Yorkie negatively regulates the Crustin expression during molting in Chinese mitten crab, Eriocheir sinensis.

Molting is a key biological process of crustaceans, which is mainly regulated by 20-hydroxyecdyone (20E). The molting cycle could be divided into three main stages including pre-molt, post-molt and inter-molt stages. The mechanism of immune regulation during molting process still requires further exploration. Yorkie (Yki) is a pivotal transcription factor in the Hippo signaling pathway, and it plays an essential role in regulating cell growth and immune response. In the present study, a Yki gene was identified from Eriocheir sinensis (designed as EsYki), and the regulatory role of EsYki in controlling the expression of antimicrobial peptide genes throughout the molting process was investigated. The mRNA expression level of EsYki was higher at the pre-molt stage compared to the post-molt stage and inter-molt stage. Following the injection of 20E, there was a notable and consistent rise in the EsYki mRNA expression in haemocytes. The increase was observed from 3 h to 48 h with the maximum level at 12 h. And the phosphorylation of Yki in the haemocytes was also significantly up-regulated at 3 h post 20E injection. Moreover, the levels of EsYki mRNA expression at three molting stages were significantly increased post Aeromonas hydrophila stimulation. The maximum level was detected at post-molt stage following A. hydrophila stimulation, while the lowest level was observed at inter-molt stage. The expression pattern of EsCrus was in contrast to EsCrus. After EsYki mRNA transcripts were inhibited by Yki inhibitor (CA3), the mRNA expression levels of EsCrus1 and EsCrus2 following A. hydrophila stimulation were significantly elevated. Furthermore, the phosphorylation level of NF-κB was also increased following the inhibition of Yki. Collectively, our findings indicated that EsYki could be induced by 20E and has a suppressive effect on the expression of EsCrus via inhibiting NF-κB during molting process. This research contributes to the understanding of the immunological regulation mechanism during molting process in crustaceans.

The involvement of tumor necrosis factor receptor-associated factor 6 in regulating immune response by NF-κB at pre-molt stage of Chinese mitten crab (Eriocheir sinensis).

Molting is a crucial biological process of crustaceans. Crustaceans go through three separate stages throughout their molting process, including pre-molt, post-molt and inter-molt. However, the exact mechanism of immunological modulation during molting remains unclear. Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been extensively documented to participate in immune defense. In the present study, a TRAF6 gene with two TRAF-type zinc finger domains was identified from Eriocheir sinensis (designed as EsTRAF6), and its role in regulating immune response during molting process was explored. The mRNA expression level of EsTRAF6 at pre-molt stage was higher than that at post-molt stage and inter-molt stage. After Aeromonas hydrophila stimulation, the expression levels of EsTRAF6, EsRelish and anti-lipopolysaccharide factors (ALFs) genes exhibited a considerable increase at three molting stages. Subsequently, the expression patterns of EsTRAF6 and EsRelish in response to the treatment with 20-hydroxyecdysone (20E) were examined. The mRNA expression of EsTRAF6 and EsRelish were significantly increased at 12 h after 20E injection. Additionally, the protein expression level of TRAF6 was also up-regulated in 20E group compared to control group. Furthermore, the role of EsTRAF6 in regulating the anti- ALFs expression at pre-molt stage post A. hydrophila stimulation was investigated. Following the inhibition of the EsTRAF6 transcript using RNAi or the injection of inhibitor (TMBPS), there was a notable decrease of the EsALF1, EsALF2 and EsALF3 transcripts. Moreover, a significant reduction in the phosphorylation level of NF-κB at pre-molt stage was observed after A. hydrophila stimulation in TRAF6-inhibited crabs. Collectively, our results suggest that EsTRAF6 could be induced by 20E and promoted the EsALFs expression by activating NF-κB at pre-molt stage, which providing a novel insight into the research of immune regulatory mechanism during the process of molting of crustaceans.

The impact of surgical intervention on peripheral blood T lymphocyte subsets and natural killer cell activity in pediatric obstructive sleep apnea hypopnea syndrome (OSAHS).

OBJECTIVE: This study aimed to investigate the impact of surgical intervention on peripheral blood T lymphocyte subsets and natural killer (NK) cell activity in pediatric patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: A total of 36 OSAHS children, 32 children with tonsillar hypertrophy, and 30 healthy children were enrolled. Clinical data and polysomnography (PSG) results were collected. Peripheral blood samples were analyzed for T lymphocyte subsets, NK cells, and cytokine levels including Th1 (IFN-γ, IL-2, TNF-α), Th2 (IL-4, IL-10), and Th17 (IL-17). RESULTS: At baseline, OSAHS children exhibited lower LSaO2 levels and higher AHI values compared to healthy children. They also showed decreased percentages of CD3 + T cells, CD4 + T cells, NK cells, and elevated CD8 + T cells and CD4+/CD8 + ratio. Levels of IFN-γ, IL-2, TNF-α, IL-4, and IL-17 were significantly lower in OSAHS children. Post-surgery improvements were observed in LSaO2, AHI, and immune markers at 3 months and 6 months. Pearson's correlation analysis revealed significant associations between LSaO2, AHI, and peripheral blood immune parameters at baseline and 6 months post-surgery. CONCLUSION: Surgical intervention in pediatric OSAHS influences peripheral blood T lymphocyte subsets and NK cell activity. Early intervention and monitoring of immune function are crucial for the recovery and healthy development of affected children.

lncRNA FLJ20021 regulates CDK1-mediated PANoptosis in a ZBP1-dependent manner to increase the sensitivity of laryngeal cancer-resistant cells to cisplatin.

In this study, we investigated the role of the newly discovered lncRNA FLJ20021 in laryngeal cancer (LC) and its resistance to cisplatin treatment. We initially observed elevated lncRNA FLJ20021 levels in cisplatin-resistant LC cells (Hep-2/R). To explore its function, we transfected lncRNA FLJ20021 and cyclin-dependent kinase 1 (CDK1) into Hep-2/R cells, assessing their impact on cisplatin sensitivity and PANoptosis. Silencing lncRNA FLJ20021 effectively reduced cisplatin resistance and induced PANoptosis in Hep-2/R cells. Mechanistically, lncRNA FLJ20021 primarily localized in the nucleus and interacted with CDK1 mRNA, thereby enhancing its transcriptional stability. CDK1, in turn, promoted panapoptosis in a ZBP1-dependent manner, which helped overcome cisplatin resistance in Hep-2/R cells. This study suggests that targeting lncRNA FLJ20021 can be a promising approach to combat cisplatin resistance in laryngeal cancer by regulating CDK1 and promoting PANoptosis via the ZBP1 pathway. These findings open up possibilities for lncRNA-based therapies in the context of laryngeal cancer.

Glutathione-activated biotin-targeted dual-modal imaging probe with improved PDT/PTT synergistic therapy.

BACKGROUND: Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. RESULTS: In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. SIGNIFICANCE: A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.

A Tumor-Targeting Dual-Modal imaging probe for nitroreductase in vivo.

Nitroreductase (NTR) overexpression often occurs in tumors, highlighting the significance of effective NTR detection. Despite the utilization of various optical methods for this purpose, the absence of an efficient tumor-targeting optical probe for NTR detection remains a challenge. In this research, a novel tumor-targeting probe (Cy-Bio-NO2) is developed to perform dual-modal NTR detection using near-infrared fluorescence and photoacoustic techniques. This probe exhibits exceptional sensitivity and selectivity to NTR. Upon the reaction with NTR, Cy-Bio-NO2 demonstrates a distinct fluorescence "off-on" response at 800 nm, with an impressive detection limit of 12 ng/mL. Furthermore, the probe shows on-off photoacoustic signal with NTR. Cy-Bio-NO2 has been successfully employed for dual-modal NTR detection in living cells, specifically targeting biotin receptor-positive cancer cells for imaging purposes. Notably, this probe effectively detects tumor hypoxia through dual-modal imaging in tumor-bearing mice. The strategy of biotin incorporation markedly enhances the probe's tumor-targeting capability, facilitating its engagement in dual-modal imaging at tumor sites. This imaging capacity holds substantial promise as an accurate tool for cancer diagnosis.

Discovery of the novel KIR2DL3*00111 allele in a Chinese Han individual.

The novel KIR2DL3*00111 allele differs from the closest allele KIR2DL3*00101 by a single silent mutation.

The novel KIR2DL3*037 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

The novel KIR2DL3*037 allele differs from the closest allele KIR2DL3*00101 by a single missense mutation.

BioInstruct: instruction tuning of large language models for biomedical natural language processing.

OBJECTIVES: To enhance the performance of large language models (LLMs) in biomedical natural language processing (BioNLP) by introducing a domain-specific instruction dataset and examining its impact when combined with multi-task learning principles. MATERIALS AND METHODS: We created the BioInstruct, comprising 25 005 instructions to instruction-tune LLMs (LLaMA 1 and 2, 7B and 13B version). The instructions were created by prompting the GPT-4 language model with 3-seed samples randomly drawn from an 80 human curated instructions. We employed Low-Rank Adaptation (LoRA) for parameter-efficient fine-tuning. We then evaluated these instruction-tuned LLMs on several BioNLP tasks, which can be grouped into 3 major categories: question answering (QA), information extraction (IE), and text generation (GEN). We also examined whether categories (eg, QA, IE, and generation) of instructions impact model performance. RESULTS AND DISCUSSION: Comparing with LLMs without instruction-tuned, our instruction-tuned LLMs demonstrated marked performance gains: 17.3% in QA on average accuracy metric, 5.7% in IE on average F1 metric, and 96% in Generation tasks on average GPT-4 score metric. Our 7B-parameter instruction-tuned LLaMA 1 model was competitive or even surpassed other LLMs in the biomedical domain that were also fine-tuned from LLaMA 1 with vast domain-specific data or a variety of tasks. Our results also show that the performance gain is significantly higher when instruction fine-tuning is conducted with closely related tasks. Our findings align with the observations of multi-task learning, suggesting the synergies between 2 tasks. CONCLUSION: The BioInstruct dataset serves as a valuable resource and instruction tuned LLMs lead to the best performing BioNLP applications.

Lanthanum-modified pyroaurite as a geoengineering tool to simultaneously sink Microcystis cyanobacteria and immobilize phosphorus in eutrophic water.

Excessive phosphorus (P) in eutrophic water induces cyanobacterial blooms that aggravate the burden of in-situ remediation measures. In order to ensure better ecological recovery, Flock & Lock technique has been developed to simultaneously sink cyanobacteria and immobilize P but requires a combination of flocculent and P inactivation agent. Here we synthesized a novel lanthanum-modified pyroaurite (LMP), as an alternative for Flock & Lock of cyanobacteria and phosphorus at the background of rich humic acid and suspended solids. LMP shows a P adsorption capacity of 36.0 mg/g and nearly 100 % removal of chlorophyll-a (Chl-a), turbidity, UV254 and P at a dosage (0.3 g/L) much lower than the commercial analogue (0.5 g/L). The resultant sediment (98.2 % as immobile P) exhibits sound stability without observable release of P or re-growth of cyanobacteria over a 50-day incubation period. The use of LMP also constrains the release of toxic microcystins to 1.4 µg/L from the sunk cyanobacterial cells, outperforming the commonly used polyaluminum chloride (PAC). Similar Flock & Lock efficiency could also be achieved in real eutrophic water. The outstanding Flock & Lock performance of LMP is attributable to the designed La modification. During LMP treatment, La acts as not only a P binder by formation of LaPO4, but also a coagulant to create a synergistic effect with pyroaurite. The controlled hydrolysis of surface La(III) over pyroaurite aided the possible formation of La(III)-pyroaurite networking structure, which significantly enhanced the Flock & Lock process through adsorption, charge neutralization, sweep flocculation and entrapment. In the end, the preliminary economic analysis is performed. The results demonstrate that LMP is a versatile and cost-effective agent for in-situ remediation of eutrophic waters.

Carbon redirection via tunable Fenton-like reactions under nanoconfinement toward sustainable water treatment.

The ongoing pattern shift in water treatment from pollution control to energy recovery challenges the energy-intensive chemical oxidation processes that have been developed for over a century. Redirecting the pathways of carbon evolution from molecular fragmentation to polymerization is critical for energy harvesting during chemical oxidation, yet the regulation means remain to be exploited. Herein, by confining the widely-studied oxidation system-Mn3O4 catalytic activation of peroxymonosulfate-inside amorphous carbon nanotubes (ACNTs), we demonstrate that the pathways of contaminant conversion can be readily modulated by spatial nanoconfinement. Reducing the pore size of ACNTs from 120 to 20 nm monotonously improves the pathway selectivity toward oligomers, with the yield one order of magnitude higher under 20-nm nanoconfinement than in bulk. The interactions of Mn3O4 with ACNTs, reactant enrichment, and pH lowering under nanoconfinement are evidenced to collectively account for the enhanced selectivity toward polymerization. This work provides an adaptive paradigm for carbon redirection in a variety of catalytic oxidation processes toward energy harvesting and sustainable water purification.

Activating transcription factor 3 is a new biomarker correlation with renal clear cell carcinoma progression.

Background: Clear cell renal cell carcinoma (ccRCC) is the most invasive type of cancer, with a high risk of metastasis and recurrence. Therefore, there is an urgent need to identify novel prognostic predictors and therapeutic targets of ccRCC. Activating transcription factor 3 (ATF3), a tumor oncogene or repressor, has rarely been examined in ccRCC. In the present study, we comprehensively elucidate the prognostic value and potential functions of ATF3 in ccRCC.Methods: Several TCGA-based online databases were used to analyze ATF3 expression in ccRCC and determine ccRCC prognosis. The upstream-binding micro (mi) RNAs of ATF3 and long non-coding (lnc)RNAs were predicted using the StarBase database.Results: Analysis of several TCGA-based online databases showed that ATF3 expression is decreased in ccRCC, suggesting a significant association with the prognosis of patients with ccRCC. Furthermore, we found hsa-miR-221-3p to be potential regulatory miRNA of ATF3 in ccRCC. Prediction and analysis of the upstream lncRNAs indicated that PAXIP1-AS2 and OIP5-AS1 were the most potent upstream lncRNAs of the hsa-miR-221-3p/ATF3 axis in ccRCC. The results of the GO and KEGG analyses implied that ATF3 is likely involved in the regulation of apoptotic signaling in response to endoplasmic reticulum (ER) stress in ccRCC. Correlation analysis revealed a positive relationship between ATF3 expression and ER stress.Conclusions: Our in silico findings highlighted that ATF3 expression was low in ccRCC and negatively correlated with poor prognosis. Furthermore, PAXIP1-AS2 and the OIP5-AS1/hsa-miR-221-3p/ATF3 axis were identified as significant potential regulators of ER stress-mediated apoptosis in ccRCC.

Oxidation of emerging contaminants by S(IV) activated ferrate: Identification of reactive species.

Studies on the Fe(VI)/S(IV) process have focused on improving the efficiency of emerging contaminants (ECs) degradation under alkaline conditions. However, the performance and mechanisms under varying pH levels remain insufficiently investigated. This tudy delved into the efficiency and mechanism of Fe(VI)/S(IV) process using sulfamethoxazole (SMX) and ibuprofen (IBU) as model contaminants. We found that pH was crucial in governing the generation of reactive species, and both Fe(V/IV) and SO4•- were identified in the reaction system. Specifically, an increase in pH favored the formation of SO4•-, while the formation of Fe(VI) to Fe(V/IV) became more significant at lower pH. At pH 3.2, Fe(III) resulting from the Fe(VI) self-decay reactedwith HSO3-to produce SO4•-and •OH. Under near-neutral conditions, the coexistance of Fe(V/IV) and SO4•- in abundance contributed to the optimal oxidation of both pollutants in the Fe(VI)/S(IV) process, with the removal exceeding 74% in 5 min. Competitive quenching experiments showed that the contributions of Fe(V/IV) to SMX and IBU destruction dimished, while the contributions of radicals increased with an increase in pH. However, this evolution was slower during SMX degradation compared to IBU degradation. A comprehensive understnding of pH as the key factor is essential for the optimization of the sulfite-activated Fe(VI) oxidation process in water treatment.

Fabrication of antimicrobial PCL/EC nanofibrous films containing natamycin and trans-cinnamic acid by microfluidic blow spinning for fruit preservation.

Fruit is susceptible to various postharvest pathogens; thus, the development of multifunctional preservation materials that can achieve the broad-spectrum inhibition of different pathogens is a current research hotspot. Here, microfluidic blow spinning was used to create a biodegradable polycaprolactone/ethyl cellulose (PCL/EC) nanofibrous film that incorporated two naturally-sourced compounds, natamycin and trans-cinnamic acid, resulting in multi-microbial inhibition. The PCL/EC-based film had a smooth and even morphology, indicating the favorable integration of PCL and EC. After the incorporation of ingredients, the film exhibited good inhibitory activity against Escherichia coli, Staphylococcus aureus, and Botrytis cinerea, and it had finer fiber diameters, higher permeability, and antioxidant properties. We further demonstrated that strawberries that were padded with the film had good resistance to Botrytis cinerea. Also, the film did not interference with the qualities of the strawberries during storage. The study demonstrates a promising application for multi-antimicrobial and bio-friendly packaging materials in postharvest fruit preservation.

Mechanisms of the response of apple fruit to postharvest compression damage analyzed by integrated transcriptome and metabolome.

Apple fruit is susceptible to compression damage within the postharvest supply chain given its thin peels and brittle texture, which can result in decay and deterioration and have a substantial impact on its marketability and competitiveness. Thorough bioinformatics investigations are lacking on postharvest compression damage stress-induced alterations in genes and metabolic regulatory networks in fruits. In the present study, a comprehensive analysis of both the transcriptome and metabolome was conducted on 'Red Fuji' apples experiencing compression-induced damage. During the storage after damage has occurred, the gene expression of MdOFUT19, MdWRKY48, MdCBP60E, MdCYP450 and MdSM-like of the damaged apples was consistently higher than that of the control group. The damaged apples also had higher contents of some metabolites such as procyanidin A1, Dl-2-Aminooctanoic acid, 5-O-p-Coumaroyl shikimic acid and 5,7-Dihydroxy-3',4',5'-trimethoxyflavone. Analysis of genes and metabolites with distinct expressions on the common annotation pathway suggested that the fruit may respond to compression stress by promoting volatile ester and lignin synthesis. The above results can deepen the comprehension of the response mechanisms in apple fruits undergoing compression-induced damage.

Associations of dichlorophenol with metabolic syndrome based on multivariate-adjusted logistic regression: a U.S. nationwide population-based study 2003-2016.

BACKGROUND: Para-dichlorobenzene (p-DCB) exposure associated with oxidative stress has indeed raised public concerns. However, whether p-DCB is linked with metabolic syndrome (MetS) remains unclear. We hypothesized that higher exposure to p-DCB would be linked with a higher risk of MetS in the U.S population. This study aimed to examine the associations of exposure to p-DCB with MetS prevalence. METHODS: We included 10,428 participants (5,084 men and 5,344 women), aged ≥ 20 years, from the National Health and Nutrition Examination Survey (2003-2016). The cases of MetS were diagnosed by NCEP/ATPIII. Logistic regression models were conducted to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of MetS prevalence. Moreover, the mix associations of p-DCB metabolites were assessed using quantile sum (WQS) regression and quantile g-computation (qgcomp) methods. RESULTS: We documented 2,861 (27.1%) MetS cases. After adjustment for the potential risk factors, the ORs (95% CI) of MetS prevalence across the quartile of urinary 2,5-dichlorophenol (2,5-DCP) were 1.09 (0.93-1.28), 1.22 (1.00-1.49), and 1.34 (1.04-1.73). Moreover, 2,5 DCP is significantly associated with a higher prevalence of abdominal obesity [ORQ4vsQ1 (95% CI): 1.23 (1.03-1.48)]. The WQS and qgcomp index also showed significant associations between p-DCB metabolites and MetS. Moreover, we further examined that 2,5 DCP was correlated with higher systolic blood pressure (r = 0.022, P = 0.027), waist circumference (r = 0.099, P < 0.001), and glycohemoglobin (r = 0.027, P = 0.008) and a lower high density cholesterol (r = -0.059, P < 0.001). In addition, the significant positive associations between 2,5 DCP and MetS were robust in the subgroup and sensitivity analyses. CONCLUSION: These findings indicated that increased urinary p-DCB concentration, especially 2,5 DCP, had a higher MetS prevalence. These results should be interpreted cautiously and further research is warranted to validate our findings.

Polarized upconversion emission at metasurface.

Leveraging the resonant modes of all-dielectric metasurfaces, specifically quasi-bound state in the continuum and Mie resonances, the precise orthogonal polarization control has been realized.

Lonicera caerulea L. polyphenols improve short-chain fatty acid levels by reshaping the microbial structure of fermented feces in vitro.

Increasing evidence suggests that the pathogenesis of type 2 diabetes mellitus (T2DM) is closely related to the gut microbiota. Polyphenols have been shown to alleviate T2DM, but the effects of L. caerulea L. polyphenols (LPs) on the gut microbiota and metabolites remain elusive. In this study, the inhibitory effects of fermented L. caerulea L. polyphenols (FLPs) and unfermented L. caerulea L. polyphenols (ULPs) on α-amylase and α-glucosidase and the impact of LP on the gut microbiota and metabolites were investigated. Furthermore, the relationship between the two was revealed through correlation analysis. The results showed that ULP and FLP had the highest inhibitory rates against α-amylase and α-glucosidase at 4 mg ml-1, indicating a strong inhibitory ability. In addition, LP plays a regulatory role in the concentration of short-chain fatty acids (SCFAs) and tends to restore them to their normal levels. LP reversed the dysbiosis of the gut microbiota caused by T2DM, as evidenced by an increase in the abundance of bacterial genera such as Lactobacillus, Blautia, and Bacteroides and a decrease in the abundance of bacterial genera such as Escherichia-Shigella and Streptococcus. Similarly, after LP intervention, the relationships among microbial species became more complex and interconnected. In addition, the correlation between the gut microbiota and metabolites was established through correlation analysis. These further findings clarify the mechanism of action of LP against T2DM and provide a new target for T2DM interventions.

Clinical value of glucocorticoids for severe community-acquired pneumonia: A systematic review and meta-analysis based on randomized controlled trials.

BACKGROUND: Severe community-acquired pneumonia (sCAP) is characterized by severe symptoms and a poor prognosis, especially with the recent global impact of novel coronavirus in recent years. The use of glucocorticoids in sCAP is currently a subject of debate. To evaluate the clinical efficacy and safety of glucocorticoids and provide guidance for their rational use in clinical practice, we conducted this study. METHODS: We searched PubMed, Web of Science, and China National Knowledge Infrastructure using the following search terms: "pneumonia", "pneumonias", "Pulmonary Inflammation", "Pulmonary Inflammations", "Lung Inflammation", and "Lung Inflammations". The primary outcomes included mortality and the length of hospital stay. The secondary outcomes included the duration of mechanical ventilation, duration of vasoactive drug use, gastrointestinal bleeding, and multiple infections. The Cochrane Collaboration was used to assess the risk of bias of the included studies. Stata/MP14 was used for meta-analysis. RESULTS: These studies contained information on 1252 patients who received glucocorticoids and 1280 patients who did not. Meta-analysis showed that there was no difference in terms of mortality [risk ratio (RR) = 0.93, 95% confidence interval (CI): 0.81-1.07, P  > .05], gastrointestinal bleeding (RR = 1.38, 95% CI: 0.83-2.30, P  <  .05), multiple infections (RR = 1.17, 95% CI: 0.90-1.53, P  > .05) and length of hospital stay (mean difference [MD] = -0.87, 95% CI: -2.35 to 0.61, P  > .05) between the hormonal and nonhormonal groups. However, there was a significant difference in the duration of mechanical ventilation (MD = -1.54; 95% CI, -1.89 to -1.12, P  <  .05) and the duration of use of vasoactive drugs (MD = -14.09, 95% CI: -15.72 to -12.46, P < .05). CONCLUSION: Glucocorticoids reduced the duration of mechanical ventilation duration and vasoactive drug use in sCAP patients without increasing the risk of adverse events including hyperglycemia and multiple infections. However, there was no significant difference in mortality or length of hospital stay in sCAP patients between glucocorticoid and non-glucocorticoid groups. Glucocorticoids could be recommended for patients with sCAP with respiratory failure or hemodynamic instability.

TransformEHR: transformer-based encoder-decoder generative model to enhance prediction of disease outcomes using electronic health records.

Deep learning transformer-based models using longitudinal electronic health records (EHRs) have shown a great success in prediction of clinical diseases or outcomes. Pretraining on a large dataset can help such models map the input space better and boost their performance on relevant tasks through finetuning with limited data. In this study, we present TransformEHR, a generative encoder-decoder model with transformer that is pretrained using a new pretraining objective-predicting all diseases and outcomes of a patient at a future visit from previous visits. TransformEHR's encoder-decoder framework, paired with the novel pretraining objective, helps it achieve the new state-of-the-art performance on multiple clinical prediction tasks. Comparing with the previous model, TransformEHR improves area under the precision-recall curve by 2% (p < 0.001) for pancreatic cancer onset and by 24% (p = 0.007) for intentional self-harm in patients with post-traumatic stress disorder. The high performance in predicting intentional self-harm shows the potential of TransformEHR in building effective clinical intervention systems. TransformEHR is also generalizable and can be easily finetuned for clinical prediction tasks with limited data.