Development and Validation of an Explainable Deep Learning Model to Predict In-Hospital Mortality for Patients With Acute Myocardial Infarction: Algorithm Development and Validation Study.

BACKGROUND: Acute myocardial infarction (AMI) is one of the most severe cardiovascular diseases and is associated with a high risk of in-hospital mortality. However, the current deep learning models for in-hospital mortality prediction lack interpretability. OBJECTIVE: This study aims to establish an explainable deep learning model to provide individualized in-hospital mortality prediction and risk factor assessment for patients with AMI. METHODS: In this retrospective multicenter study, we used data for consecutive patients hospitalized with AMI from the Chongqing University Central Hospital between July 2016 and December 2022 and the Electronic Intensive Care Unit Collaborative Research Database. These patients were randomly divided into training (7668/10,955, 70%) and internal test (3287/10,955, 30%) data sets. In addition, data of patients with AMI from the Medical Information Mart for Intensive Care database were used for external validation. Deep learning models were used to predict in-hospital mortality in patients with AMI, and they were compared with linear and tree-based models. The Shapley Additive Explanations method was used to explain the model with the highest area under the receiver operating characteristic curve in both the internal test and external validation data sets to quantify and visualize the features that drive predictions. RESULTS: A total of 10,955 patients with AMI who were admitted to Chongqing University Central Hospital or included in the Electronic Intensive Care Unit Collaborative Research Database were randomly divided into a training data set of 7668 (70%) patients and an internal test data set of 3287 (30%) patients. A total of 9355 patients from the Medical Information Mart for Intensive Care database were included for independent external validation. In-hospital mortality occurred in 8.74% (670/7668), 8.73% (287/3287), and 9.12% (853/9355) of the patients in the training, internal test, and external validation cohorts, respectively. The Self-Attention and Intersample Attention Transformer model performed best in both the internal test data set and the external validation data set among the 9 prediction models, with the highest area under the receiver operating characteristic curve of 0.86 (95% CI 0.84-0.88) and 0.85 (95% CI 0.84-0.87), respectively. Older age, high heart rate, and low body temperature were the 3 most important predictors of increased mortality, according to the explanations of the Self-Attention and Intersample Attention Transformer model. CONCLUSIONS: The explainable deep learning model that we developed could provide estimates of mortality and visual contribution of the features to the prediction for a patient with AMI. The explanations suggested that older age, unstable vital signs, and metabolic disorders may increase the risk of mortality in patients with AMI.

A SIMPLE, QUICK, AND ECONOMICAL METHOD FOR IN VITRO CULTIVATION OF ECHINOCOCCUS MULTILOCULARIS METACESTODE AND GENERATION OF PRIMARY CELLS.

Alveolar echinococcosis is considered to be one of the most potentially lethal parasitic zoonotic diseases. However, the molecular mechanisms by which Echinococcus multilocularis interacts with hosts are poorly understood, hindering the prevention and treatment of this disease. Due to the great advantages of cell culture systems for molecular research, numerous attempts have been made to establish primary cell cultures for E. multilocularis. In this study we developed a simple, rapid, and economical method that allows E. multilocularis metacestode tissue blocks to generate daughter vesicles without the continuous presence of host feeder cells in a regular medium. We performed anaerobic, hypoxic (1% O2), normoxic, and semi-anaerobic (in sealed tubes) cultures and found that E. multilocularis metacestode tissues can produce daughter vesicles only in the sealed tubes after 4 wk of incubation. The daughter vesicles cultivated in this system were remarkably enlarged under anaerobic conditions after 8 days of culture, whereas vesicles cultured under hypoxic (1% O2) and normoxic conditions showed only a mild increase in volume. Our in vitro cultivated vesicles showed strong viability and could be used to test antiparasitic drugs, isolate primary cells, and infect animals.

Structural optimization of Moracin M as novel selective phosphodiesterase 4 inhibitors for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high mortality lung disease. Although the antifibrotic drugs pirfenidone and nintedanib could slow the rate of lung function decline, the usual course of the condition is inexorably to respiratory failure and death. Therefore, new approaches and novel therapeutic drugs for the treatment of IPF are urgently needed. And the selective PDE4 inhibitor has in vivo and in vitro anti-fibrotic effects in IPF models. But the clinical application of most PDE4 inhibitors are limited by their unexpected and severe side effects such as nausea, vomiting, and diarrhea. Herein, structure-based optimizations of the natural product Moracin M resulted in a novel a novel series of 2-arylbenzofurans as potent PDE4 inhibitors. The most potent inhibitor L13 has an IC50 of 36 ± 7 nM with remarkable selectivity across the PDE families and administration of L13·citrate (10.0 mg/kg) exhibited comparable anti-pulmonary fibrosis effects to pirfenidone (300 mg/kg) in a bleomycin-induced IPF mice model, indicate that L13 is a potential lead for the treatment of IPF.

Development of an orally bioavailable mSWI/SNF ATPase degrader and acquired mechanisms of resistance in prostate cancer.

Mammalian switch/sucrose nonfermentable (mSWI/SNF) ATPase degraders have been shown to be effective in enhancer-driven cancers by functioning to impede oncogenic transcription factor chromatin accessibility. Here, we developed AU-24118, an orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of mSWI/SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients. Importantly, AU-24118 exhibited favorable pharmacokinetic profiles in preclinical analyses in mice and rats, and further toxicity testing in mice showed a favorable safety profile. As acquired resistance is common with targeted cancer therapeutics, experiments were designed to explore potential mechanisms of resistance that may arise with long-term mSWI/SNF ATPase PROTAC treatment. Prostate cancer cell lines exposed to long-term treatment with high doses of a mSWI/SNF ATPase degrader developed SMARCA4 bromodomain mutations and ABCB1 (ATP binding cassette subfamily B member 1) overexpression as acquired mechanisms of resistance. Intriguingly, while SMARCA4 mutations provided specific resistance to mSWI/SNF degraders, ABCB1 overexpression provided broader resistance to other potent PROTAC degraders targeting bromodomain-containing protein 4 and AR. The ABCB1 inhibitor, zosuquidar, reversed resistance to all three PROTAC degraders tested. Combined, these findings position mSWI/SNF degraders for clinical translation for patients with enhancer-driven cancers and define strategies to overcome resistance mechanisms that may arise.

Association of preoperative coronavirus disease 2019 with mortality, respiratory morbidity and extrapulmonary complications after elective, noncardiac surgery: An observational cohort study.

STUDY OBJECTIVE: To assess the impact of preoperative infection with the contemporary strain of severe acute respiratory coronavirus 2 (SARS-CoV-2) on postoperative mortality, respiratory morbidity and extrapulmonary complications after elective, noncardiac surgery. DESIGN: An ambidirectional observational cohort study. SETTING: A tertiary and teaching hospital in Shanghai, China. PATIENTS: All adult patients (≥ 18 years of age) who underwent elective, noncardiac surgery under general anesthesia at Huashan Hospital of Fudan University from January until March 2023 were screened for eligibility. A total of 2907 patients were included. EXPOSURE: Preoperative coronavirus disease 2019 (COVID-19) positivity. MEASUREMENTS: The primary outcome was 30-day postoperative mortality. The secondary outcomes included postoperative pulmonary complications (PPCs), myocardial injury after noncardiac surgery (MINS), acute kidney injury (AKI), postoperative delirium (POD) and postoperative sleep quality. Multivariable logistic regression was used to assess the risk of postoperative mortality and morbidity imposed by preoperative COVID-19. MAIN RESULTS: The risk of 30-day postoperative mortality was not associated with preoperative COVID-19 [adjusted odds ratio (aOR), 95% confidence interval (CI): 0.40, 0.13-1.28, P = 0.123] or operation timing relative to diagnosis. Preoperative COVID-19 did not increase the risk of PPCs (aOR, 95% CI: 0.99, 0.71-1.38, P = 0.944), MINS (aOR, 95% CI: 0.54, 0.22-1.30; P = 0.168), or AKI (aOR, 95% CI: 0.34, 0.10-1.09; P = 0.070) or affect postoperative sleep quality. Patients who underwent surgery within 7 weeks after COVID-19 had increased odds of developing delirium (aOR, 95% CI: 2.26, 1.05-4.86, P = 0.036). CONCLUSIONS: Preoperative COVID-19 or timing of surgery relative to diagnosis did not confer any added risk of 30-day postoperative mortality, PPCs, MINS or AKI. However, recent COVID-19 increased the risk of POD. Perioperative brain health should be considered during preoperative risk assessment for COVID-19 survivors.

Development of an orally bioavailable mSWI/SNF ATPase degrader and acquired mechanisms of resistance in prostate cancer.

Mammalian switch/sucrose non-fermentable (mSWI/SNF) ATPase degraders have been shown to be effective in enhancer-driven cancers by functioning to impede oncogenic transcription factor chromatin accessibility. Here, we developed AU-24118, a first-in-class, orally bioavailable proteolysis targeting chimera (PROTAC) degrader of mSWI/SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients. Importantly, AU-24118 exhibited favorable pharmacokinetic profiles in preclinical analyses in mice and rats, and further toxicity testing in mice showed a favorable safety profile. As acquired resistance is common with targeted cancer therapeutics, experiments were designed to explore potential mechanisms of resistance that may arise with long-term mSWI/SNF ATPase PROTAC treatment. Prostate cancer cell lines exposed to long-term treatment with high doses of a mSWI/SNF ATPase degrader developed SMARCA4 bromodomain mutations and ABCB1 overexpression as acquired mechanisms of resistance. Intriguingly, while SMARCA4 mutations provided specific resistance to mSWI/SNF degraders, ABCB1 overexpression provided broader resistance to other potent PROTAC degraders targeting bromodomain-containing protein 4 (BRD4) and AR. The ABCB1 inhibitor, zosuquidar, reversed resistance to all three PROTAC degraders tested. Combined, these findings position mSWI/SNF degraders for clinical translation for patients with enhancer-driven cancers and define strategies to overcome resistance mechanisms that may arise.

Integrative Dissection of Lignin Composition in Tartary Buckwheat Seed Hulls for Enhanced Dehulling Efficiency.

The rigid hull encasing Tartary buckwheat seeds necessitates a laborious dehulling process before flour milling, resulting in considerable nutrient loss. Investigation of lignin composition is pivotal in understanding the structural properties of tartary buckwheat seeds hulls, as lignin is key determinant of rigidity in plant cell walls, thus directly impacting the dehulling process. Here, the lignin composition of seed hulls from 274 Tartary buckwheat accessions is analyzed, unveiling a unique lignin chemotype primarily consisting of G lignin, a common feature in gymnosperms. Furthermore, the hardness of the seed hull showed a strong negative correlation with the S lignin content. Genome-wide detection of selective sweeps uncovered that genes governing the biosynthesis of S lignin, specifically two caffeic acid O-methyltransferases (COMTs) and one ferulate 5-hydroxylases, are selected during domestication. This likely contributed to the increased S lignin content and decreased hardness of seed hulls from more domesticated varieties. Genome-wide association studies identified robust associations between FtCOMT1 and the accumulation of S lignin in seed hull. Transgenic Arabidopsis comt1 plants expressing FtCOMT1 successfully reinstated S lignin content, confirming its conserved function across plant species. These findings provide valuable metabolic and genetic insights for the potential redesign of Tartary buckwheat seed hulls.

A short-term price prediction-based trading strategy.

Quantitative investment theory has emerged as a prominent and widely researched domain within the financial markets, where investors predominantly focus on discerning the intricate influences of market dynamics. In this paper, we proposed a short-term prediction-based trading strategy, which can equiponderate between return and risk, considerations while accounting for investor risk preferences. This strategy employs GM(1,1) to capture nuanced features of price dynamics in short-term intervals and update the GM(1,1) model with the latest data. Subsequently, a multi-objective planning equation is formulated to optimize asset allocations by determining the optimal holding that strikes between specific returns and risk mitigation. In the end, this work conducts a case study and sensitivity analysis using five years of gold and bitcoin price data spanning from 2016 to 2021. This empirical examination serves to affirm the efficacy and resilience of the proposed trading strategy. The case study reveals that proficient short-term price forecasting serves as a potent means to proactively mitigate risk, facilitating, judicious and objective trading practices. Moreover, it underscores the strategy's tangible utility as a guide for real-world investment decisions.

Hydrogel immobilized bacteria@MOFs composite towards Bisphenol A degradation and the interconnection mechanism elucidation.

Bisphenol A (BPA) degradation efficiency by bacteria or by metal-organic-frameworks (MOFs) catalyzed persulfate (PMS) oxidation have been studied intensively. However, their synergistic effect on BPA degradation was less reported. In this study, we combined previously synthesized CNT-hemin/Mn-MOF with an BPA degrading bacteria SQ-2 to form a composite (SQ-2@MOFs). CNT-hemin/Mn-MOF in the composite catalyzed little PMS to promote the degradation efficiency of SQ-2 on BPA. Results indicated SQ-2@MOFs significantly accelerated BPA degradation rate than SQ-2 alone. Furthermore, SQ-2@MOFs composite was successfully immobilized in hydrogel to achieve better degradation performance. Immobilized SQ-2@MOFs could almost completely degrade 1-20 mg/L BPA within 24 h and completely degrade 5 mg/L BPA at pH 4-8. Besides, degradation byproducts also reduced by immobilized SQ-2@MOFs, which promoted the cleaner biodegradation of BPA. Metabolomics and multiple chemical characterization results revealed the interconnection mechanism between CNT-hemin/Mn-MOFs, SQ-2 and hydrogel. CNT-hemin/Mn-MOF helped SQ-2 degrade BPA into more biodegradable products, promoted electron transfer, and augmented BPA degradation ability of SQ-2 itself. SQ-2 enabled the surface electronegativity of SQ-2@MOFs more suitable for BPA contact. Meanwhile, SQ-2 avoided the loss of Fe and Mn of CNT-hemin/Mn-MOF. Hydrogel augmented the above synergistic effect. This study provided new perspective for the development of biodegradation materials through interdisciplinary integration.

Machine Learning Empowering Drug Discovery: Applications, Opportunities and Challenges.

Drug discovery plays a critical role in advancing human health by developing new medications and treatments to combat diseases. How to accelerate the pace and reduce the costs of new drug discovery has long been a key concern for the pharmaceutical industry. Fortunately, by leveraging advanced algorithms, computational power and biological big data, artificial intelligence (AI) technology, especially machine learning (ML), holds the promise of making the hunt for new drugs more efficient. Recently, the Transformer-based models that have achieved revolutionary breakthroughs in natural language processing have sparked a new era of their applications in drug discovery. Herein, we introduce the latest applications of ML in drug discovery, highlight the potential of advanced Transformer-based ML models, and discuss the future prospects and challenges in the field.

Targeting the mSWI/SNF Complex in POU2F-POU2AF Transcription Factor-Driven Malignancies.

The POU2F3-POU2AF2/3 (OCA-T1/2) transcription factor complex is the master regulator of the tuft cell lineage and tuft cell-like small cell lung cancer (SCLC). Here, we found that the POU2F3 molecular subtype of SCLC (SCLC-P) exhibits an exquisite dependence on the activity of the mammalian switch/sucrose non-fermentable (mSWI/SNF) chromatin remodeling complex. SCLC-P cell lines were sensitive to nanomolar levels of a mSWI/SNF ATPase proteolysis targeting chimera (PROTAC) degrader when compared to other molecular subtypes of SCLC. POU2F3 and its cofactors were found to interact with components of the mSWI/SNF complex. The POU2F3 transcription factor complex was evicted from chromatin upon mSWI/SNF ATPase degradation, leading to attenuation of downstream oncogenic signaling in SCLC-P cells. A novel, orally bioavailable mSWI/SNF ATPase PROTAC degrader, AU-24118, demonstrated preferential efficacy in the SCLC-P relative to the SCLC-A subtype and significantly decreased tumor growth in preclinical models. AU-24118 did not alter normal tuft cell numbers in lung or colon, nor did it exhibit toxicity in mice. B cell malignancies which displayed a dependency on the POU2F1/2 cofactor, POU2AF1 (OCA-B), were also remarkably sensitive to mSWI/SNF ATPase degradation. Mechanistically, mSWI/SNF ATPase degrader treatment in multiple myeloma cells compacted chromatin, dislodged POU2AF1 and IRF4, and decreased IRF4 signaling. In a POU2AF1-dependent, disseminated murine model of multiple myeloma, AU-24118 enhanced survival compared to pomalidomide, an approved treatment for multiple myeloma. Taken together, our studies suggest that POU2F-POU2AF-driven malignancies have an intrinsic dependence on the mSWI/SNF complex, representing a therapeutic vulnerability.

Tumor-associated macrophages in colorectal cancer metastasis: molecular insights and translational perspectives.

Metastasis is the leading cause of high mortality in colorectal cancer (CRC), which is not only driven by changes occurring within the tumor cells, but is also influenced by the dynamic interaction between cancer cells and components in the tumor microenvironment (TME). Currently, the exploration of TME remodeling and its impact on CRC metastasis has attracted increasing attention owing to its potential to uncover novel therapeutic avenues. Noteworthy, emerging studies suggested that tumor-associated macrophages (TAMs) within the TME played important roles in CRC metastasis by secreting a variety of cytokines, chemokines, growth factors and proteases. Moreover, TAMs are often associated with poor prognosis and drug resistance, making them promising targets for CRC therapy. Given the prognostic and clinical value of TAMs, this review provides an updated overview on the origin, polarization and function of TAMs, and discusses the mechanisms by which TAMs promote the metastatic cascade of CRC. Potential TAM-targeting techniques for personalized theranostics of metastatic CRC are emphasized. Finally, future perspectives and challenges for translational applications of TAMs in CRC development and metastasis are proposed to help develop novel TAM-based strategies for CRC precision medicine and holistic healthcare.

Temporal and spatial effects on C-reactive protein's regulation of inducible nitric oxide synthase production in periodontal disease.

BACKGROUND: Inducible nitric oxide synthase (iNOS) is associated with inflammation and osteoclastic differentiation in periodontal disease. This study was conducted to compare the time-dependent variation in iNOS production between the gingiva and other periodontal tissues and to explore the potential association with C-reactive protein (CRP) in early periodontal disease. METHODS: Ligature-induced periodontal disease models (0-14 days) were established in wild-type and CRP knockout rats. Changes in CRP, iNOS, and autophagy levels were examined in the gingiva and other periodontal tissues. Macrophages were treated with lipopolysaccharide and chloroquine to explore the role of autophagy in iNOS production. iNOS, CRP, and autophagy-related proteins were analyzed using Western blotting, immunostaining, and enzyme-linked immunosorbent assays. mRNA expression was detected by quantitative real-time polymerase chain reaction. Hematoxylin and eosin staining was used for histological analysis. Cathepsin K immunostaining and microcomputed tomography of the maxillae were performed to compare alveolar bone resorption. RESULTS: iNOS and CRP levels increased rapidly in periodontal tissues, as observed on Day 2 of ligature, then decreased more rapidly in the gingiva than in other periodontal tissues. CRP deficiency did not prevent iNOS generation, but effectively accelerated iNOS reduction and delayed alveolar bone loss. The CRP effect on iNOS was accompanied by a change in autophagy, which was reduced by CRP knockout. CONCLUSIONS: The regulation of iNOS by CRP shows temporospatial variation in early periodontal disease and is potentially associated with autophagy. These findings may contribute to the early detection and targeted treatment of periodontal disease.

As a potential predictor of pan-cancer, UBE2S is related to tumor-associated macrophage infiltration.

Background: At the pan-cancer level, exploring the expression and prognostic significance of a gene, such as UBE2S, will help to gain insight into the role of the gene and its feasibility for cancer screening, prognosis assessment and even gene therapy. Methods: The Cancer Genome Atlas, Human Protein Atlas, Kaplan-Meier, Tumor Immunology Estimation Resource and other databases were used to analyze the expression of UBE2S at the pan-cancer level, its prognosis and the role of the immune microenvironment. Immunohistochemistry samples of tumor tissue collected in our clinic were taken as verification. Results: UBE2S is significantly overexpressed in pan-cancer and is closely associated with malignant clinical features, poor prognosis and tumor-associated macrophages. Conclusion: UBE2S may be a potential diagnostic and prognostic marker for pan-cancer and is associated with tumor-associated macrophages.

Mechanical loading and autophagy: A study on the BoNT-A injection-induced condylar cartilage degeneration.

Botulinum toxin A (BoNT-A) has emerged as a treatment option for temporomandibular disorder (TMD). By injecting BoNT-A into the masseter muscle, it is possible to reduce mechanical loading on the temporomandibular joint (TMJ). However, numerous prior studies have indicated excessive reduction in mechanical loading can have detrimental effects on TMJ cartilage. This study proposes that autophagy, a process influenced by mechanical loading, could play a role in BoNT-A-induced mandibular condyle cartilage degeneration. To explore this hypothesis, we employed both BoNT-A injection and an excessive biting model to induce variations in mechanical loading on the condyle cartilage of C57BL/6 mice, thereby simulating an increase and decrease in mechanical loading, respectively. Results showed a significant reduction in cartilage thickness and downregulation of Runt-related transcription factor 2 (Runx2) expression in chondrocytes following BoNT-A injection. In vitro experiments demonstrated that the reduction of Runx2 expression in chondrocytes is associated with autophagy, possibly dependent on decreased YAP expression induced by low mechanical loading. This study reveals the potential involvement of the YAP/LC3/Runx2 signaling pathway in BoNT-A mediated mandibular condylar cartilage degeneration.

Activation and induction of antigen-specific T follicular helper cells play a critical role in recombinant SARS-CoV-2 RBD vaccine-induced humoral responses.

The role of follicular T helper (Tfh) cells in humoral response has been considered essential in recent years. Understanding how Tfh cells control complex humoral immunity is critical to developing strategies to improve the efficacy of vaccines against SARS-CoV-2 and other emerging pathogens. However, the immunologic mechanism of Tfh cells in SARS-CoV-2 receptor binding domain (RBD) vaccine strategy is limited. In this study, we expressed and purified recombinant SARS-CoV-2 RBD protein in Drosophila S2 cells for the first time and explored the mechanism of Tfh cells induced by RBD vaccine in humoral immune response. We mapped the dynamic of Tfh cell in lymph node and spleen following RBD vaccination and revealed the relationship between Tfh cells and humoral immune response induced by SARS-CoV-2 RBD vaccine through correlation analysis, blocking of IL-21 signaling pathway, and co-culture of Tfh with memory B cells. Recombinant RBD protein elicited a predominant Tfh1 and Tfh1-17 subset response and strong GC responses in spleen and lymph nodes, especially to enhanced vaccination. IL-21 secreted by Tfh cells affected the development and differentiation of B cells and played a key role in the humoral immune response. These observations will help us further understand the mechanism of protective immune response induced by COVID-19 vaccine and has guiding significance for the development of vaccines against newly emerging mutants.

Role of SiPHR1 in the Response to Low Phosphate in Foxtail Millet via Comparative Transcriptomic and Co-Expression Network Analyses.

Enhancing the absorption and utilization of phosphorus by crops is an important aim for ensuring food security worldwide. However, the gene regulatory network underlying phosphorus use in foxtail millet remains unclear. In this study, the molecular mechanism underlying low-phosphorus (LP) responsiveness in foxtail millet was evaluated using a comparative transcriptome analysis. LP reduced the chlorophyll content in shoots, increased the anthocyanin content in roots, and up-regulated purple acid phosphatase and phytase activities as well as antioxidant systems (CAT, POD, and SOD). Finally, 13 differentially expressed genes related to LP response were identified and verified using transcriptomic data and qRT-PCR. Two gene co-expression network modules related to phosphorus responsiveness were positively correlated with POD, CAT, and PAPs. Of these, SiPHR1, functionally annotated as PHOSPHATE STARVATION RESPONSE 1, was identified as an MYB transcription factor related to phosphate responsiveness. SiPHR1 overexpression in Arabidopsis significantly modified the root architecture. LP stress caused cellular, physiological, and phenotypic changes in seedlings. SiPHR1 functioned as a positive regulator by activating downstream genes related to LP tolerance. These results improve our understanding of the molecular mechanism underlying responsiveness to LP stress, thereby laying a theoretical foundation for the genetic modification and breeding of new LP-tolerant foxtail millet varieties.

Revealing Trade Potential for Reversing Regional Freshwater Boundary Exceedance.

Applying the planetary boundary for the freshwater framework at the regional level is important in supporting local water management but is subject to substantial uncertainty. Previous estimates have not fully investigated the potential of trade in mitigating regional freshwater boundary (RFB) exceedance. Here, we estimate RFB based on the average results of 15 different hydrological models to reduce uncertainty. We then propose a framework to divide the RFB exceedance/maintenance into contributions from both consumption and trade and further identify trade contribution into six types. We applied the framework to China's provinces, which are characterized by intensive interprovincial trade and a significant mismatch in water resource supply and demand. We found that the current trade pattern limits the role of trade to mitigate RFB exceedance. For the importing provinces exceeding RFBs, 78% of their imported goods and services came from other RFB exceeding provinces. Scenario analysis showed that relying on increased imports alone, even to its greatest extent, will not reverse RFB exceedance in most importing provinces. Increased imports, however, will have an aggregate effect on the trade partners, leading to the exceedance of the national freshwater boundary. We also found that promoting export of goods and services from non-RFB exceeding provinces and reducing their water intensity will help address the imbalance both locally and, in the aggregate, nationally.

Ultrasound-guided stellate ganglion block for the treatment of migraine in elderly patients: A retrospective and observational study.

OBJECTIVES: This study aimed to assess the effectiveness and safety of ultrasound-guided stellate ganglion block (SGB) in the prophylactic treatment of migraine in the elderly. BACKGROUND: Treatment of migraine in the elderly is often difficult and troublesome due to multiple comorbidities, drug interactions, and adverse effects (AEs). SGB may be an effective treatment approach for migraine in the elderly as its clinical use is rarely limited by concomitant diseases and age-related physiological changes; however, no studies have evaluated the effectiveness of SGB in the treatment of migraine in the elderly population. METHODS: This is a retrospective observational case series study. We retrospectively analyzed patients with migraine aged ≥65 years, who underwent ultrasound-guided SGB for headache management between January 2018 and November 2022. Pain intensity using the numerical rating scale (NRS, 0-10), number of days with headache per month, duration of headache, and the consumptions of acute medications were recorded before SGB treatment, and at 1, 2, and 3 months after the last SGB. Safety assessment included thorough documentation of serious and minor AEs related to SGB. RESULTS: Of 71 patients, 52 were analyzed in this study. After the final SGB, the NRS scores decreased significantly from a mean (± standard deviation [SD]) of 7.3 (1.2) at baseline to 3.3 (1.4), 3.1 (1.6), and 3.6 (1.6) at 1, 2, and 3 months, respectively (vs. baseline, p < 0.001). The mean (SD) number of headache days per month significantly reduced from 23.1 (5.5) to 10.9 (7.1) (p < 0.001), 12.7 (6.5) (p = 0.001), and 14.0 (6.8) days (p = 0.001) at the 1-, 2-, and 3-month follow-ups, respectively. The values of headache duration were also significantly lower at the 1-month (mean [SD] 12.5 [15.8] h, p = 0.001), 2-month (mean [SD] 11.3 [15.9] h, p = 0.001), and 3-month follow-ups (mean [SD] 14.3 [16.0] h, p = 0.001) compared to pre-treatment baseline (mean [SD] 22.7 [17.1] h). There were 33/52 (64%) patients experiencing at least a 50% reduction in acute medications consumption 3 months after the final SGB treatment. The overall AEs rate associated with ultrasound-guided SGB was 9.0% (26/290 SGBs). There were no serious AEs; all reported AEs were minor and transient. CONCLUSIONS: Stellate ganglion block treatment could reduce pain intensity, headache frequency, and duration of migraine, thereby reducing the need for adjunctive medications in elderly patients. Ultrasound-guided SGB might be a safe and effective intervention for the treatment of migraine in elderly patients.