and quantification, parametric images were also highly identical to the reference images. In conclusion, our experiments indicate that a trained model can infer an image-derived IF from dynamic brain PET data, which enables subsequent reliable kinetic modeling.

The role of dynamic, static, and delayed total-body PET imaging in the detection and differential diagnosis of oncological lesions.

OBJECTIVES: Commercialized total-body PET scanners can provide high-quality images due to its ultra-high sensitivity. We compared the dynamic, regular static, and delayed 18F-fluorodeoxyglucose (FDG) scans to detect lesions in oncologic patients on a total-body PET/CT scanner. MATERIALS & METHODS: In all, 45 patients were scanned continuously for the first 60 min, followed by a delayed acquisition. FDG metabolic rate was calculated from dynamic data using full compartmental modeling, whereas regular static and delayed SUV images were obtained approximately 60- and 145-min post-injection, respectively. The retention index was computed from static and delayed measures for all lesions. Pearson's correlation and Kruskal-Wallis tests were used to compare parameters. RESULTS: The number of lesions was largely identical between the three protocols, except MRFDG and delayed images on total-body PET only detected 4 and 2 more lesions, respectively (85 total). FDG metabolic rate (MRFDG) image-derived contrast-to-noise ratio and target-to-background ratio were significantly higher than those from static standardized uptake value (SUV) images (P < 0.01), but this is not the case for the delayed images (P > 0.05). Dynamic protocol did not significantly differentiate between benign and malignant lesions just like regular SUV, delayed SUV, and retention index. CONCLUSION: The potential quantitative advantages of dynamic imaging may not improve lesion detection and differential diagnosis significantly on a total-body PET/CT scanner. The same conclusion applied to delayed imaging. This suggested the added benefits of complex imaging protocols must be weighed against the complex implementation in the future. CLINICAL RELEVANCE: Total-body PET/CT was known to significantly improve the PET image quality due to its ultra-high sensitivity. However, whether the dynamic and delay imaging on total-body scanner could show additional clinical benefits is largely unknown. Head-to-head comparison between two protocols is relevant to oncological management.

Tiotropium reduces clinically important deterioration in patients with mild-to-moderate chronic obstructive pulmonary disease: A post hoc analysis of the Tie-COPD study.

BACKGROUND: Clinically important deterioration (CID) is a composite endpoint used to holistically assess the complex progression of chronic obstructive pulmonary disease (COPD). Tiotropium improves lung function and reduces the rate of COPD exacerbations in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate). However, whether tiotropium reduces CID risk in patients with mild-to-moderate COPD remains unclear. METHODS: This was a post hoc analysis of the 24-month Tie-COPD study comparing 18 µg tiotropium with placebo in patients with mild-to-moderate COPD. CID was defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 s, an increase of ≥2 unit in COPD Assessment Test (CAT) score, or moderate-to-severe exacerbation. The time to the first occurrence of one of these events was recorded as the time to the first CID. Subgroup analyses were conducted among patients stratified by CAT score, modified Medical Research Council (mMRC) dyspnea score, and GOLD stage at baseline. RESULTS: Of the 841 randomized patients, 771 were included in the full analysis set. Overall, 643 patients (83.4 %) experienced at least one CID event. Tiotropium significantly reduced the CID risk and delayed the time to first CID compared with placebo (adjusted hazard ratio = 0.58, 95 % confidence interval = 0.49-0.68, P < 0.001). Significant reductions in CID risk were also observed in various subgroups, including patients with a CAT score <10, mMRC score <2, and mild COPD. CONCLUSIONS: Tiotropium reduced CID risk in patients with mild-to-moderate COPD, even in patients with fewer respiratory symptoms or mild disease, which highlights tiotropium's effectiveness in treating COPD patients with mild disease. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (Tie-COPD, NCT01455129).

Two way workable microchanneled hydrogel suture to diagnose, treat and monitor the infarcted heart.

During myocardial infarction, microcirculation disturbance in the ischemic area can cause necrosis and formation of fibrotic tissue, potentially leading to malignant arrhythmia and myocardial remodeling. Here, we report a microchanneled hydrogel suture for two-way signal communication, pumping drugs on demand, and cardiac repair. After myocardial infarction, our hydrogel suture monitors abnormal electrocardiogram through the mobile device and triggers nitric oxide on demand via the hydrogel sutures' microchannels, thereby inhibiting inflammation, promoting microvascular remodeling, and improving the left ventricular ejection fraction in rats and minipigs by more than 60% and 50%, respectively. This work proposes a suture for bidirectional communication that acts as a cardio-patch to repair myocardial infarction, that remotely monitors the heart, and can deliver drugs on demand.

Secular trends of asthma mortality in China and the United States from 1990 to 2019.

BACKGROUND: Asthma imposes a large healthcare burden in China and the United States (US). However, the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the countries. The aim of this study was to compare the mortality and risk factors between China and the US. METHODS: The deaths, and mortality rates of asthma in China and the US during 1990-2019 were obtained from the Global Burden of Disease Study 2019. The age-period-cohort model was used to estimate these mortality rates based on a log-linear scale with additive age, period, and cohort effects. The population attributable fractions of risk factors for asthma were estimated. RESULTS: In 1990-2019, the asthma mortality rate was higher in China than in the US. The crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to 2019. The decline in mortality was more obvious in China. Mortality gap between the two countries was narrowing. A sex difference in asthma mortality was observed with higher mortality in males in China and females in the US. The age effects showed that mortality increased with age in adults older than 20 years, particularly in the elderly. Downward trends were generally observed in the period and cohort rate ratios in both countries, with China experiencing a more obvious decrease. Smoking and high body mass index (BMI) were the leading risk factors for asthma mortality in China and the US, respectively. Mortality attributable to occupational asthmagens and smoking decreased the most in China and the US, respectively. CONCLUSIONS: In 1990-2019, the asthma mortality rate was higher in China than in the US; however, the mortality gap has narrowed. Mortality increased with age in adults. The improvements in asthma death risk with period and birth cohort were more obvious in China than in the US. Smoking, high BMI, and aging are major health problems associated with asthma control. The role of occupational asthmagens in asthma mortality underscores the importance of management and prevention of occupational asthma.

Immunotherapy response in microsatellite stable metastatic colorectal cancer is influenced by site of metastases.

BACKGROUND: Prior studies indicate that colorectal cancer patients with liver metastases did not benefit from regorafenib, nivolumab (REGONIVO) or regorafenib, ipilimumab, nivolumab (RIN) treatments, while those without liver metastases showed significant response. This study explores the impact of metastatic sites on treatment outcomes. METHODS: Chemotherapy-refractory colorectal cancer patients treated with REGONIVO or RIN were evaluated, focusing on 2-month organ-specific response, ORR, PFS and OS based on metastatic sites. RESULTS: Of the 96 patients analyzed (58 REGONIVO, 38 RIN), liver or peritoneal metastases led to poor outcomes, with 0 % ORR, and median PFS of 2.0 and 1.5 months respectively. In contrast, lung-only metastases had an ORR of 56.3 % and a PFS of 14 months. The presence of concurrent LN or other extrahepatic metastatic disease in patients with lung metastatic disease diminished but did not prohibit responses. The 2-month response assessment revealed activity in the lungs, soft tissues, and distant lymph nodes. CONCLUSIONS: REGONIVO and RIN were most active in lung-only metastases. Liver and peritoneal metastases were resistant. Future checkpoint inhibitor trials in MSS colorectal cancer should stratify patients based on metastatic locations.

Assessment of eligibility criteria in renal cell carcinoma trials evaluating systemic therapy.

OBJECTIVES: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative. METHODS: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics. RESULTS: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. CONCLUSION: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world.

Spinal Neuronal miR-124 Inhibits Microglial Activation and Contributes to Preventive Effect of Electroacupuncture on Chemotherapy-Induced Peripheral Neuropathy in Mice.

Chemotherapy-induced peripheral neuropathy (CIPN) is a persistent and irreversible side effect of antineoplastic agents. Patients with CIPN usually show chronic pain and sensory deficits with glove-and-stocking distribution. However, whether spinal neuronal microRNA (miR)-124 is involved in cisplatin-induced peripheral neuropathy remains to be studied. In this study, miR-124 was significantly reduced in the spinal dorsal horn in CIPN mice. Overexpression of neuronal miR-124 induced by injecting adeno-associated virus with neuron-specific promoter into the spinal cord of mice prevented the development of mechanical allodynia, sensory deficits, and the loss of intraepidermal nerve fibers induced by cisplatin. Meanwhile, cisplatin-induced M1 microglia activation and the release of proinflammatory cytokines were significantly inhibited by overexpression of neuronal miR-124. Furthermore, electroacupuncture (EA) treatment upregulated miR-124 expression in the spinal dorsal horn of CIPN mice. Interestingly, downregulation of spinal neuronal miR-124 significantly inhibited the regulatory effect of EA on CIPN and microglia activity as well as spinal neuroinflammation induced by cisplatin. These results demonstrate that spinal neuronal miR-124 is involved in the prevention and treatment of EA on cisplatin-induced peripheral neuropathy in mice. Our findings suggest that spinal neuronal miR-124 might be a potential target for EA effect, and we provide, to our knowledge, a new experimental basis for EA prevention of CIPN.

Molecular Nanoarchitectonics of Natural Photosensitizers and Their Derivatives Nanostructures for Improved Photodynamic Therapy.

Natural photosensitizers (PSs) and their derivatives have drawn ever-increasing attention in photodynamic therapy (PDT) for their wild range of sources, desirable biocompatibility, and good photosensitivity. Nevertheless, many factors such as poor solubility, high body clearance rate, limited tumor targeting ability, and short excitation wavelengths severely hinder their applications in efficient PDT. In recent years, fabricating nanostructures by utilizing molecular assembly technique is proposed to solve these problems. This technique is easy to put into effect, and the assembled nanostructures could improve the physical properties of the PSs so as to meet the requirement of PDT. In this concept, we focus on the construction of natural PSs and their derivatives nanostructures through molecular assembly technique to enhance PDT efficacy (Figure 1). Furthermore, current challenges and future perspectives of natural PSs and their derivatives for efficient PDT are discussed.

Higher risk of osteoporosis in adult-onset asthma than childhood-onset asthma: from genetic and prospective evidence.

Both COA and AOA have a genetically causal effect on osteoporosis. COA and AOA were independently associated with incident osteoporosis, and the risk was greatly higher in AOA. Besides corticosteroids, the increased risk of osteoporosis among asthma patients should be attributed to genetic susceptibility and other asthma medications. PURPOSE/INTRODUCTION: Childhood-onset asthma (COA) differs with adult-onset asthma (AOA) on genetic susceptibility, severity, and co-morbidities. Whether COA or AOA is independently associated with osteoporosis is unexplored. We aimed to determine the effects of COA and AOA on osteoporosis at genetic and individual level. METHODS: We used two-sample Mendelian randomization analysis to explore the causal effects of COA and AOA on osteoporosis. In the UK Biobank cohort, we included 478,289 osteoporosis-free participants at baseline (2006-2010). Participants were classified as non-asthma, COA, and AOA at recruitment. Multivariate Cox regression analysis was used to evaluate the effects of COA, AOA, and multiple asthma medications on incident osteoporosis risk. RESULTS: COA and AOA were causally related to osteoporosis, with odds ratio of 1.007 (95% confidence interval (CI), 1.0003-1.0132) and 1.012 (95% CI, 1.002-1.023), respectively. Multivariate Cox regression analysis suggested that COA (hazard ratio (HR), 1.46; 95% CI, 1.32-1.61) and AOA (HR, 1.70; 95% CI, 1.61-1.80) were independently associated with incident osteoporosis, and the risk was greatly higher in AOA (HR, 1.51; 95% CI, 1.34-1.70). In addition to corticosteroids, monotherapy with leukotriene modifiers (HR, 1.70; 95% CI, 1.20-2.42), long-acting beta agonists (HR, 1.49; 95% CI, 1.18-1.87), and short-acting beta agonists (HR, 1.72; 95% CI1.01-2.93) were independently associated with a higher risk of osteoporosis. CONCLUSIONS: Both COA and AOA have a genetically causal effect on osteoporosis, and the risk of osteoporosis is greatly higher in AOA. Besides corticosteroids, the increased risk of osteoporosis among asthma patients should be attributed to genetic susceptibility and other asthma medications.

TLDA: A transfer learning based dual-augmentation strategy for traditional Chinese Medicine syndrome differentiation in rare disease.

The Traditional Chinese Medicine (TCM) has demonstrated its significant medical value over the decades, particularly during the COVID-19 pandemic. TCM-AI interdisciplinary models have been proposed to model TCM knowledge, diagnosis, and treatment experiments in clinical practice. Among them, numerous models have been developed to simulate the syndrome differentiation process of human TCM doctors for automatic syndrome diagnosis. However, these models are designed for normal scenarios and trained using a supervised learning paradigm which needs tens of thousands of training samples. They fail to effectively differentiate syndromes in rare disease scenarios where the available TCM electronic medical records (EMRs) are very limited for each unique syndrome. To address the challenge of rare diseases, this study proposes a simple yet effective method called Transfer Learning based Dual-Augmentation (TLDA). TLDA aims to augment the limited EMRs at both the sample-level and feature-level, enriching the pathological and medical information during training. Extended experiments involving 11 comparison models, including the state-of-the-art model, demonstrate the effectiveness of TLDA. TLDA outperforms all comparison models by a significant margin. Furthermore, TLDA can also be extended to other medical tasks when the EMRs for diagnosis are limited in samples.

Myocardial Work for Dynamic Monitoring of Myocardial Injury in Neonatal Asphyxia.

To assess the value of parameters of myocardial work for dynamic monitoring of myocardial injury after neonatal asphyxia. Fifty-three neonates with asphyxia admitted within 24 h after delivery were divided into a mild asphyxia group (n = 40) and severe asphyxia group (n = 13). Echocardiography was performed within 24 h post-birth, within 72 h post-birth (48 h after first echo), and during recovery. The left ventricular ejection fraction on M-mode echocardiography and by Simpson's biplane method (LVEF and Bi-EF, respectively), stroke volume (SV), cardiac output (CO), cardiac index (CI), global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), and other parameters were measured. Echocardiographic indicators were compared between groups and over time. GWI was significantly increased at 72 h in the mild asphyxia group (P < 0.05) but showed no significant change over time in the severe asphyxia group (P > 0.05). While GCW increased significantly over time in both groups (P < 0.05), it increased earlier in the mild asphyxia group. Time and grouping factors had independent effects on GWI and GCW (P > 0.05). The characteristics of differences in GWI and GCW between the two groups were different from those for LVEF, Bi-EF, SV, CO, CI, and GLS and their change characteristics with improvement from treatment. GWI and GCW changed significantly during recovery from neonatal asphyxia, and their change characteristics differed between mild and severe asphyxia cases. Myocardial work parameters can be used as valuable supplements to traditional indicators of left ventricular function to dynamically monitor the recovery from myocardial injury after neonatal asphyxia.