Epigallocatechin-3-gallate-induced tolerance to cadmium stress involves increased flavonoid synthesis and nutrient homeostasis in tomato roots.

Cadmium (Cd) is a toxic heavy metal, increasingly accumulating in the environment and its presence in various environmental compartments represents a significant risk to human health via the food chain. Epigallocatechin-3-Gallate (EGCG) is a prominent secondary metabolite, which can safeguard plants from biotic and abiotic stress. However, the role of EGCG in flavonoid synthesis, nutrient acquisition and reactive oxygen species (ROS) metabolism under Cd stress remains unclear. Here, we examined the effects of EGCG and Cd treatment on leaf photochemical efficiency, cell ultrastructure, essential element acquisition, antioxidant system, and secondary metabolism in tomato (Solanum lycopersicum L.). The results showed that O2•-, H2O2, and malondialdehyde levels increased after Cd treatment, but Fv/Fm decreased significantly, suggesting that Cd induced oxidative stress and photoinhibition. However, EGCG mitigated the adverse effects of Cd-induced phytotoxicity in both the roots and leaves. A decrease in ROS accumulation under EGCG + Cd treatment was mainly attributed to the significant enhancement in antioxidant enzyme activity, flavonoid content, and PHENYLALANINE AMMONIA-LYASE expression in roots. Moreover, EGCG reduced Cd content but increased some essential nutrient contents in tomato plants. Transmission electron microscopy-based observations revealed that EGCG treatment safeguards leaf and root cell ultrastructure under Cd stress. This implies that tomato plants subjected to Cd stress experienced advantageous effects upon receiving EGCG treatment. The present work elucidated critical mechanisms by which EGCG induces tolerance to Cd, thereby providing a basis for future investigations into environmentally sustainable agricultural practices in areas contaminated with heavy metals, for utilizing naturally occurring substances found in plants.

Perioperative position management of 46 cases with simultaneous bilateral auricle reconstruction: A summary of experience.

OBJECTIVES: The primary problem in simultaneous bilateral auricle reconstruction is the fragility of the reconstructed ear structure. Postoperative pressure is strictly prohibited to ensure the operation's effectiveness. The study aimed to summarize the experience of perioperative postural management in simultaneous bilateral auricular reconstruction. METHOD: This study summarizes the experience of perioperative postural management, providing preoperative sleeping posture adaptability training, neck movement training, standardization of the head position angles and the head suspension time in surgery, using protective headrests, paying attention to the transfer and handover procedures, and using specially designed pillows. RESULTS: The comprehensive nursing approach in simultaneous bilateral auricular reconstruction significantly reduced complications, improved patient comfort, and optimized postoperative adaptation. Preoperative posture training, standardized intraoperative head positions, and vigilant postoperative care played pivotal roles, demonstrating positive outcomes in 46 cases. DISCUSSION: Perioperative position management can reduce the risk of complications and pressure injuries, improving patients' postoperative comfort, emotional state, tolerance, and adaptability. CONCLUSION: All ears were viable and in good shape after long-term follow-up. The experiences discussed in this study can be broadly applied to technically mature ear reconstruction teams.

Alignment Relation is What You Need for Diagram Parsing.

As a knowledge carrier, the diagram is widely distributed in many aspects of human life, such as textbooks, architectural drawings, and documents. Different from natural images, representations of visual elements in the diagram are sparser, and similar visual representations can reflect dissimilar semantics. Thus, current methods fail to capture the visual elements with precise semantics. To address this issue, regarding the aligned visual and textual elements as pairs is the way to assign the precise semantics of textual elements to visual elements. We build the first diagram dataset named align diagram element (ADE), which includes annotations for alignment relations between visual and textual elements. And we propose a visual-textual alignment model (VTAM) including graph construction and optimal aligning phases. In the graph construction phase, the relational graphs are constructed between different elements with four relational operators. The relational operators are designed to measure the relations between different elements, according to distance, connection line, inclusion, and feature similarity. In the optimal aligning phase, the representation at each visual-textual pair is improved as a weighted sum of the representations on all relational graphs. Experimental results show that our VTAM achieves a significant improvement of 10.9% on mean test folds of the ADE dataset than the current best competitor. In order to explore the role of alignment relations in diagram parsing, we introduce VTAM to diagram-related tasks, such as diagram question answering (DQA). And we achieve 2.8% to 5.9% and 4.6% to 5.1% improvements on AI2D and Foodwebs after adding VTAM. Our dataset and code are released at: https://github.com/ADE-dataset/ADE-dataset.

The profile of HIV-1 drug resistance in Shanghai, China: a retrospective study from 2017 to 2021.

BACKGROUND: HIV-1 drug resistance is a huge challenge in the era of ART. OBJECTIVES: To investigate the prevalence and characteristics of acquired HIV-1 drug resistance (ADR) in Shanghai, China. METHODS: An epidemiological study was performed among people living with human immunodeficiency virus (PLWH) receiving ART in Shanghai from January 2017 to December 2021. A total of 8669 PLWH were tested for drug resistance by genotypic resistance testing. Drug resistance mutations (DRMs) were identified using the Stanford University HIV Drug Resistance Database program. RESULTS: Ten HIV-1 subtypes/circulating recombinant forms (CRFs) were identified, mainly including CRF01_AE (46.8%), CRF07_BC (35.7%), B (6.4%), CRF55_01B (2.8%) and CRF08_BC (2.4%). The prevalence of ADR was 48% (389/811). Three NRTI-associated mutations (M184V/I/L, S68G/N/R and K65R/N) and four NNRTI-associated mutations (V179D/E/T/L, K103N/R/S/T, V106M/I/A and G190A/S/T/C/D/E/Q) were the most common DRMs. These DRMs caused high-level resistance to lamivudine, emtricitabine, efavirenz and nevirapine. The DRM profiles appeared to be significantly different among different subtypes. CONCLUSIONS: We revealed HIV-1 subtype characteristics and the DRM profile in Shanghai, which provide crucial guidance for clinical treatment and management of PLWH.

Symptom effects and central mechanism of acupuncture in patients with functional gastrointestinal disorders: a systematic review based on fMRI studies.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are closely related to disorders of brain-gut interaction. FGIDs are the dominant disease of acupuncture treatment, which can improve the symptoms and emotional state. AIM: To evaluate the results and quality of the available clinical evidence and to summarize the central mechanism and effect of acupuncture on FGIDs. METHODS: PubMed, EMBASE, Web of science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched by computer to collect the randomized controlled trials (RCTs), which contained central mechanisms via fMRI research of acupuncture in the treatment of FGIDs patients. The search time limit was from the establishment of the database to June 22, 2022. Two researchers independently screened the literature, extracted data, and evaluated the quality. RESULTS: Ten RCTs involving fMRI data were included in this study, including 4 Functional dyspepsia (FD) studies, 3 irritable bowel syndrome (IBS) studies, and 3 functional constipation (FC) studies. The score of improvements in both gastrointestinal symptoms and psychological symptoms showed that acupuncture could significantly improve the clinical symptoms of FGIDs patients, including abdominal pain, abdominal distension, frequency of defecation, and stool characteristics, and could relieve anxiety and depression symptoms of patients. Acupuncture could regulate brain functional connections and functional activity in FGIDs patients, mainly including insula, anterior cingulate cortex, prefrontal cortex, thalamus, hippocampus, amygdala and other brain regions. CONCLUSION: Acupuncture can improve gastrointestinal symptoms and psychological status in FGIDs patients, and regulate functional connectivity and activity of brain regions such as insula, ACC, PFC, thalamus, HIPP, amygdala, etc. These changes in brain activity may related to visceral sensation, pain regulation, emotion, but further studies of high quality are still necessary.

Effects of Differential Shading on Summer Tea Quality and Tea Garden Microenvironment.

Shading is an effective agronomic technique to protect tea plants from intense sunlight. However, there are currently very few studies on more effective shading methods to improve the quality of summer tea. In this study, 'Longjing43' plants were grown under four different shading treatments for 14 days, with no shading as the control. Among the four shading treatments, double-layer-net shadings had the most positive impact on the tea quality, resulting in higher levels of amino acids but lower levels of tea polyphenols. Additionally, double-layer-net shadings provided more suitable microenvironments for tea plants. The tea leaves in T4 (double nets 50 cm above the plant canopy) contained 16.13 mg∙g-1 of umami and sweet amino acids, which was significantly higher than in other treatments. T4 had the lowest air temperature and the most suitable and stable soil water content. Interestingly, the ratio of red light to far-red light in T4 was only 1.65, much lower than other treatments, which warrants further study. In conclusion, the microenvironment induced by shading can greatly affect the tea quality, and double-layer-net shading is better for improving the quality of summer tea.

A new double-antigen sandwich test based on the light-initiated chemiluminescent assay for detecting anti-hepatitis C virus antibodies with high sensitivity and specificity.

Objectives: The aim of this study was to evaluate the performance of a new double-antigen sandwich test that is based on the light-initiated chemiluminescent assay (LiCA®) for detecting anti-hepatitis C virus antibodies (anti-HCV) in comparison to Architect®. Methods: Analytical characteristics and diagnostic performance were tested using seroconversion panels and large pools of clinical samples. Positive results were validated by the strip immunoblot assay (RIBA) and HCV RNA. Results: Repeatability and within-lab imprecision of LiCA® anti-HCV were 1.31%-3.27%. The C5-C95 interval was -5.44%-5.03% away from C50. LiCA® detected seroconversion in an average of 28.9 days and showed a mean of 3.7 (p = 0.0056) days earlier than Architect®. In a pool of 239 samples with known HCV genotypes 1 to 6, both assays correctly detected all subjects. In 16,305 clinical patient sera, LiCA® detected 4 false-negative (0.25‰) and 14 false-positive (0.86‰) anti-HCV cases, while Architect® recorded 6 false-negative (0.37‰) and 138 false-positive (8.46‰) subjects, respectively. Compared to Architect®, LiCA® presented a significantly better performance in specificity (99.91% vs. 99.14%, n = 16,018, p < 0.0001), positive predictive value (95.29% vs. 67.06%, n = 419, p < 0.0001), and overall accuracy (99.89% vs. 99.12%, n = 16,305, p < 0.0001), while no significant difference in sensitivity (98.61% vs. 97.91%, n = 287, p = 0.5217) and negative predictive value (99.98% vs. 99.96%, n = 15,886, p = 0.3021) was seen. An S/Co value of 3.28 was predicted to be the threshold with a positivity ≥95% for the LiCA® anti-HCV assay. Conclusion: LiCA® anti-HCV is a precise and fully automatic chemiluminescent assay with superior sensitivity and specificity. The assay can be used as a valuable tool to supplement the diagnosis of HCV infection.

Prognostic Factors of Severe Pneumonia in Adult Patients: A Systematic Review.

Objectives: This systematic review aimed to identify independent prognostic factors of severe pneumonia. Methods: A systematic search was undertaken in Pubmed, Embase, and Web of Science from inception to March 2023 to find cohort studies investigating the association between prognostic factors and adverse outcomes of severe pneumonia in adult patients. The study selection process involved screening the title and abstract of articles to identify relevant studies on severe pneumonia in adult patients. Inclusion criteria included studies with a prospective or retrospective longitudinal design, investigating prognostic factors, and performing multivariate analysis. Exclusion criteria included non-English or non-Chinese studies, studies focusing on severe pneumonia in children, studies conducting only univariate analysis, and conference abstracts, reviews, and case reports. The risk of bias was assessed by the Quality In Prognosis Studies (QUIPS) tool. Results: A total of 27 published studies, including both prospective and retrospective cohort studies, were included. These studies reported on 53 different prognostic factors and covered four unique outcomes. The quality assessment indicated that 59.3% of the studies had a low risk of bias. Age, functional dependence, heart rate, and oxygen saturation/respiratory rate index were found to be associated with mortality. Additionally, various laboratory indexes, such as serum cholinesterase, albumin, and blood urea nitrogen to creatinine ratio, demonstrated either protective or risk factors for prognosis. Injury and comorbidities, including acute renal failure, chronic lung disease, and Glasgow Coma Scale, were identified as risk factors for mortality. Scoring tools like Acute Physiological and Chronic Health Evaluation (APACHE) II score, CURB-65 score, and Pneumonia Severity Index (PSI) score showed associations with mortality. Lastly, certain treatment protocols, such as vasoactive agent use, vasopressor use, and mechanical ventilation, were found to increase the risk of mortality, while invasive mechanical ventilation and the use of remdesivir and steroids had a positive impact on prognosis. These findings provide valuable insights for clinicians in predicting and managing severe pneumonia outcomes. Conclusion: This most comprehensive review identified 53 unique prognostic factors of severe pneumonia, which provided a reference for subsequent researchers to construct models to predict clinical outcomes in patients with severe pneumonia for clinical use. By identifying prognostic factors through multivariate analysis, healthcare providers can better assess the severity and prognosis of individual patients. This knowledge can aid in treatment planning, resource allocation, and determining the appropriate level of care for patients with severe pneumonia. Additionally, understanding the prognostic factors can help identify high-risk patients who may require more intensive monitoring or interventions. Overall, this study provides valuable insights that can inform clinical practice and improve patient outcomes in the management of severe pneumonia.

DisAVR: Disentangled Adaptive Visual Reasoning Network for Diagram Question Answering.

Diagram Question Answering (DQA) aims to correctly answer questions about given diagrams, which demands an interplay of good diagram understanding and effective reasoning. However, the same appearance of objects in diagrams can express different semantics. This kind of visual semantic ambiguity problem makes it challenging to represent diagrams sufficiently for better understanding. Moreover, since there are questions about diagrams from different perspectives, it is also crucial to perform flexible and adaptive reasoning on content-rich diagrams. In this paper, we propose a Disentangled Adaptive Visual Reasoning Network for DQA, named DisAVR, to jointly optimize the dual-process of representation and reasoning. DisAVR mainly comprises three modules: improved region feature learning, question parsing, and disentangled adaptive reasoning. Specifically, the improved region feature learning module is designed to first learn robust diagram representation by integrating detail-aware patch features and semantically-explicit text features with region features. Subsequently, the question parsing module decomposes the question into three types of question guidance including region, spatial relation and semantic relation guidance to dynamically guide subsequent reasoning. Next, the disentangled adaptive reasoning module decomposes the whole reasoning process by employing three visual reasoning cells to construct a soft fully-connected multi-layer stacked routing space. These three cells in each layer reason over object regions, semantic and spatial relations in the diagram under the corresponding question guidance. Moreover, an adaptive routing mechanism is designed to flexibly explore more optimal reasoning paths for specific diagram-question pairs. Extensive experiments on three DQA datasets demonstrate the superiority of our DisAVR.

Impact of Endolymphatic Hydrops and Semicircular Canal Dysfunction on the Incomplete Recovery of Acute Low-Frequency Sensorineural Hearing Loss.

OBJECTIVE: The reasons for short-term, incomplete recovery of some acute low-frequency sensorineural hearing loss (ALFHL) are unclear. We investigated the impact of endolymphatic hydrops and semicircular canal dysfunction on the incomplete recovery of ALFHL. METHODS: The impact of electrocochleography (EcochG), caloric test, video head impulse test (vHIT), cervical vestibular-evoked myogenic potential (cVEMP), and ocular vestibular-evoked myogenic potential (oVEMP) results on the incomplete recovery of 86 patients with ALFHL was analyzed. The correlation between a high abnormal rate of vestibular-evoked myogenic potential (VEMP) and aural fullness, dizziness, and level of hearing loss was also examined. RESULTS: Abnormal oVEMP with an odds ratio (OR) of 6.071 (P = .002) and EcochG with an OR of 5.919 (P = .005) were independent risk factors for incomplete recovery in ALFHL, but abnormal cVEMP, caloric test, and vHIT were not independent risk factors for ALFHL. There was no correlation between a high abnormal rate of VEMP and aural fullness, dizziness, or level of hearing loss in ALFHL. CONCLUSION: Abnormal oVEMP and EcochG values rather than caloric test and vHIT were risk factors for incomplete recovery of ALFHL, which may be related to the difficulty of successfully treating utricular and cochlear hydrops. High abnormal rate of VEMP was not correlated with hearing loss level, aural fullness, or dizziness in ALFHL. Abnormal oVEMP and EcochG values can indicate poor short-term prognosis of ALFHL.

Identification of renal cyst cells of type I Nephronophthisis by single-nucleus RNA sequencing.

Background: Nephronophthisis (NPH) is the most common genetic cause of end-stage renal disease (ESRD) in childhood, and NPHP1 is the major pathogenic gene. Cyst formation at the corticomedullary junction is a pathological feature of NPH, but the mechanism underlying cystogenesis is not well understood. The isolation and identification of cystic cell subpopulation could help to identify their origins and provide vital clues to the mechanisms underlying cystogenesis in NPH. Methods: Single-nucleus RNA sequencing (snRNA-seq) was performed to produce an atlas of NPHP1 renal cells. Kidney samples were collected from WT (Nphp1 +/+) mice and NPHP1 (Nphp1 del2-20/del2-20) model mice. Results: A comprehensive atlas of the renal cellular landscape in NPHP1 was generated, consisting of 14 basic renal cell types as well as a subpopulation of DCT cells that was overrepresented in NPHP1 kidneys compared to WT kidneys. GO analysis revealed significant downregulation of genes associated with tubular development and kidney morphogenesis in this subpopulation. Furthermore, the reconstruction of differentiation trajectories of individual cells within this subpopulation confirmed that a specific group of cells in NPHP1 mice become arrested at an early stage of differentiation and proliferate to form cysts. We demonstrate that Niban1 is a specific molecular marker of cystic cells in both mice and human NPHP1. Conclusion: In summary, we report a novel subpopulation of DCT cells, marked by Niban1, that are classified as cystic cells in the NPHP1 mice kidney. These results offer fresh insights into the cellular and molecular basis of cystogenesis in NPH.

Self-constrained DNAzyme for aptamer-based and sensitive label-free fluorescent assay of sarafloxacin via signal amplification cascades.

The convenient and sensitive assay of antibiotic residuals is important for monitoring food safety and human health. Here, with a new self-constrained metal ion-dependent DNAzyme and hybridization chain reaction (HCR) signal amplifications, a simple label-free and highly sensitive aptamer-based fluorescent sensing assay for sarafloxacin is established. The target sarafloxacin molecules bind the aptamers in the duplex DNA probes to release the complementary strands, which cyclically activate the catalytic activity of the self-constrained DNAzymes to cut the substrate sequences to liberate many ssDNA strands. Subsequent HCR of two hairpins is initiated by these ssDNA strands for yielding long dsDNAs with lots of G-quadruplexes, which intercalate thioflavin T dye to generate drastically magnified fluorescence for non-label and sensitive sarafloxacin detection at the detection limit of 29 pM. Also, a highly selective assay of low levels of sarafloxacin in diluted milk samples has been demonstrated, showing the great potential of our approach for the development of versatile sensitive and convenient aptasensors for monitoring different antibiotics.

Genome-wide identification of genes encoding SWI/SNF components in soybean and the functional characterization of GmLFR1 in drought-stressed plants.

ATP-dependent SWI/SNF chromatin remodeling complexes (CRCs) are evolutionarily conserved multi-component machines that regulate transcription, replication, and genome stability in eukaryotes. SWI/SNF components play pivotal roles in development and various stress responses in plants. However, the compositions and biological functions of SWI/SNF complex subunits remain poorly understood in soybean. In this study, we used bioinformatics to identify 39 genes encoding SWI/SNF subunit distributed on the 19 chromosomes of soybean. The promoter regions of the genes were enriched with several cis-regulatory elements that are responsive to various hormones and stresses. Digital expression profiling and qRT-PCR revealed that most of the SWI/SNF subunit genes were expressed in multiple tissues of soybean and were sensitive to drought stress. Phenotypical, physiological, and molecular genetic analyses revealed that GmLFR1 (Leaf and Flower-Related1) plays a negative role in drought tolerance in soybean and Arabidopsis thaliana. Together, our findings characterize putative components of soybean SWI/SNF complex and indicate possible roles for GmLFR1 in plants under drought stress. This study offers a foundation for comprehensive analyses of soybean SWI/SNF subunit and provides mechanistic insight into the epigenetic regulation of drought tolerance in soybean.

Sequential Administration of SARS-CoV-2 Strains-Based Vaccines Effectively Induces Potent Immune Responses against Previously Unexposed Omicron Strain.

In the past few years, the continuous pandemic of COVID-19 caused by SARS-CoV-2 has placed a huge burden on public health. In order to effectively deal with the emergence of new SARS-CoV-2 variants, it becomes meaningful to further enhance the immune responses of individuals who have completed the first-generation vaccination. To understand whether sequential administration using different variant sequence-based inactivated vaccines could induce better immunity against the forthcoming variants, we tried five inactivated vaccine combinations in a mouse model and compared their immune responses. Our results showed that the sequential strategies have a significant advantage over homologous immunization by inducing robust antigen-specific T cell immune responses in the early stages of immunization. Furthermore, the three-dose vaccination strategies in our research elicited better neutralizing antibody responses against the BA.2 Omicron strain. These data provide scientific clues for finding the optimal strategy within the existing vaccine platform in generating cross-immunity against multiple variants including previously unexposed strains.

Aldosterone inhibits Dot1l expression in guinea pig cochlea.

BACKGROUND: Aldosterone relieves transcriptional repression of epithelial sodium channel (ENaC) by inhibiting Dot1a and Af9 expression and their interaction with ENaC promoter in various tissues. Expressions of ENaC and Af9 in inner ear have been identified. However, it is not known how Dot1l is regulated by aldosterone in inner ear. METHODS: Twenty-eight adult guinea pigs were randomly divided into the control group and treatment group. Aldosterone 1 mg/kg/d was injected intraperitoneally in the treatment group and saline in the control group for 7 days. Animals were killed 1 month later following auditory brainstem response examination. Histomorphology of cochlea was detected with hematoxylin-eosin staining, and Dot1l expression was examined with immunohistochemistry and Western blot. RESULTS: There was no significant difference in ABR thresholds before and after injection of aldosterone or saline in either group. Endolymphatic hydrops was found in 75% of animals in the treatment group. Dot1l was found in both groups in the stria vascularis, Reissner's membrane, spiral limbus, organ of Corti and spiral ligament. Dot1l expression in the treatment group was decreased by aldosterone. CONCLUSIONS: Dot1l in guinea pig cochlea is inhibited by aldosterone with induction of endolymphatic hydrops. Dot1l may be closely related to endolymph regulation by aldosterone and to pathogenesis of Meniere's disease.

Induced circular dichroism of achiral dielectric elliptical hole arrays with a monolayer borophene film.

Induced circular dichroism (ICD) is widely used in miniature polarizers, molecular detection, and negative refractive index media. However, enhancing and the dynamic regulation of ICD signals of achiral nanostructures in the visible and near-infrared range remain the current challenges. Here, monolayer borophene (MB) with anisotropic conductance was incorporated into achiral nanostructures, which consisted of achiral dielectric elliptical hole arrays (DENAs) placed on a silver substrate. Two narrowband ICD signals for DENAs/MB were achieved in the near-infrared range under different circularly polarized lights. The distributions of the magnetic field of DENAs/MB could explain the two narrowband ICD signals originating from the coupling of surface plasmon polariton resonances along the x- and y directions. Not only could the ICD signals be tuned by the structural parameters of DENAs/MB, but they could also be actively tuned by the incident angles of the excitation light and the carrier concentration of MB. In addition, the sensitivity and the figure of merit of DENAs/MB could reach 302/RIU and 61.0. These results provide a concise method for the design of dynamically adjustable chiral devices based on borophene and promote its application in molecular recognition and chiral catalysis.

A review on development of placental transfusion in term and preterm infants.

In recent years, it has been verified that placental transfusion can replenish blood volume of neonates, improve organ perfusion in the early postnatal stage, and facilitate the transition from fetal circulation to adult circulation. Meanwhile, placental transfusion can reduce the need for blood transfusion and the onset of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, and other complications. Furthermore, it can improve the iron store and the long-term prognosis of central nervous system, and reduce infant mortality. Different methods have been used, including delayed cord clamping, intact umbilical cord milking, and cut umbilical cord milking. The World Health Organization (WHO) and other academic organizations recommend the routine use of delayed cord clamping at birth for the most vigorous term and preterm neonates. However, details of placental transfusion should be clarified, and the short/long-term impacts of this technology on some infants with special conditions still require further study.

PICO entity extraction for preclinical animal literature.

BACKGROUND: Natural language processing could assist multiple tasks in systematic reviews to reduce workflow, including the extraction of PICO elements such as study populations, interventions, comparators and outcomes. The PICO framework provides a basis for the retrieval and selection for inclusion of evidence relevant to a specific systematic review question, and automatic approaches to PICO extraction have been developed particularly for reviews of clinical trial findings. Considering the difference between preclinical animal studies and clinical trials, developing separate approaches is necessary. Facilitating preclinical systematic reviews will inform the translation from preclinical to clinical research. METHODS: We randomly selected 400 abstracts from the PubMed Central Open Access database which described in vivo animal research and manually annotated these with PICO phrases for Species, Strain, methods of Induction of disease model, Intervention, Comparator and Outcome. We developed a two-stage workflow for preclinical PICO extraction. Firstly we fine-tuned BERT with different pre-trained modules for PICO sentence classification. Then, after removing the text irrelevant to PICO features, we explored LSTM-, CRF- and BERT-based models for PICO entity recognition. We also explored a self-training approach because of the small training corpus. RESULTS: For PICO sentence classification, BERT models using all pre-trained modules achieved an F1 score of over 80%, and models pre-trained on PubMed abstracts achieved the highest F1 of 85%. For PICO entity recognition, fine-tuning BERT pre-trained on PubMed abstracts achieved an overall F1 of 71% and satisfactory F1 for Species (98%), Strain (70%), Intervention (70%) and Outcome (67%). The score of Induction and Comparator is less satisfactory, but F1 of Comparator can be improved to 50% by applying self-training. CONCLUSIONS: Our study indicates that of the approaches tested, BERT pre-trained on PubMed abstracts is the best for both PICO sentence classification and PICO entity recognition in the preclinical abstracts. Self-training yields better performance for identifying comparators and strains.

The Diagnostic and Prognostic Values of HOXA Gene Family in Kidney Clear Cell Renal Cell Carcinoma.

Kidney renal clear cell carcinoma (KIRC) is one of the most common cancers with high mortality worldwide. As members of the homeobox (HOX) family, homeobox-A (HOXA) genes have been reported to play an increasingly important role in tumorigenesis and the progression of multiple cancers. However, limited studies have investigated the potential diagnostic and prognostic roles of HOXA genes in KIRC. In this research, we explored the expression pattern of the HOXA gene family in KIRC progression by differential analysis of expression profiles from The Cancer Genome Atlas (TCGA). By using univariate Cox analysis and lasso regression analysis, we comprehensively evaluated the prognostic value of HOXA genes and eventually identified a prognostic risk model consisting of five HOXA genes (HOXA2, HOXA3, HOXA7, HOXA11, and HOXA13). The risk model was further validated as a novel independent prognostic factor for KIRC patients based on the calculated risk score by Kaplan-Meier analysis, univariate and multivariate Cox regression analyses, and time-dependent receiver operating characteristic (ROC) curve analysis. Moreover, to explore the potential mechanism of tumorigenesis and clinical application of KIRC, we also developed the HOXA-based competing endogenous RNA (ceRNA) regulatory network and machine learning classification model. Valproic acid and tretinoin were predicted to be the most promising small molecules to adjuvant treatment of KIRC by mining the CMAP and DGIdb drug database. Subsequently, pathway and functional enrichment analyses provided us with new ways to search for a possible mechanism of action of drugs. Taken together, our study demonstrated the nonnegligible role of HOXA genes in KIRC and constructed an effective prognostic and diagnostic model, which offers novel insights into KIRC prognosis.

Two-Dimensional Self-Assembly of Au@Ag Core-Shell Nanocubes with Different Permutations for Ultrasensitive SERS Measurements.

Different self-assembly methods not only directly change the arrangement of noble metal particles on the substrate but also indirectly affect the local electromagnetic field distribution and intensity of the substrate under specific optical excitation conditions, which leads to distinguished different enhancement effects of the structure on molecular Raman signals. In this paper, first, the gold species growth method was used to prepare the silver-coated gold nanocubes (Au@Ag NCs) with regular morphology and uniform size, and then the two-phase and three-phase liquid-liquid self-assembly and evaporation-induced self-assembly methods were used to obtain the substrate structure with different NC arrangement patterns. The optimal arrangement of NCs was found by transverse comparison of Raman signal detection of probe molecules with the same concentration. Subsequently, surface-enhanced Raman scattering (SERS) measurements of Rhodamine (Rh6G) and aspartame (APM) were carried out. Furthermore, the finite element method (FEM) was employed to calculate the local electromagnetic fields of the substrates with different Au@Ag NC arrangements, and the calculated results were in agreement with the experimental results. The experimental results show that the SERS-active substrate was largely associated with the different arrangements of Au@Ag NCs, and the island membrane Au@Ag NCs array substrate obtained by evaporation-induced self-assembly can generate a strong local electromagnetic field due to the edge and corner bonding gap between the tightly arranged NCs; this endows the substrate with benign sensitivity and reproducibility and has great potential in molecular detection, biosensing, and food safety monitoring.