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1.
Front Immunol ; 15: 1371764, 2024.
Article in English | MEDLINE | ID: mdl-38983858

ABSTRACT

Introduction: Environmental exposures and experimental manipulations can alter the ontogenetic composition of tissue-resident macrophages. However, the impact of these alterations on subsequent immune responses, particularly in allergic airway diseases, remains poorly understood. This study aims to elucidate the significance of modified macrophage ontogeny resulting from environmental exposures on allergic airway responses to house dust mite (HDM) allergen. Methods: We utilized embryonic lineage labeling to delineate the ontogenetic profile of tissue-resident macrophages at baseline and following the resolution of repeated lipopolysaccharide (LPS)-induced lung injury. We investigated differences in house dust mite (HDM)-induced allergy to assess the influence of macrophage ontogeny on allergic airway responses. Additionally, we employed single-cell RNA sequencing (scRNAseq) and immunofluorescent staining to characterize the pulmonary macrophage composition, associated pathways, and tissue localization. Results: Our findings demonstrate that the ontogeny of homeostatic alveolar and interstitial macrophages is altered after the resolution from repeated LPS-induced lung injury, leading to the replacement of embryonic-derived by bone marrow-derived macrophages. This shift in macrophage ontogeny is associated with reduced HDM-induced allergic airway responses. Through scRNAseq and immunofluorescent staining, we identified a distinct subset of resident-derived interstitial macrophages expressing genes associated with allergic airway diseases, localized adjacent to terminal bronchi, and diminished by prior LPS exposure. Discussion: These results suggest a pivotal role for pulmonary macrophage ontogeny in modulating allergic airway responses. Moreover, our findings highlight the implications of prior environmental exposures in shaping future immune responses and influencing the development of allergies. By elucidating the mechanisms underlying these phenomena, this study provides valuable insights into potential therapeutic targets for allergic airway diseases and avenues for further research into immune modulation and allergic disease prevention.


Subject(s)
Macrophages, Alveolar , Transcriptome , Animals , Mice , Macrophages, Alveolar/immunology , Macrophages, Alveolar/metabolism , Pyroglyphidae/immunology , Respiratory Hypersensitivity/immunology , Lung/immunology , Disease Models, Animal , Mice, Inbred C57BL , Allergens/immunology , Lipopolysaccharides , Female , Hypersensitivity/immunology
2.
Curr Oncol ; 31(6): 3161-3176, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38920723

ABSTRACT

BACKGROUND: Advanced non-small-cell lung cancer (NSCLC) can be treated with novel targeted therapies that are tailored to the genetic characteristics of malignancy. While tissue-based genomic testing is considered the gold standard for the detection of oncogenic driver mutations, several challenges like inadequate tissue availability, the invasiveness of procuring tumors, and prolonged turnaround time of analysis are encountered. Considering these limitations, guidelines have recognized liquid biopsies using circulating cell-free DNA (cfDNA) as a useful tool to complement conventional tissue testing. Even though cfDNA next-generation sequencing (NGS) can have high sensitivity and specificity, optimal patient benefit requires the interpretation of the molecular profiling results in the context of clinical and diagnostic features to achieve the best outcomes. CASE DESCRIPTIONS: In this case series, we present six patients with advanced NSCLC whose plasma or tissue biopsy samples were analyzed with commercially available comprehensive NGS assays that elucidate the role of testing at various time points in the treatment journey. In all six cases, comprehensive genomic profiling (CGP) provided clinically useful information to guide treatment decisions. CONCLUSION: Adding to the existing real-world evidence, this case series reinforces that CGP-driven treatment strategies in advanced NSCLC, coupled with other available clinical information, can optimize treatment decisions.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Female , Aged , High-Throughput Nucleotide Sequencing/methods , Genomics/methods
4.
Int J Surg ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833348

ABSTRACT

BACKGROUND: Insufficient evidence exists to ascertain the long-term prognosis in patients with obesity undergoing laparoscopic surgery versus open surgery for colorectal cancer. METHODS: Employing an institutional database from 2009 to 2019, we assessed individuals with a body mass index of ≥30 kg/m2 who underwent surgery for primary stage I-III colorectal adenocarcinoma. We used propensity score-weighted analysis to compare short-term and oncologic outcomes between laparoscopic and open surgical approaches. RESULTS: This study enrolled 473 patients (open vs. laparoscopic surgery: 220 vs. 253; median follow-up period, 60 mo). The laparoscopy group showed a significantly longer operative time (252 vs. 212 min), a higher anastomotic-leakage rate (5.14% vs. 0.91%), and a greater proportion of Clavien-Dindo class > III complications (5.93% vs. 1.82%). The open group showed a higher wound infection rate (7.27% vs. 3.16%) and a higher readmission rate (6.36% vs. 2.37%). After propensity-score weighting, laparoscopy was inferior to open surgery in terms of long-term overall survival (hazard ratio: 1.43), disease-free survival (1.39), and recurrence rate (21.1% vs. 14.5%). In the subgroup analysis, female patients, older individuals, stage III patients, patients with rectal cancer, and those who underwent surgery after 2014 showed inferior long-term outcomes after laparoscopy. CONCLUSIONS: Laparoscopic colorectal cancer surgery for patients with obesity requires significant caution. Despite good short-term outcomes, this procedure is associated with hidden risks and poor long-term prognoses. In female patients, older individuals, stage III patients, patients with rectal cancer, and those treated in the late surgery era subgroups, caution is advised when performing laparoscopic surgery.

5.
Front Immunol ; 15: 1372959, 2024.
Article in English | MEDLINE | ID: mdl-38690277

ABSTRACT

Introduction: Hypoxia is a common pathological driver contributing to various forms of pulmonary vascular diseases leading to pulmonary hypertension (PH). Pulmonary interstitial macrophages (IMs) play pivotal roles in immune and vascular dysfunction, leading to inflammation, abnormal remodeling, and fibrosis in PH. However, IMs' response to hypoxia and their role in PH progression remain largely unknown. We utilized a murine model of hypoxia-induced PH to investigate the repertoire and functional profiles of IMs in response to acute and prolonged hypoxia, aiming to elucidate their contributions to PH development. Methods: We conducted single-cell transcriptomic analyses to characterize the repertoire and functional profiles of murine pulmonary IMs following exposure to hypobaric hypoxia for varying durations (0, 1, 3, 7, and 21 days). Hallmark pathways from the mouse Molecular Signatures Database were utilized to characterize the molecular function of the IM subpopulation in response to hypoxia. Results: Our analysis revealed an early acute inflammatory phase during acute hypoxia exposure (Days 1-3), which was resolved by Day 7, followed by a pro-remodeling phase during prolonged hypoxia (Days 7-21). These phases were marked by distinct subpopulations of IMs: MHCIIhiCCR2+EAR2+ cells characterized the acute inflammatory phase, while TLF+VCAM1hi cells dominated the pro-remodeling phase. The acute inflammatory phase exhibited enrichment in interferon-gamma, IL-2, and IL-6 pathways, while the pro-remodeling phase showed dysregulated chemokine production, hemoglobin clearance, and tissue repair profiles, along with activation of distinct complement pathways. Discussion: Our findings demonstrate the existence of distinct populations of pulmonary interstitial macrophages corresponding to acute and prolonged hypoxia exposure, pivotal in regulating the inflammatory and remodeling phases of PH pathogenesis. This understanding offers potential avenues for targeted interventions, tailored to specific populations and distinct phases of the disease. Moreover, further identification of triggers for pro-remodeling IMs holds promise in unveiling novel therapeutic strategies for pulmonary hypertension.


Subject(s)
Gene Expression Profiling , Hypertension, Pulmonary , Hypoxia , Single-Cell Analysis , Transcriptome , Animals , Mice , Hypoxia/metabolism , Hypoxia/immunology , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/immunology , Hypertension, Pulmonary/genetics , Macrophages, Alveolar/immunology , Macrophages, Alveolar/metabolism , Mice, Inbred C57BL , Disease Models, Animal , Male , Lung/immunology , Lung/pathology , Lung/metabolism
6.
J Mol Graph Model ; 130: 108777, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38642500

ABSTRACT

This study delves into the prediction of protein-peptide interactions using advanced machine learning techniques, comparing models such as sequence-based, standard CNNs, and traditional classifiers. Leveraging pre-trained language models and multi-view window scanning CNNs, our approach yields significant improvements, with ProtTrans standing out based on 2.1 billion protein sequences and 393 billion amino acids. The integrated model demonstrates remarkable performance, achieving an AUC of 0.856 and 0.823 on the PepBCL Set_1 and Set_2 datasets, respectively. Additionally, it attains a Precision of 0.564 in PepBCL Set 1 and 0.527 in PepBCL Set 2, surpassing the performance of previous methods. Beyond this, we explore the application of this model in cancer therapy, particularly in identifying peptide interactions for selective targeting of cancer cells, and other fields. The findings of this study contribute to bioinformatics, providing valuable insights for drug discovery and therapeutic development.


Subject(s)
Computational Biology , Neural Networks, Computer , Peptides , Proteins , Peptides/chemistry , Proteins/chemistry , Computational Biology/methods , Humans , Machine Learning , Protein Binding , Binding Sites , Algorithms , Databases, Protein
7.
J Gastrointest Surg ; 28(3): 267-275, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38445919

ABSTRACT

BACKGROUND: Studies on prognostic factors for patients undergoing surgery to treat solitary liver metastases originating from colorectal cancer (CRC) are limited. This study aimed to analyze significant prognostic factors associated with tumor recurrence and long-term survival after liver resection for solitary colorectal liver metastasis. METHODS: Data from 230 patients with solitary liver metastases from CRC who received liver resection between 2010 and 2019 were retrospectively analyzed. Recurrence-free survival (RFS) and overall survival (OS) were accessed with the Kaplan-Meier method and log-rank test. Cox regression multivariate analysis identified independent variables associated with RFS and OS. Nomograms were developed to predict patient outcomes after surgery. RESULTS: The 3- and 5-year OS rates were 72.3% and 59.8%, respectively. The 3- and 5-year RFS rates were 40.0% and 27.1%, respectively. Multivariate analysis revealed age ≥ 70 years, resection margin width < 10 mm, initial N2 stage, hypoalbuminemia before surgery, and neutrophil-to-lymphocyte ratio (NLR) ≥ 3 after surgery as independent prognostic factors for OS. For RFS, initial N2 stage, hypoalbuminemia before surgery, NLR ≥ 3 after surgery, elevated carcinoembryonic antigen (CEA) levels after surgery, and CEA ratio (after/before liver resection) < 0.3 were identified as independent prognostic factors. CONCLUSION: This study demonstrated that initial N2 stage, hypoalbuminemia before liver resection, and NLR ≥ 3 after liver resection exert a significant association on the RFS and OS of patients undergoing surgery for solitary liver metastases from CRC. Thus, upfront chemotherapy, prompt postoperative chemotherapy, and intensive postoperative surveillance are mandatory for patients having these adverse factors.


Subject(s)
Colorectal Neoplasms , Hypoalbuminemia , Liver Neoplasms , Humans , Aged , Carcinoembryonic Antigen , Prognosis , Retrospective Studies , Liver Neoplasms/surgery
8.
Comput Biol Chem ; 110: 108055, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38555810

ABSTRACT

Accurate classification of membrane proteins like ion channels and transporters is critical for elucidating cellular processes and drug development. We present DeepPLM_mCNN, a novel framework combining Pretrained Language Models (PLMs) and multi-window convolutional neural networks (mCNNs) for effective classification of membrane proteins into ion channels and ion transporters. Our approach extracts informative features from protein sequences by utilizing various PLMs, including TAPE, ProtT5_XL_U50, ESM-1b, ESM-2_480, and ESM-2_1280. These PLM-derived features are then input into a mCNN architecture to learn conserved motifs important for classification. When evaluated on ion transporters, our best performing model utilizing ProtT5 achieved 90% sensitivity, 95.8% specificity, and 95.4% overall accuracy. For ion channels, we obtained 88.3% sensitivity, 95.7% specificity, and 95.2% overall accuracy using ESM-1b features. Our proposed DeepPLM_mCNN framework demonstrates significant improvements over previous methods on unseen test data. This study illustrates the potential of combining PLMs and deep learning for accurate computational identification of membrane proteins from sequence data alone. Our findings have important implications for membrane protein research and drug development targeting ion channels and transporters. The data and source codes in this study are publicly available at the following link: https://github.com/s1129108/DeepPLM_mCNN.


Subject(s)
Ion Channels , Neural Networks, Computer , Ion Channels/metabolism , Ion Channels/chemistry , Deep Learning , Ion Transport
9.
J Dent Sci ; 19(1): 637-639, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38303790

ABSTRACT

The evaluation of dental malpractice claims database is helpful to analyze the risk and lower the chances of potential litigation. In this descriptive analysis, the Taiwan Judicial Judgment Database was used to analyze the civil court decisions of dental malpractice related to infection from January 1, 2000 to August 31, 2023. After rigor verdicts reviewed, 53 dental malpractice civil judgments related to infection were included and further analyzed. Total 15 lawsuits were required to recover the punitive damages. The overall civil conviction rate was 28.3%. Two cases occurred in the dental department at medical center and 13 cases were found in the local clinics. The top one awarded compensation is dental implant. The amount of compensation was ranged from NT$ 110,000 to NT$ 3,000,000. In conclusion, this analysis can provide the important information and reference in the amounts of compensation for dental malpractice in Taiwan.

10.
Microsurgery ; 44(1): e31041, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37009759

ABSTRACT

BACKGROUND: Arteriovenous (AV) looping prior to the lower extremity free flap reconstruction enables better venous drainage in flap circulation, leading to less flap complications and better survival. A two-staged reconstruction including free tissue transfer after AV looping ensures a robust venous drainage of the flap. Arterialization of the AV loop results in less venous problems after the free flap reconstruction. However, major problems of this staged operation include AV loop kinking, heavy compression and loop exposure, leading to AV graft failure and interruption of surgical planning. The purpose of this article is to summarize probable flaws we noticed in conventional two-stage lower limb reconstruction and overcome those problems using the skin paddle-containing vein graft. METHOD: Eight patients with lower limb defects underwent lower limb reconstruction surgery using this technique at our institute. The mean age was 52 years old. Of the eight patients, three of them have the defect due to infection. Three of them was due to trauma and three of them was due to full-thickness burn. Five of the defects located at foot. The other three defects located at heel, knee, and pretibial region. All of them require AV looping because of unavailability of nearby recipient vessels. They all received a two-stage operation, including the first stage AV looping with a skin paddle-containing vein graft and the second stage definite free tissue transfer. RESULTS: The mean defect size was 140 cm2 (72-225). The mean length of AV loops was 17.1 cm (8-25). The mean size of skin paddles for vein grafts was 19.4 cm2 (15-24). The mean size of free ALT flaps 154.4 cm2 (105-252). All eight patients experienced a smooth postoperative course with no major or minor complications. There were no graft thrombosis or graft rupture complications during the vascular maturation period. All eight AV loops survived during maturation. All eight patients progressed to the second stage surgery. Maturation time ranged from 5 to 7 days. Free ALT flap was employed during the second stage reconstruction. All flaps survived at the last follow-up visit. There was no partial flap loss and complications. The mean follow-up time was 12.25 months, ranging from 8 to 17 months. CONCLUSION: The skin paddle-containing vein graft is an effective modification of the regular vein graft for AV looping procedure. The skin paddle prevents the underlying AV loop from compression, kinking and twisting during maturation. It also aids assessing patency of the AV loop and avoids the formation of adhesion between the AV loop and the surrounding tissue.


Subject(s)
Free Tissue Flaps , Plastic Surgery Procedures , Soft Tissue Injuries , Humans , Middle Aged , Free Tissue Flaps/blood supply , Treatment Outcome , Skin Transplantation , Postoperative Complications/surgery , Lower Extremity/surgery , Soft Tissue Injuries/surgery
11.
Phys Ther ; 104(1)2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37883453

ABSTRACT

OBJECTIVE: The Movement Assessment Battery for Children-2 (MABC-2) is a popular assessment of children's motor skills in both Western and Eastern countries. Since children's motor skills are strongly influenced by the sociocultural context, it is essential to specifically examine the applicability of the MABC-2 in different cultures. The performance on the MABC-2 age band 1 of children in Taiwan was compared with the standardized sample from the United Kingdom. The sex differences in the performance on the MABC-2 were also investigated. METHODS: Children aged 3 to 6 years were recruited and categorized into 4 age groups. The researchers assessed the children with the MABC-2 age band 1, containing 8 tasks categorized into 3 components: manual dexterity, aiming and catching, and balance. Z tests and effect sizes were used to examine the cultural differences in the 3 components and in the total scale of the MABC-2. Independent t tests were used to check for sex differences in the MABC-2. RESULTS: Data on 615 children with a mean age of 4.95 years (SD = 0.97) were collected. Clinically significant differences (effect size > 0.5) were found in 2 components and the total scale of the MABC-2 across most age groups. Children in Taiwan performed better on manual dexterity, balance, and the total scale. Marginally clinically significant differences (absolute effect size > 0.4) were found in the aiming and catching component for the children aged 3 and 6 years old; children in Taiwan scored lower on aiming and catching than did children in the United Kingdom. Girls had significantly higher scores on manual dexterity, balance, and the total scale, while boys had significantly higher scores on aiming and catching. CONCLUSIONS: Cultural and sex differences exist in the MABC-2. Constructing a norm for children in Taiwan of different sex and modification of the items are suggested for application of the MABC-2 in Taiwan.


Subject(s)
Cross-Cultural Comparison , Motor Skills Disorders , Child , Humans , Male , Female , Child, Preschool , Taiwan , Motor Skills , Movement
12.
Int J Cardiovasc Imaging ; 40(2): 425-439, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37902921

ABSTRACT

Pulmonary arterial stiffness (PAS) is a pathologic hallmark of all types of pulmonary hypertension (PH). Cardiac MRI (CMR), a gold-standard imaging modality for the evaluation of pulmonary flow, biventricular morphology and function has been historically reserved for the longitudinal clinical follow-up, PH phenotyping purposes, right ventricular evaluation, and research purposes. Over the last two decades, numerous indices combining invasive catheterization and non-invasive CMR have been utilized to phenotype the character and severity of PAS in different types of PH and to assess its clinically prognostic potential with encouraging results. Many recent studies have demonstrated a strong role of CMR derived PAS markers in predicting long-term clinical outcomes and improving currently gold standard risk assessment provided by the REVEAL calculator. With the utilization of a machine learning strategies, strong diagnostic and prognostic performance of CMR reported in multicenter studies, and ability to detect PH at early stages, the non-invasive assessment of PAS is on verge of routine clinical utilization. In this review, we focus on appraising important CMR studies interrogating PAS over the last 20 years, describing the benefits and limitations of different PAS indices, and their pathophysiologic relevance to pulmonary vascular remodeling. We also discuss the role of CMR and PAS in clinical surveillance and phenotyping of PH, and the long-term future goal to utilize PAS as a biomarker to aid with more targeted therapeutic management.


Subject(s)
Hypertension, Pulmonary , Vascular Stiffness , Humans , Cardiac Catheterization/methods , Predictive Value of Tests , Pulmonary Artery , Magnetic Resonance Imaging , Hypertension, Pulmonary/diagnostic imaging , Ventricular Function, Right
14.
Am J Ophthalmol ; 257: 143-153, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37482371

ABSTRACT

PURPOSE: To summarize key findings from a Cochrane review of the benefits and safety of antibiotic therapy compared with placebo (or vehicle) for acute bacterial conjunctivitis. DESIGN: Systematic review and meta-analysis. METHODS: We included placebo-controlled randomized controlled trials (RCTs) that compared topical antibiotics with placebo. We followed Cochrane methods for trial selection, data extraction, risk of bias assessment, and evidence synthesis. RESULTS: Twenty-one RCTs involving 8805 participants with acute bacterial conjunctivitis were included. Fifteen (71%) RCTs examined fluoroquinolone (FQ) drops, 3 tested macrolides, alone or in combination with steroids, and another 3 compared other non-FQ antibiotics. Intention-to-treat estimates suggested that compared with placebo, antibiotics may increase clinical recovery by 26% (risk ratio [RR]: 1.26; 95% confidence interval [CI]: 1.09-1.46) at the end of therapy (5 RCTs, 1474 participants). Modified intention-to-treat estimates, in which only participants with laboratory-confirmed bacterial conjunctivitis were analyzed, indicated that antibiotics were associated with 53% higher likelihood of microbiological cure as compared with placebo (RR: 1.53; 95% CI: 1.34-1.74; 10 RCTs, 2827 participants). Non-FQs (RR: 4.05; 95% CI: 1.36-12.00), but not FQs (RR: 0.70; 95% CI: 0.54-0.90), were likely to increase treatment-associated ocular complications such as eye pain, discomfort, and allergic reactions; the certainty of level of evidence was very low. CONCLUSIONS: Moderate level certainty of evidence suggested that antibiotics may increase the likelihood of clinical recovery and microbiological clearance compared with placebo. Very low-level certainty of evidence suggested that antibiotics may be associated with potential harm in patients with acute bacterial conjunctivitis, but the potential risk of bias from study design, inconsistency in outcome measurement, and reporting limit the evidence to very low certainty.


Subject(s)
Anti-Bacterial Agents , Conjunctivitis, Bacterial , Humans , Anti-Bacterial Agents/therapeutic use , Conjunctivitis, Bacterial/drug therapy
16.
Methods ; 220: 11-20, 2023 12.
Article in English | MEDLINE | ID: mdl-37871661

ABSTRACT

Secondary active transporters play pivotal roles in regulating ion and molecule transport across cell membranes, with implications in diseases like cancer. However, studying transporters via biochemical experiments poses challenges. We propose an effective computational approach to identify secondary active transporters from membrane protein sequences using pre-trained language models and deep learning neural networks. Our dataset comprised 290 secondary active transporters and 5,420 other membrane proteins from UniProt. Three types of features were extracted - one-hot encodings, position-specific scoring matrix profiles, and contextual embeddings from the ProtTrans language model. A multi-window convolutional neural network architecture scanned the ProtTrans embeddings using varying window sizes to capture multi-scale sequence patterns. The proposed model combining ProtTrans embeddings and multi-window convolutional neural networks achieved 86% sensitivity, 99% specificity and 98% overall accuracy in identifying secondary active transporters, outperforming conventional machine learning approaches. This work demonstrates the promise of integrating pre-trained language models like ProtTrans with multi-scale deep neural networks to effectively interpret transporter sequences for functional analysis. Our approach enables more accurate computational identification of secondary active transporters, advancing membrane protein research.


Subject(s)
Deep Learning , Membrane Proteins , Neural Networks, Computer , Machine Learning , Amino Acid Sequence
17.
Am J Occup Ther ; 77(5)2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37824724

ABSTRACT

IMPORTANCE: Performance of coloring, origami, and copying activities reflects children's visual-motor integration (VMI), but the levels of association remain unclear. OBJECTIVE: To use artificial intelligence (AI) to investigate associations of performance of coloring, origami, and copying activities with VMI. DESIGN: Cross-sectional study. SETTING: Kindergartens. PARTICIPANTS: A sample of 370 children (182 boys and 188 girls) in the second and third years of kindergarten. OUTCOMES AND MEASURES: Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition (VMI-6). RESULTS: Data for preschool children from an ongoing project were retrieved. AI models were trained to use photographs of activity products to predict total score on the VMI-6. R2 values were used to identify the variance in VMI-6 standardized scores explained by predicted scores from the activities. That is, R2 values reflected associations between activity performance and VMI. The R2 values for the combination of origami and copying were the largest (.390-.577). These R2 values were larger than those for each individual activity (.340-.473) and similar to those for the combination of all three activities (.400-.550). CONCLUSIONS AND RELEVANCE: Because moderate R2 values were found between performance of the three activity products and VMI, the three activities have high potential for use in identifying children's level of VMI or as teaching materials to facilitate the development of children's VMI. Furthermore, combining origami and copying activities is recommended for teachers and clinicians who need to address VMI. What This Article Adds: A combination of origami and copying activities had the strongest associations with children's VMI. Teachers and clinicians can use these two activities when addressing VMI development among preschool children.


Subject(s)
Artificial Intelligence , Child Development , Male , Female , Child, Preschool , Humans , Cross-Sectional Studies , Psychomotor Performance , Neuropsychological Tests
18.
Proteomics ; 23(23-24): e2200494, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37863817

ABSTRACT

Membrane proteins play a crucial role in various cellular processes and are essential components of cell membranes. Computational methods have emerged as a powerful tool for studying membrane proteins due to their complex structures and properties that make them difficult to analyze experimentally. Traditional features for protein sequence analysis based on amino acid types, composition, and pair composition have limitations in capturing higher-order sequence patterns. Recently, multiple sequence alignment (MSA) and pre-trained language models (PLMs) have been used to generate features from protein sequences. However, the significant computational resources required for MSA-based features generation can be a major bottleneck for many applications. Several methods and tools have been developed to accelerate the generation of MSAs and reduce their computational cost, including heuristics and approximate algorithms. Additionally, the use of PLMs such as BERT has shown great potential in generating informative embeddings for protein sequence analysis. In this review, we provide an overview of traditional and more recent methods for generating features from protein sequences, with a particular focus on MSAs and PLMs. We highlight the advantages and limitations of these approaches and discuss the methods and tools developed to address the computational challenges associated with features generation. Overall, the advancements in computational methods and tools provide a promising avenue for gaining deeper insights into the function and properties of membrane proteins, which can have significant implications in drug discovery and personalized medicine.


Subject(s)
Algorithms , Membrane Proteins , Animals , Horses , Sequence Alignment , Amino Acid Sequence , Sequence Analysis, Protein , Computational Biology/methods
19.
Anal Chem ; 95(38): 14341-14349, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37715702

ABSTRACT

Reporter gene assays are essential for high-throughput analysis, such as drug screening or determining downstream signaling activation/inhibition. However, use of this technology has been hampered by the high cost of the substrate (e.g., d-Luciferin (d-Luc)) in the most common firefly luciferase (FLuc) reporter gene assay. Although alternate luciferase is available worldwide, its substrate has remained expensive, and a more affordable option is still in demand. Here, we present a membrane-tethered horseradish peroxidase (mHRP), a new reporter system composed of a cell membrane expressing HRP that can preserve its enzymatic function on the cell surface, facilitates contact with HRP substrates (e.g., ABTS and TMB), and avoids the cell lysis process and the use of the high-priced luciferase substrate. An evaluation of the light signal sensitivity of mHRP compared to FLuc showed that both had comparable signal sensitivity. We also identified an extended substrate half-life of more than 5-fold that of d-Luc. Of note, this strategy provided a more stable detection signal, and the cell lysis process is not mandatory. Furthermore, with this strategy, we decreased the total amount of time taken for analysis and increased the time of detection limit of the reporter assay. Pricing analysis showed a one-third to one twenty-eighth price drop per single test of reporter assay. Given the convenience and stability of the mHRP reporter system, we believe that our strategy is suitable for use as an alternative to the luciferase reporter assay.


Subject(s)
Biological Assay , Gene Expression Profiling , Membranes , Cell Membrane , Horseradish Peroxidase , Luciferases, Firefly/genetics
20.
BMC Cancer ; 23(1): 900, 2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37749535

ABSTRACT

BACKGROUND: Early-stage colorectal cancer had excellent outcomes after curative resection, typically. However, a perplexing survival paradox between stage II and stage III was noted. This paradox could be influenced by the administration of routine postoperative adjuvant chemotherapy and the presence of high-risk factors in stage II CRC. The objective of the study was to investigate the influence of high-risk factors on patients with stage II CRC and assess the efficacy of oral tegafur/uracil (UFT) plus leucovorin as adjuvant chemotherapy for stage II CRC patients. METHODS: A retrospective study was conducted using propensity score matching at a single medical institution. A total of 1544 patients with stage II colorectal cancer who underwent radical surgery between January 2004 and January 2009 were included. The intervention used was tegafur/uracil plus leucovorin as adjuvant chemotherapy. The main outcome measures were disease-free survival and overall survival. RESULTS: After propensity score matching, 261 patients were included in three groups: no-treatment, half-year treatment, and one-year treatment. The clinical characteristics of each group tended to be more consistent. The Cox proportional hazard models showed that tegafur/uracil treatment or not was a significant independent factor for oncological outcome. Kaplan-Meier analysis also showed significantly better disease-free survival and overall survival. Further investigation revealed that tegafur/uracil duration was an independent factor for oncological outcome. While the survival curve did not reach statistical significance, the one-year UFT treatment group demonstrated the best treatment trend. CONCLUSIONS: This study suggests that tegafur/uracil plus leucovorin is a feasible adjuvant chemotherapy regimen for patients with stage II colorectal cancer after curative surgical treatment. Prolonged tegafur/uracil plus leucovorin treatment for 12 months showed a trend towards better outcomes in patients with stage II colorectal cancer.


Subject(s)
Colorectal Neoplasms , Tegafur , Humans , Leucovorin , Taiwan , Retrospective Studies , Propensity Score , Treatment Outcome , Uracil , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/surgery , Chemotherapy, Adjuvant
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