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This study provides a comprehensive analysis of global, continental, and national trends in the prevalence and mortality of prostate cancer (PC), breast cancer (BC), and thyroid cancer (TC). Utilizing 2021 Global Burden of Diseases (GBD2021) data, prevalence and death rates for 2021 were examined, with temporal trends from 1990 to 2021 analyzed via Joinpoint regression. Annual percentage change (APC) and average APC (AAPC) were calculated with 95% confidence intervals (CI). Distributive inequalities were quantified using the slope index of inequality and concentration index. In 2021, PC, BC, and TC showed higher global age-standardized prevalence rates (ASPR) in Europe and America compared to Africa and Asia, while higher age-standardized death rates (ASDR) for PC and BC were noted in Africa. Over the study period, significant global increases in ASPR were observed for PC (AAPC = 0.78, 95% CI: 0.67 to 0.89), BC (AAPC = 0.31, 95% CI: 0.24 to 0.37), and TC (AAPC = 1.42, 95% CI: 1.31 to 1.52). Conversely, ASDR significantly decreased for PC (AAPC = -0.83, 95% CI: -0.92 to -0.74), BC (AAPC = -0.48, 95% CI: -0.56 to -0.39), and TC (AAPC = -0.23, 95% CI: -0.29 to -0.17). Variations were observed across continents and time periods, affecting 204 countries and territories. higher social development index (SDI) levels were associated with a more pronounced burden of these cancers. The findings highlight significant global heterogeneity in prevalence, death rates, and temporal trends of endocrine cancers, with important implications for epidemiology and public health policies.
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OBJECTIVE: This study was designed to evaluate the five-year overall survival (OS) rate and postoperative survival time of patients diagnosed with oral squamous cell carcinoma (OSCC), as well as examine the clinical and pathological factors influencing survival outcomes in OSCC patients. METHODS: Data were collected from OSCC patients who underwent their first radical surgical intervention in the Department of Maxillofacial Surgery at the First Affiliated Hospital of Chongqing Medical University between April 2014 and December 2016. Follow-up was conducted until March 2022. RESULTS: The study included a total of 162 patients. The observed 5-year OS rate was 59.3%. Approximately 45.7% of OSCC patients experienced postoperative recurrence or metastasis, with a 5-year overall disease-free survival rate of 49.4%. There was no significant difference in the impact of sex, age, smoking, alcohol consumption, primary tumour location, depth of invasion or primary tumour size on the 5-year survival rate (p > 0.05). Univariate analysis revealed that clinical stage (Hazard Ratio = 2.239, p = 0.004), perineural invasion (PNI) (Hazard Ratio = 1.712, p = 0.03), lymph node metastasis (pN) (Hazard Ratio = 2.119, p = 0.002), pathological differentiation (Hazard Ratio = 2.715, p < 0.001), and recurrence or metastasis (Hazard Ratio = 10.02, p < 0.001) were significant factors influencing survival. Multivariate analysis further indicated that pathological differentiation (Hazard Ratio = 2.291, p = 0.001), PNI (Hazard Ratio = 1.765, p = 0.031) and recurrence or metastasis (Hazard Ratio = 9.256, p < 0.001) were independent risk factors of survival. Intriguingly, 11 OSCC patients were diagnosed with oesophageal squamous cell carcinoma (ESCC) within 1-4 years following surgery. CONCLUSION: The survival prognosis of OSCC patients is significantly associated with clinical stage, PNI, lymph node metastasis, pathological differentiation, and recurrence or metastasis. Pathological differentiation, PNI and recurrence or metastasis are independent risk factors affecting survival. Routine clinical screening for ESCC may be recommended for OSCC patients with a history of alcohol consumption and tobacco use.
Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Humans , Male , Female , Mouth Neoplasms/surgery , Mouth Neoplasms/pathology , Mouth Neoplasms/mortality , Middle Aged , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Aged , Survival Rate , Survival Analysis , Adult , Neoplasm Recurrence, Local , Lymphatic Metastasis , Risk Factors , Neoplasm Staging , Aged, 80 and overABSTRACT
BACKGROUND: This prospective study aimed to evaluate the outcomes of the use of dermal templates for lengthy volar soft tissue defects (1.5-4â¯cm) in the fingers. METHODS: The volar soft tissue defects of 15 patients (19 fingers) were treated with Lando dermal template coverage between June 2022 and November 2022. We evaluated sensory recovery, scar formation, and overall appearance of the repair site at an average of 13â¯months (range, 12-17â¯months) of follow-up. RESULTS: The defect healed in all cases. We found an average static 2-point discrimination of 7â¯mm (range 4 to 14â¯mm). Scar formation was evident in all cases. The repair did not restore the bulkiness of the volar finger, especially in the finger with the bony exposure. Nail deformities and joint contracture were observed in some cases. CONCLUSION: Dermal template repair does not restore normal sensation and inevitably leads to scar formation when the defect is longer (>1.5â¯cm). Bulkiness of the volar finger is not restored in most patients, especially when there was bone or tendon exposure in the initial wound site.
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Recent advancements in biomedical research have underscored the importance of noninvasive cellular manipulation techniques. Sonogenetics, a method that uses genetic engineering to produce ultrasound-sensitive proteins in target cells, is gaining prominence along with optogenetics, electrogenetics, and magnetogenetics. Upon stimulation with ultrasound, these proteins trigger a cascade of cellular activities and functions. Unlike traditional ultrasound modalities, sonogenetics offers enhanced spatial selectivity, improving precision and safety in disease treatment. This technology broadens the scope of non-surgical interventions across a wide range of clinical research and therapeutic applications, including neuromodulation, oncologic treatments, stem cell therapy, and beyond. Although current literature predominantly emphasizes ultrasonic neuromodulation, this review offers a comprehensive exploration of sonogenetics. We discuss ultrasound properties, the specific ultrasound-sensitive proteins employed in sonogenetics, and the technique's potential in managing conditions such as neurological disorders, cancer, and ophthalmic diseases, and in stem cell therapies. Our objective is to stimulate fresh perspectives for further research in this promising field.
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Introduction: Baló's concentric sclerosis (BCS) is a rare type of central nervous system demyelinating disorder. Most patients with BCS are treated with corticosteroids, and spontaneous remission has seldom been described. Case presentation: A 46-year-old man presented with a subacute-onset headache and memory loss. Brain magnetic resonance imaging (MRI) revealed multiple onion-shaped ring lesions with mild enhancement in the outermost ring. A brain biopsy revealed significant myelin loss. The diagnosis of BCS was established based on the MRI results and pathological findings. Interestingly, the patient recovered almost completely without immunotherapy, with repeated brain MRI at the 1-year follow-up showing an obvious reduction in the extent of the lesions. Conclusion: Neurologists should improve the recognition of the typical MRI features of BCS to avoid unnecessary biopsies. Although rare, spontaneous remission can be observed in clinical practice.
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Ag nanocomposites (NAs) have been found to induce irreversible harm to pathogenic bacteria, however, NAs tend to aggregate easily when used alone. These nanocomposites also show increased toxicity and their underlying antibacterial mechanism is still unknown. In short, practical applications of NA materials face the following obstacles: elucidating the mechanism of antibacterial action, reducing cytotoxicity to body cells, and enhancing antibacterial activity. This study synthesized a core-shell structured ZnFe2O4 @Cu-ZIF-8 @Ag (FUA) nanocomposite with high antibacterial activity and low cytotoxicity. The nanocomposites achieved a 99.99 % antibacterial rate against Escherichia coli (E. coli) and tetracycline-resistant E. coli (T - E. coli), in under 20 min at 100 µg/mL. The nanocomposites were able to inactivate E. coli due to the gradual release of Cu2+, Zn2+, and Ag+ ions, which synergistically form â¢OH from FUA in an aerobic environment. The presence of â¢OH has significant effects on the antibacterial activity. The released metal ions combine with â¢OH to cause damage to the bacterial cell wall, resulting in the leakage of electrolytes and ions. Moreover, in comparison to NA, the toxicity of FUA is considerably reduced. This study is expected to inspire the development of other silver-based nanocomposite materials for the inactivation of drug-resistant bacteria.
Subject(s)
Anti-Bacterial Agents , Escherichia coli , Nanocomposites , Silver , Escherichia coli/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Nanocomposites/chemistry , Nanocomposites/toxicity , Silver/chemistry , Silver/toxicity , Silver/pharmacology , Copper/chemistry , Copper/toxicity , Copper/pharmacology , Microbial Sensitivity Tests , Zinc/chemistry , Zinc/pharmacology , Animals , Metal Nanoparticles/toxicity , Metal Nanoparticles/chemistryABSTRACT
Covalent and oriented immobilization of antibodies (Abs) can substantially improve the sensitivity and stability of solid-phase immunoassays. By modifying the natural Abs with functional groups that provide unique handles for further conjugation, Abs could be immobilized onto the solid matrices with uniform orientation. Herein, an effective approach for Fc-specific modification of Abs was developed for the oriented and covalent immobilization of Abs. Twelve photoreactive Z-domain variants, incorporated with a photoactivable probe (p-benzoyl-L-phenylalanine, Bpa) at different positions and carrying a C-terminal Cys-tag (i.e. ZBpa-Cys variants), were individually constructed and produced in Escherichia coli and tested for photo-cross-linking to various IgGs. The different ZBpa-Cys variants demonstrated large differences in photo-conjugation efficiency for the tested IgGs. The conjugation efficiencies of 17thZBpa-Cys ranged from 90 % to nearly 100 % for rabbit IgG and mouse IgG2a, IgG2b and IgG3. Other variants, including 5thZBpa-Cys, 18thZBpa-Cys, 32thZBpa-Cys, and 35thZBpa-Cys, also displayed conjugation efficiencies of 61 %-83 % for mouse IgG1, IgG2a and IgG3. Subsequently, the photo-modified Abs, namely IgG-Cys conjugates, were covalently immobilized onto a maleimide group-functionalized solid-phase carrier on the basis of the reaction of sulfhydryl and maleimide. Thus, a generic platform for the controlled and oriented immobilization of Abs was developed, and the efficacy and potential of the proposed approach for sensitive immunoassays was demonstrated by detecting human α-fetoprotein.
Subject(s)
Antibodies, Immobilized , Cysteine , Immunoglobulin Fc Fragments , Immunoglobulin G , Cysteine/chemistry , Animals , Immunoglobulin G/chemistry , Immunoglobulin G/immunology , Immunoglobulin Fc Fragments/chemistry , Antibodies, Immobilized/chemistry , Antibodies, Immobilized/immunology , Mice , Rabbits , Phenylalanine/chemistry , Phenylalanine/analogs & derivatives , Immunoassay/methods , Escherichia coli , Antibodies/chemistry , Antibodies/immunologyABSTRACT
Organophosphate esters (OPEs) are one of the emerging environmental threats, causing the hazard to ecosystem safety and human health. Yet, the toxic effects and metabolic response mechanism after Escherichia coli (E.coli) exposed to TDCIPP and TEHP is inconclusive. Herein, the levels of SOD and CAT were elevated in a concentration-dependent manner, accompanied with the increase of MDA contents, signifying the activation of antioxidant response and occurrence of lipid peroxidation. Oxidative damage mediated by excessive accumulation of ROS decreased membrane potential and inhibited membrane protein synthesis, causing membrane protein dysfunction. Integrative analyses of GC-MS and LC-MS based metabolomics evinced that significant perturbation to the carbohydrate metabolism, nucleotide metabolism, lipids metabolism, amino acid metabolism, organic acids metabolism were induced following exposure to TDCIPP and TEHP in E.coli, resulting in metabolic reprogramming. Additionally, metabolites including PE(16:1(5Z)/15:0), PA(17:0/15:1(9Z)), PC(20:2(11Z,14Z)/12:0), LysoPC(18:3(6Z,9Z,12Z)/0:0) were significantly upregulated, manifesting that cell membrane protective molecule was afforded by these differential metabolites to improve permeability and fluidity. Overall, current findings generate new insights into the molecular toxicity mechanism by which E.coli respond to TDCIPP and TEHP stress and supply valuable information for potential ecological risks of OPEs on aquatic ecosystems.
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To utilize the resource of working memory efficiently, the brain actively suppresses irrelevant information to focus cognitive resources on the task at hand. However, whether task-irrelevant self-related information can be suppressed is still an open question. This study explores the inhibitory effects of various types of identity-associated information (self, friend, stranger) with an irrelevant distracting paradigm, in which participants are required to memorize the color while ignoring the shape during a memory array. In the subsequent test array, participants are asked to judge whether the color of the test item is the same as the memorized one, while the ignored shape features could also change. The results are as follows. (1) Self-associated information survived the inhibitory effect no matter whether the interstimulus interval (ISI) was short or long. (2) Stranger-associated information remained inhibitory effect in a long ISI (3000 ms). The results indicate that self-associated information can bypass the executive system and remain active in working memory processing.
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Mutations in amino acid sequences can provoke changes in protein function. Accurate and unsupervised prediction of mutation effects is critical in biotechnology and biomedicine, but remains a fundamental challenge. To resolve this challenge, here we present Protein Mutational Effect Predictor (ProMEP), a general and multiple sequence alignment-free method that enables zero-shot prediction of mutation effects. A multimodal deep representation learning model embedded in ProMEP was developed to comprehensively learn both sequence and structure contexts from ~160 million proteins. ProMEP achieves state-of-the-art performance in mutational effect prediction and accomplishes a tremendous improvement in speed, enabling efficient and intelligent protein engineering. Specifically, ProMEP accurately forecasts mutational consequences on the gene-editing enzymes TnpB and TadA, and successfully guides the development of high-performance gene-editing tools with their engineered variants. The gene-editing efficiency of a 5-site mutant of TnpB reaches up to 74.04% (vs 24.66% for the wild type); and the base editing tool developed on the basis of a TadA 15-site mutant (in addition to the A106V/D108N double mutation that renders deoxyadenosine deaminase activity to TadA) exhibits an A-to-G conversion frequency of up to 77.27% (vs 69.80% for ABE8e, a previous TadA-based adenine base editor) with significantly reduced bystander and off-target effects compared to ABE8e. ProMEP not only showcases superior performance in predicting mutational effects on proteins but also demonstrates a great capability to guide protein engineering. Therefore, ProMEP enables efficient exploration of the gigantic protein space and facilitates practical design of proteins, thereby advancing studies in biomedicine and synthetic biology.
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The immune system can lead to a variety of renal diseases through direct or indirect mechanisms. In immune-mediated nephropathy, though standardized treatment, there are still a small number of patients with further decline in renal function, which may even progress to renal failure; sodium-glucose cotransporter protein 2 (SLC5A2,SGLT2) inhibitors not only can significantly reduce blood glucose, but also have an additional protective effect on the kidneys and the heart; this review concludes the potential mechanism of the renal protective effect of SGLT2i and the new advances in the recent years in common immune-mediated nephropathies, which can provide new theoretical references to optimize the therapeutic strategy of common immune-mediated nephropathies.
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BACKGROUND: The expression patterns and prognostic value of Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family genes in breast cancer remain to be elucidated. METHODS: The expression levels, prognostic value, and biological function of PLODs were determined using Oncomine, cBioPortal, GEPIA, Timer, UALCAN, PrognoScan, GeneMANIA, Metascape, and breast cancer tissue microarrays. RESULTS: The expressions of PLOD1 and PLOD3 were upregulated in breast cancer tissues, indicating worse clinical stages. High expression levels of PLOD family genes were associated with worse disease-free survival and distant metastasis-free survival, while high expression levels of PLOD1 and PLOD3 were related to worse overall survival in all breast cancer patients. The levels of PLOD family genes were all significantly higher in the age ≤51 y group, HR-negative patients, and triple negative breast cancer (TNBC) patients. They are associated with tumor-infiltrating immune cells (TIICs), including CD4+ T cells, CD8+ T cells, B cells, macrophages, neutrophils, and dendritic cells. According to co-expression gene analysis and functional enrichment, they are associated with protein hydroxylation, collagen biosynthesis and modifying enzymes, collagen metabolism, RNA splicing, extracellular matrix organization, VEGFA-VEGFR2 signaling pathway, and skeletal system development. Immunohistochemistry showed that the expressions of all PLOD family genes were significantly elevated in breast cancer tissues. PLOD1 expression was positively correlated with ER, TNBC status, and tumor grade. PLOD2 expression was positively connected with Ki-67 status. PLOD3 expression was positively related with age and tumor grade. CONCLUSIONS: PLOD family genes are novel potential prognostic biomarkers for breast cancer, and targeting PLOD inhibitors might be an effective strategy for breast cancer therapy.
Subject(s)
Breast Neoplasms , Gene Expression Regulation, Neoplastic , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase , Humans , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/metabolism , Female , Breast Neoplasms/genetics , Breast Neoplasms/immunology , Breast Neoplasms/mortality , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Prognosis , Middle Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolismABSTRACT
Visual object tracking often faces challenges such as invalid targets and decreased performance in low-light conditions when relying solely on RGB image sequences. While incorporating additional modalities like depth and infrared data has proven effective, existing multimodal imaging platforms are complex and lack real-world applicability. In contrast, near-infrared (NIR) imaging, commonly used in surveillance cameras, can switch between RGB and NIR based on light intensity. However, tracking objects across these heterogeneous modalities poses significant challenges, particularly due to the absence of modality switch signals during tracking. To address these challenges, we propose an adaptive cross-modal object tracking algorithm called modality-aware fusion network (MAFNet). MAFNet efficiently integrates information from both RGB and NIR modalities using an adaptive weighting mechanism, effectively bridging the appearance gap and enabling a modality-aware target representation. It consists of two key components: an adaptive weighting module and a modality-specific representation module. The adaptive weighting module predicts fusion weights to dynamically adjust the contribution of each modality, while the modality-specific representation module captures discriminative features specific to RGB and NIR modalities. MAFNet offers great flexibility as it can effortlessly integrate into diverse tracking frameworks. With its simplicity, effectiveness, and efficiency, MAFNet outperforms state-of-the-art methods in cross-modal object tracking. To validate the effectiveness of our algorithm and overcome the scarcity of data in this field, we introduce CMOTB, a comprehensive and extensive benchmark dataset for cross-modal object tracking. CMOTB consists of 61 categories and 1000 video sequences, comprising a total of over 799K frames. We believe that our proposed method and dataset offer a strong foundation for advancing cross-modal object-tracking research. The dataset, toolkit, experimental data, and source code will be publicly available at: https://github.com/mmic-lcl/ Datasets-and-benchmark-code.
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Quantitative analysis of activated neurons in mouse brains by a specific stimulation is usually a primary step to locate the responsive neurons throughout the brain. However, it is challenging to comprehensively and consistently analyze the neuronal activity trace in whole brains of a large cohort of mice from many terabytes of volumetric imaging data. Here, we introduce NEATmap, a deep learning-based high-efficiency, high-precision and user-friendly software for whole-brain neuronal activity trace mapping by automated segmentation and quantitative analysis of immunofluorescence labeled c-Fos+ neurons. We applied NEATmap to study the brain-wide differentiated neuronal activation in response to physical and psychological stressors in cohorts of mice.
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BACKGROUND: The use of adaptive designs in cancer trials has considerably increased worldwide in recent years, along with the release of various guidelines for their application. This systematic review aims to comprehensively summarize the key methodological and executive features of adaptive designs in cancer clinical trials. METHODS: A comprehensive search from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted to screen eligible clinical trials that employed adaptive designs and were conducted in cancer patients. The methodological and executive characteristics of adaptive designs were the main measurements extracted. Descriptive analyses, primarily consisting of frequency and percentage, were employed to analyzed and reported the data. RESULTS: A total of 180 cancer clinical trials with adaptive designs were identified. The first three most common type of adaptive design was the group sequential design (n=114, 63.3â¯%), adaptive dose-finding design (n=22, 12.2â¯%), and adaptive platform design (n=16, 8.9â¯%). The results showed that 4.4â¯% (n=8) of trials conducted post hoc modifications, and around 29.4â¯% (n=53) did not provide the methods for controlling type I errors. Among phase II or above trials, 79.9â¯% (112/140) applied the surrogate endpoint as the primary outcome in these trials. Importantly, 27.2â¯% (49/180) of trials did not report clear information on the independent data monitoring committee (iDMC), and 13.3â¯% (n=24) without clear information on interim analyses. Interim analyses suggested 34.4â¯% (62/180) of trials being stopped for futility, 10.6â¯% (n=19) for efficacy, and 2.2â¯% (n=4) for safety concerns in the early stage. CONCLUSIONS: This study emphasizes adaptive designs in cancer trials face significant challenges in their design or strict implementation according to protocol, which might significantly compromise the validity and integrity of trials. It is thus important for researchers, sponsors, and policymakers to actively oversee and guide their application.
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Clinical Trials as Topic , Neoplasms , Research Design , Humans , Neoplasms/therapy , Neoplasms/drug therapyABSTRACT
The copy number of genes in chromosomes can be modified by chromosomal integration to construct efficient microbial cell factories but the resulting genetic systems are prone to failure or instability from triggering homologous recombination in repetitive DNA sequences. Finding the optimal copy number of each gene in a pathway is also time and labor intensive. To overcome these challenges, we applied a multiple nonrepetitive coding sequence calculator that generates sets of coding DNA sequence (CDS) variants. A machine learning method was developed to calculate the optimal copy number combination of genes in a pathway. We obtained an engineered Yarrowia lipolytica strain for eicosapentaenoic acid biosynthesis in 6 months, producing the highest titer of 27.5 g l-1 in a 50-liter bioreactor. Moreover, the lycopene production in Escherichia coli was also greatly improved. Importantly, all engineered strains of Y. lipolytica, E. coli and Saccharomyces cerevisiae constructed with nonrepetitive CDSs maintained genetic stability.
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Base editors (BEs) are a recent generation of genome editing tools that couple a cytidine or adenosine deaminase activity to a catalytically impaired Cas9 moiety (nCas9) to enable specific base conversions at the targeted genomic loci. Given their strong application potential, BEs are under active developments toward greater levels of efficiency and safety. Here, a previously overlooked nCas9-centric strategy is explored for enhancement of BE. Based on a cytosine BE (CBE), 20 point mutations associated with nCas9-target interaction are tested. Subsequently, from the initial positive X-to-arginine hits, combinatorial modifications are applied to establish further enhanced CBE variants (1.1-1.3). Parallel nCas9 modifications in other versions of CBEs including A3A-Y130F-BE4max, YEE-BE4max, CGBE, and split-AncBE4max, as well as in the context of two adenine BEs (ABE), likewise enhance their respective activities. The same strategy also substantially improves the efficiencies of high-fidelity nCas9/BEs. Further evidence confirms that the stabilization of nCas9-substrate interactions underlies the enhanced BE activities. In support of their translational potential, the engineered CBE and ABE variants respectively enable 82% and 25% higher rates of editing than the controls in primary human T-cells. This study thus demonstrates a highly adaptable strategy for enhancing BE, and for optimizing other forms of Cas9-derived tools.
Subject(s)
CRISPR-Associated Protein 9 , CRISPR-Cas Systems , Gene Editing , Gene Editing/methods , Humans , CRISPR-Cas Systems/genetics , CRISPR-Associated Protein 9/genetics , CRISPR-Associated Protein 9/metabolism , HEK293 CellsABSTRACT
BACKGROUND: Protein residue-residue distance maps are used for remote homology detection, protein information estimation, and protein structure research. However, existing prediction approaches are time-consuming, and hundreds of millions of proteins are discovered each year, necessitating the development of a rapid and reliable prediction method for protein residue-residue distances. Moreover, because many proteins lack known homologous sequences, a waiting-free and alignment-free deep learning method is needed. RESULT: In this study, we propose a learning framework named FreeProtMap. In terms of protein representation processing, the proposed group pooling in FreeProtMap effectively mitigates issues arising from high-dimensional sparseness in protein representation. In terms of model structure, we have made several careful designs. Firstly, it is designed based on the locality of protein structures and triangular inequality distance constraints to improve prediction accuracy. Secondly, inference speed is improved by using additive attention and lightweight design. Besides, the generalization ability is improved by using bottlenecks and a neural network block named local microformer. As a result, FreeProtMap can predict protein residue-residue distances in tens of milliseconds and has higher precision than the best structure prediction method. CONCLUSION: Several groups of comparative experiments and ablation experiments verify the effectiveness of the designs. The results demonstrate that FreeProtMap significantly outperforms other state-of-the-art methods in accurate protein residue-residue distance prediction, which is beneficial for lots of protein research works. It is worth mentioning that we could scan all proteins discovered each year based on FreeProtMap to find structurally similar proteins in a short time because the fact that the structure similarity calculation method based on distance maps is much less time-consuming than algorithms based on 3D structures.
Subject(s)
Proteins , Proteins/chemistry , Computational Biology/methods , Databases, Protein , Protein Conformation , Algorithms , Sequence Analysis, Protein/methods , Neural Networks, ComputerABSTRACT
BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.