Glucose activated synergistic cascade therapy of diabetic wound by platinum and glucose oxidase decorated camelina lipid droplets.

Hyperglycemia provides a favorable breeding ground for bacteria, resulting in repeated and persistent inflammation of wounds and prolonged healing processes. In this study, platinum (Pt) nanoparticles (NPs) and glucose oxidase (GOx) were decorated on the surface of camelina lipid droplets (OB) linked with hFGF2, forming PGOB through in situ reduction of Pt ions and electrostatic adsorption, respectively. PGOB exhibits cascade enzyme catalytic activity, which can be activated by glucose in diabetic wound tissues. Specifically, GOx on PGOB catalyzes glucose into hydrogen peroxide, which can further decompose into hydroxyl radicals that have higher toxicity for bacterial inactivation. Additionally, glucose decomposition creates a low pH microenvironment, facilitating the cascade catalytic activity that ensures better bacterial suppression within the wound tissues. Furthermore, hFGF2 promotes the proliferation and migration of fibroblasts. Both in vitro and in vivo experiments confirm that PGOB effectively accelerates wound healing processes through bacteria inactivation and tissue regeneration. This study has developed an alternative strategy for glucose-triggered synergistic cascade therapy for diabetic wounds.

Erratum: Corrigendum: Liu W-B, Wang C-Y, Tang Y-N, Wang Y, Pei W-X, Yan C-C (2024) Six new species of Cryptochironomus Kieffer (Diptera, Chironomidae) from the Nearctic region. ZooKeys 1200: 275-302. doi: 10.3897/zookeys.1200.119225.

[This corrects the article DOI: 10.3897/zookeys.1200.119225.].

Stiffener and staggered-square honeycomb structure design for lobster eye x ray micro pore optics.

Lobster eye x ray micro pore optics (MPO) is a novel bionic optical technology with a unique microchannel structure. All square microchannels point to the same spherical center position, providing a wide field of view and high focusing and imaging capabilities. Enhancing the optical performance of MPO has been a significant challenge. This study introduces what we believe is a novel approach using a stiffener and staggered-square honeycomb structure design to enhance the optical properties of the MPO devices. The x ray test results show that the multifiber stiffener design enhances optical quality by approximately 20% during the melt pressing stage. The staggered-square honeycomb structure design reduces channel errors by nearly 67% in the thermal forming and coating stage. Consequently, the angular resolution of the MPO has been significantly enhanced, reducing from 4.25 to 2.68 arc min. This innovative structure design shows promise for enhancing lobster eye optics performance and has potential applications in the related field.

Brain network localization of gray matter atrophy, neurocognitive and social cognitive dysfunction in schizophrenia.

BACKGROUND: Numerous studies have established the presence of gray matter atrophy and brain activation abnormalities during neurocognitive and social cognitive tasks in schizophrenia. Despite a growing consensus that diseases localize better to distributed brain networks than individual anatomical regions, there is still a dearth of literature examining brain network localization of gray matter atrophy, neurocognitive and social cognitive dysfunction in schizophrenia. METHODS: To address this gap, we initially identified brain locations of structural and functional abnormalities in schizophrenia from 301 published neuroimaging studies with 8712 schizophrenia individuals and 9275 healthy controls. By applying novel functional connectivity network mapping to large-scale resting-state functional magnetic resonance imaging datasets, we mapped these affected brain locations to 3 brain abnormality networks of schizophrenia. RESULTS: The gray matter atrophy network of schizophrenia comprised a broadly distributed set of brain areas predominantly implicating the ventral attention, somatomotor, and default networks. The neurocognitive dysfunction network was also composed of widespread brain areas primarily involving the frontoparietal and default networks. By contrast, the social cognitive dysfunction network consisted of circumscribed brain regions mainly implicating the default, subcortical, and visual networks. CONCLUSIONS: Our findings suggest shared and unique brain network substrates of gray matter atrophy, neurocognitive and social cognitive dysfunction in schizophrenia, which may not only refine the understanding of disease neuropathology from a network perspective, but also potentially contribute to more targeted and effective treatments for impairments in different cognitive domains in schizophrenia.

Aucubin suppresses TLR4/NF-κB signalling to shift macrophages toward M2 phenotype in glucocorticoid-associated osteonecrosis of the femoral head.

In this study, we investigated whether the ability of aucubin to mitigate the pathology of GONFH involves suppression of TLR4/NF-κB signalling and promotion of macrophage polarization to an M2 phenotype. In necrotic bone tissues from GONFH patients, we compared levels of pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages as well as levels of TLR4/NF-κB signalling. In a rat model of GONFH, we examined the effects of aucubin on these parameters. We further explored its mechanism of action in a cell culture model of M1 macrophages. Necrotic bone tissues from GONFH patients contained a significantly increased macrophage M1/M2 ratio, and higher levels of TLR4, MYD88 and NF-κB p65 than bone tissues from patients with hip osteoarthritis. Treating GONFH rats with aucubin mitigated bone necrosis and demineralization as well as destruction of trabecular bone and marrow in a dose-dependent manner, based on micro-computed tomography. These therapeutic effects were associated with a decrease in the overall number of macrophages, decrease in the proportion of M1 macrophages, increase in the proportion of M2 macrophages, and downregulation of TLR4, MYD88 and NF-κB p65. These effects in vivo were confirmed by treating cultures of M1 macrophage-like cells with aucubin. Aucubin mitigates bone pathology in GONFH by suppressing TLR4/NF-κB signalling to shift macrophages from a pro- to anti-inflammatory phenotype.

Preparation and characterization of agarose-sodium alginate hydrogel beads for the co-encapsulation of lycopene and resveratrol nanoemulsion.

In the study, lycopene and resveratrol nanoemulsion hydrogel beads were prepared by using agarose­sodium alginate as a carrier and the semi-interpenetrating polymer network technique, characteristics and morphologies were evaluated by scanning electron microscopy, fluorescence microscopy, rheological measurement. The synergistic antioxidant effect of lycopene and resveratrol was confirmed, the best synergistic antioxidant performance is achieved when the ratio of 1:1. To increase the solubility and improve the stability, the lycopene was prepared as solid dispersion added to the nanoemulsion. The encapsulation rate of lycopene and resveratrol reached 93.60 ± 2.94 % and 89.30 ± 1.75 %, respectively, and the cumulative release showed that the addition of agarose slowed down the release rate of the compound, which improves the applicability of lycopene and resveratrol and development of carriers for the delivery of different bioactive ingredients.

Perichondritis of the auricle: bacterial or fungal? (A case series).

BACKGROUND: Suppurative perichondritis of the auricle is a common disease that can easily cause malformations if it develops into an uncontrolled infection. In nearly half of the cases, otolaryngologists cannot identify the pathogens involved. CASE PRESENTATION: In the present work, we described two cases of pyogenic perichondritis, with negative on conventional culture. However, using metagenomic next-generation sequencing (mNGS), we detected fungal infections in the patients and after the patients were given anti-fungal treatment, the patients achieved a good prognosis. CONCLUSIONS: These cases highlighted the possibility that fungi might be the involved pathogens in patients who have had multiple negative bacterial cultures, and mNGS should be applied in these cases. mNGS could be used as a supplement to traditional culture methods.

Deep learning for multi-type infectious keratitis diagnosis: A nationwide, cross-sectional, multicenter study.

The main cause of corneal blindness worldwide is keratitis, especially the infectious form caused by bacteria, fungi, viruses, and Acanthamoeba. The key to effective management of infectious keratitis hinges on prompt and precise diagnosis. Nevertheless, the current gold standard, such as cultures of corneal scrapings, remains time-consuming and frequently yields false-negative results. Here, using 23,055 slit-lamp images collected from 12 clinical centers nationwide, this study constructed a clinically feasible deep learning system, DeepIK, that could emulate the diagnostic process of a human expert to identify and differentiate bacterial, fungal, viral, amebic, and noninfectious keratitis. DeepIK exhibited remarkable performance in internal, external, and prospective datasets (all areas under the receiver operating characteristic curves > 0.96) and outperformed three other state-of-the-art algorithms (DenseNet121, InceptionResNetV2, and Swin-Transformer). Our study indicates that DeepIK possesses the capability to assist ophthalmologists in accurately and swiftly identifying various infectious keratitis types from slit-lamp images, thereby facilitating timely and targeted treatment.

The impact of combined administration of ropivacaine and dexamethasone on postoperative analgesia in perianal surgery with pudendal nerve block under ultrasound guidance: a prospective randomized controlled study.

Background: In recent years, severe pain after perianal surgery has seriously affected the prognosis of hospitalized patients. How to maximize the improvement of postoperative pain and perioperative comfort becomes particularly important. Methods: This study was a double-blind randomized controlled trial (Registration No.: ChiCTR2100048760, Registration Date: 16 July 2021, Link: www.chictr.org.cn/showproj.html?proj=130226), and patients were randomly divided into two groups: one group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine (P group), and the other group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine + 8 mg dexamethasone (PD group). The primary outcome was the incidence of moderate to severe pain at the first postoperative dressing change. Secondary outcomes included Quality of recovery-15 (QoR-15) score at 3 days after surgery, sleep quality, pain score at 3 days after surgery, and incidence of adverse events. Results: In the main outcome indicators, the incidence was 41.7% in the P group and 24.2% in the PD group (p = 0.01). The QoR-15 score and sleep quality in PD group were better than those in P group 2 days before surgery. The incidence of postoperative urinary retention was significantly decreased in PD group (p = 0.01). Conclusion: Local anesthesia with dexamethasone combined with pudendal nerve block after perianal surgery can reduce the incidence of moderate to severe pain during the first dressing change. This may be one of the approaches to multimodal analgesia after perianal surgery. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2100048760.

Whole-Exome Sequencing Identifies Germline BLM Mutation in Ovarian Hepatoid Adenocarcinoma with Favorable Response to Niraparib and Anlotinib Combination Therapy-A Case Report and Literature Review.

Hepatoid adenocarcinoma of the ovary represents a rare and malignant extrahepatic tumor that shares morphological and immunophenotypic similarities with hepatocellular carcinoma. Due to the ambiguous histomorphology and aggressive behavior, the diagnosis and management of hepatoid adenocarcinoma of the ovary present unique challenges. Here, we present a 67-year-old woman with massive ascites and disseminated peritoneal implants at initial diagnosis. She was treated with six cycles of neoadjuvant therapy (albumin-bound paclitaxel + nedaplatin + bevacizumab) and a debulking surgery, followed by eight cycles of postoperative adjuvant therapy (albumin-bound paclitaxel + carboplatin + bevacizumab). Elaborate pathology workup found significant involvement of angiogenesis in the tumor and confirmed the diagnosis via immunohistochemistry. Further molecular characterization of the tumor by whole-exome sequencing (WES) revealed a novel heterozygous germline mutation (NM_000057.2, c.1290_1291delinsATCAGGCCTCCATAG, p.Y430fs1) in gene BLM, likely pathogenic, suggesting a potential candidate for Poly (ADP-ribose) polymerase (PARP) inhibitors. For the maintenance therapy, she received a combination of the PARP inhibitor niraparib and the antiangiogenic anlotinib. As of now, the patient has achieved a partial response, with no apparent evidence of disease progression observed nearly 30 months. Our study sheds light on the WES-based profiling in rare cancers to screen for any treatable targets with otherwise no standard therapeutic options. The promising results with the niraparib-anlotinib combination suggest its potential as a maintenance therapy option for hepatoid adenocarcinoma of the ovary, which warrants validation in future larger cohort.

Assessment of Non-Phytate Phosphorus Requirements of Chinese Jing Tint 6 Layer Chicks from Hatch to Day 42.

We aimed to estimate the non-phytate phosphorus (NPP) requirements of Chinese Jing Tint 6 layer chicks. We randomly allocated 720 birds to five treatments with six cages of 24 birds each, feeding them a corn-soybean diet containing 0.36%, 0.41%, 0.46%, 0.51%, and 0.56% NNP. The results showed that the body weight gain (BWG), tibial length, and apparent total tract digestibility coefficients (ATTDC) of P were affected (p < 0.05) by dietary NPP level. A quadratic broken-line analysis (p < 0.05) of BWG indicated that the optimal NPP for birds aged 1-14 d was 0.411%. Similarly, 0.409% of NPP met tibial growth needs. However, 0.394% of NPP was optimal for P utilization according to the ATTDC criterion. For 15-42 d birds, 0.466% NPP, as estimated by the BWG criterion, was sufficient for optimal growth without decreasing P utilization. Using the factorial method, NPP requirements were calculated as 0.367% and 0.439%, based on the maintenance factors and BWG for 1-14 and 15-42 d birds, respectively, to maintain normal growth. Combining the non-linear model with the factorial method, this study recommends dietary NPP levels of 0.367% and 0.439% for 1-14 and 15-42 d birds, respectively, to optimize P utilization without affecting performance.

Unlocking the Potential of Ultra-High Dose Fractionated Radiation for Effective Treatment of Glioblastoma in Mice.

Background: Current radiotherapy regimens for glioblastoma (GBM) have limited efficacy and fails to eradicate tumors. Regenerative medicine brings hope for repairing damaged tissue, opening opportunities for elevating the maximum acceptable radiation dose. In this study, we explored the effect of ultra-high dose fractionated radiation on tumor responses and brain injury in immunocompetent mice which can better mimic the tumor-host interactions observed in patients. We also evaluated the role of the hypoxia-inducible factor-1 alpha under radiation as potential target for combating radiation-induced brain injury. Methods: Naïve and Hif-1α+/- heterozygous mice received a fractionated daily dose of 20 Gy for three or five consecutive days. Magnetic resonance imaging (MRI) and histology were performed to assess brain injury post-radiation. The 2×105 human GBM1 luciferase-expressing cells were transplanted with tolerance induction protocol. Fractionated radiotherapy was performed during the exponential phase of tumor growth. Bioluminescence imaging, MRI, and immunohistochemistry staining were performed to evaluate tumor growth dynamics and radiotherapy responses. Additionally, animal lifespan was recorded. Results: Fractionated radiation of 5×20 Gy induced severe brain damage, starting 3 weeks after radiation. All animals from this group died within 12 weeks. In contrast, later onset and less severe brain injury were observed starting 12 weeks after radiation of 3×20 Gy. It resulted in complete GBM eradication and survival of all treated animals. Furthermore, Hif-1α+/- mice exhibited more severe vascular damage after fractionated radiation of 3×20 Gy. Conclusion: Ultra-high dose fractionated 3×20 Gy radiation has the potential to fully eradicate GBM cells at the cost of only mild brain injury. The Hif-1α gene is a promising target for ameliorating vascular impairment post-radiation, encouraging the implementation of neurorestorative strategies.

Impact of "3414" fertilization on the yield and quality of greenhouse tomatoes.

This study aimed to explore the effects of different nitrogen, phosphorus, and potassium ratios on the yield and nutritional quality of greenhouse tomatoes under a water and fertilizer integration model. Greenhouse tomatoes were used as the research object, and the "3414" fertilizer trial design was employed to assess tomato growth, yield, quality, and soil indicators across various treatment combinations. The goal was to determine the optimal fertilization scheme and recommend appropriate fertilizer quantities for tomato cultivation and production. The results revealed that different fertilizer ratios significantly affected both the quality and yield of tomatoes. Overall, the tomato yield tended to increase with higher fertilization amounts, with potassium exhibiting the most pronounced effect on yield increase, followed by phosphorus and nitrogen. The comprehensive analysis of principal components indicated that the N2P2K1 treatment yielded the highest nutritional quality and yield. Therefore, the best fertilization combination identified in this study consisted of nitrogen fertilizer at 197.28 kg hm-2, phosphorus fertilizer at 88.75 kg hm-2, and potassium fertilizer at 229.80 kg hm-2. These findings provided the scientific basis for optimizing fertilization practices in greenhouse tomato cultivation and production in the Jilin Province.

A novel quantitative double antigen sandwich ELISA for detecting total antibodies against Candida albicans enolase 1.

PURPOSE: This study aimed to develop a double antigen sandwich ELISA (DAgS-ELISA) method for more efficient, accurate, and quantitative detection of total antibodies against Candida albicans enolase1 (CaEno1) for diagnosing invasive candidiasis (IC). METHODS: DAgS-ELISA was developed using recombinant CaEno1 and a monoclonal antibody as the standard. Performance evaluation included limit of detection, accuracy, and repeatability. Dynamic changes in antibody levels against CaEno1 in serum from systemic candidiasis mice were analyzed using DAgS-ELISA. Patient serum samples from IC, Candida colonization, bacterial infections, and healthy controls were analyzed with DAgS-ELISA and indirect ELISA. RESULTS: DAgS-ELISA outperformed indirect ELISA in terms of linear range and test background. In systemic candidiasis mice, a distinctive 'double-peak' pattern in dynamic antibody levels was observed. Additionally, there was a high level of consistency in the positive rates of CaEno1 antibodies detected by both DAgS-ELISA and indirect ELISA. While the positivity rates differed among patient groups, no significant variations in antibody levels were detected among the various positive patient groups. CONCLUSIONS: DAgS-ELISA offers a reliable novel approach for IC diagnosis, enabling rapid, accurate, and quantitative detection of CaEno1 antibodies. Further validation and optimization are needed for its clinical application and effectiveness.

Expression and clinical significance of interleukin-10, transforming growth factor-ß1, and CD4+CD25 cytokines in paediatric allergic rhinitis with allergic asthma.

Introduction: It was intended to research the level changes and clinical significance of interleukin (IL)-10, transforming growth factor ß1 (TGF-ß1), and CD4+CD25 cytokines in paediatric allergic rhinitis (AR) accompanied with allergic asthma (AA). Material and methods: Eighty children of AA with AR receiving immunotherapy indications were included as the experimental group (EG), while another 40 healthy children in the same period were selected as the control group (CG). IL-10, TGF-ß1, and CD4+CD25 levels in cells of the two groups before and after treatment were compared and analysed. Results: The serum TGF-ß1 level was determined as 1,045.7 ±44.7 pg/ml in the EG at admission, remarkably higher than that in the CG (p < 0.05). The IL-10 level was 21.4 ±2.8 pg/ml; CD4+CD25 cells accounted for 9.2 ±2.4%, CD4+CD25high cells accounted for 0.6 ±0.3%. These were all greatly lower than those in the CG (p < 0.05). At discharge, the serum TGF-ß1 level in the EG was 903.7 ±29.4 pg/ml, which was still memorably higher than that in the CG (p < 0.05). The IL-10 level changed to 32.8 ±3.7 pg/ml; the percentage of CD4+CD25 was 11.3 ±1.8, respectively, among CD4+T cells. These were also notably lower than those in the CG at discharge (p < 0.05). Conclusions: IL-10, TGF-ß1, and CD4+CD25 level changes in cells might be of reference value as therapeutic indicators for clinical treatment or evaluation of paediatric AR with AA.

Organ-on-a-chip: future of female reproductive pathophysiological models.

The female reproductive system comprises the internal and external genitalia, which communicate through intricate endocrine pathways. Besides secreting hormones that maintain the female secondary sexual characteristics, it also produces follicles and offspring. However, the in vitro systems have been very limited in recapitulating the specific anatomy and pathophysiology of women. Organ-on-a-chip technology, based on microfluidics, can better simulate the cellular microenvironment in vivo, opening a new field for the basic and clinical research of female reproductive system diseases. This technology can not only reconstruct the organ structure but also emulate the organ function as much as possible. The precisely controlled fluidic microenvironment provided by microfluidics vividly mimics the complex endocrine hormone crosstalk among various organs of the female reproductive system, making it a powerful preclinical tool and the future of pathophysiological models of the female reproductive system. Here, we review the research on the application of organ-on-a-chip platforms in the female reproductive systems, focusing on the latest progress in developing models that reproduce the physiological functions or disease features of female reproductive organs and tissues, and highlighting the challenges and future directions in this field.

Metagenomic analysis reveals altered gut virome and diagnostic potential in pancreatic cancer.

Pancreatic cancer (PC) is a highly aggressive malignancy with a poor prognosis, making early diagnosis crucial for improving patient outcomes. While the gut microbiome, including bacteria and viruses, is believed to be essential in cancer pathogenicity, the potential contribution of the gut virome to PC remains largely unexplored. In this study, we conducted a comparative analysis of the gut viral compositional and functional profiles between PC patients and healthy controls, based on fecal metagenomes from two publicly available data sets comprising a total of 101 patients and 82 healthy controls. Our results revealed a decreasing trend in the gut virome diversity of PC patients with disease severity. We identified significant alterations in the overall viral structure of PC patients, with a meta-analysis revealing 219 viral operational taxonomic units (vOTUs) showing significant differences in relative abundance between patients and healthy controls. Among these, 65 vOTUs were enriched in PC patients, and 154 were reduced. Host prediction revealed that PC-enriched vOTUs preferentially infected bacterial members of Veillonellaceae, Enterobacteriaceae, Fusobacteriaceae, and Streptococcaceae, while PC-reduced vOTUs were more likely to infect Ruminococcaceae, Lachnospiraceae, Clostridiaceae, Oscillospiraceae, and Peptostreptococcaceae. Furthermore, we constructed random forest models based on the PC-associated vOTUs, achieving an optimal average area under the curve (AUC) of up to 0.879 for distinguishing patients from controls. Through additional 10 public cohorts, we demonstrated the reproducibility and high specificity of these viral signatures. Our study suggests that the gut virome may play a role in PC development and could serve as a promising target for PC diagnosis and therapeutic intervention. Future studies should further explore the underlying mechanisms of gut virus-bacteria interactions and validate the diagnostic models in larger and more diverse populations.

Changes of aqueous humor cytokine profiles of patients with high intraocular pressure after PPV for retinal detachment.

High intraocular pressure (IOP) is one of the early complications after pars plana vitrectomy (PPV), which may cause glaucoma and poor visual prognosis secondary to surgery. Proliferative vitreoretinopathy (PVR) is one of the complications of retinal detachment (RD) and is the main reason for the poor prognosis, which is related to different kinds of cytokines. It's essential for the basic mechanism to analyze the relative aqueous humor cytokine profiles with IOP after PPV for RD. In this study, we have collected the aqueous humor of 16 patients and qualified 27 cytokines using Luminex and compared biomarkers with the high IOP group and the normal group. As a result, the concentrations of VEGF, IL-6, FGF2, and G-CSF upregulated significantly (P < 0.05), while VEGFR2 downregulated significantly (P < 0.05) in the high IOP group. IL-6 was positively correlated with high IOP (r = 0.561, P = 0.041). Meanwhile, the concentrations of IL-6 (r = 0.543, P = 0.03), IL-5 (r = 0.576, P = 0.019), IL-15 (r = 0.614, P = 0.011), IL-4 (r = 0.517, P = 0.04), ICAM-1 (r = 0.611, P = 0.012), and G-CSF (r = 0.636, P = 0.008) were significantly associated with preoperative PVR classification, and the aqueous humor levels of IL-4 (r = 0.567, P = 0.022), HGF (r = 0.701, P = 0.005), and MCP-1 (r = 0.565, P = 0.035) are significant relative to laser points. Hence, cytokines might potentially be the therapeutic target of high IOP after PPV.

Artificial intelligence approaches for phenotyping heart failure in U.S. Veterans Health Administration electronic health record.

AIMS: Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD-code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients. METHODS AND RESULTS: The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP-HF) and non-HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF-related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP-HF as cases (PPV, 0.86; sensitivity, 0.86). From the 'HF ICD-code universe', we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54). CONCLUSIONS: These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.