The L-shape relationship between hemoglobin, albumin, lymphocyte, platelet score and the risk of diabetic retinopathy in the US population.

Background: The primary aim of this study was to investigate the correlation between diabetic retinopathy (DR) and the HALP score (hemoglobin, albumin, lymphocyte, and platelet) in individuals with diabetes within the United States population. Methods: This cross-sectional investigation was based on the National Health and Nutrition Examination Survey (NHANES) database from 2003-2018. The following module calculated the HALP score: HALP score = [lymphocytes (/L) × hemoglobin (g/L) × albumin (g/L)]/platelets (/L). By performing the receiver operating characteristic (ROC) analysis, the optimal cutoff value of HALP was ascertained. Restricted cubic splines (RCS), multivariable logistic regression analysis, sensitivity analysis, and subgroup analysis were conducted to evaluate the effect of the HALP score on DR patients. Finally, the decision curve analysis (DCA) and clinical impact curve (CIC) were conducted to estimate the predictive power and clinical utility of the HALP score with clinical indicators. Results: According to the cutoff value (42.9) determined by the ROC curve, the participants were stratified into a lower HALP group (HALPlow) and a higher HALP group (HALPhigh). An L-shaped relationship between HALP score and DR risk was presented in the RCS model (P for nonlinearity <0.001). The DR risk sharply decreased with the increase of HALP, and the decline reached a plateau when HALP was more than 42.9. After fully adjustment, the multivariate logistic regression analysis found that HALPlow was an independent risk factor for DR (OR = 1.363, 95% CI: 1.111-1.671, P < 0.001). Besides, sensitivity analysis showed consistent results. Furthermore, the combination of HALP score and clinical indicators demonstrated predictive power and clinical utility, as shown by the ROC curve, DCA, and CIC. Conclusion: The HALP score has an L-shaped correlation with the risk of DR, and thus, the HALP score may contribute to the timely intervention of diabetes patients.

Predicting Natural Evolution in the RBD Region of the Spike Glycoprotein of SARS-CoV-2 by Machine Learning.

Machine learning (ML) is a key focus in predicting protein mutations and aiding directed evolution. Research on potential virus variants is crucial for vaccine development. In this study, the machine learning software PyPEF was employed to conduct mutation analysis within the receptor-binding domain (RBD) of the Spike glycoprotein of SARS-CoV-2. Over 48,960,000 variants were predicted. Eight prospective variants that could surface in the future underwent modeling and molecular dynamics simulations. The study forecasts that the latest variant, ISOY2P5O1, may potentially emerge around 17 November 2023, with an approximate window of uncertainty of ±22 days. The ISOY8P5O2 variant displayed an increased binding capacity in the dry assay, with a total predicted binding energy of -110.306 kcal/mol. This represents an 8.25% enhancement in total binding energy compared to the original SARS-CoV-2 strain discovered in Wuhan (-101.892 kcal/mol). Reverse research confirmed the structural significance of mutation sites using ML models, particularly in the context of protein folding. The study validated regression methods (SVR, RF, and PLS) with different data structures. This study investigates the effectiveness of the "ML-Guided Design Correctly Predicts Combinatorial Effects Strategy" compared to the "ML-Guided Design Correctly Predicts Natural Evolution Prediction Strategy". To enhance machine learning, we created a timestamping algorithm and two auxiliary programs using advanced techniques to rapidly process extensive data, surpassing batch sequencing capabilities. This study not only advances machine learning in guiding protein evolution but also holds potential for forecasting future viruses and vaccine development.

Predicting Alu exonization in the human genome with a deep learning model.

Alu exonization, or the recruitment of intronic Alu elements into gene sequences, has contributed to functional diversification; however, its extent and the ways in which it influences gene regulation are not fully understood. We developed an unbiased approach to predict Alu exonization events from genomic sequences implemented in a deep learning model, eXAlu, that overcomes the limitations of tissue or condition specificity and the computational burden of RNA-seq analysis. The model captures previously reported characteristics of exonized Alu sequences and can predict sequence elements important for Alu exonization. Using eXAlu, we estimate the number of Alu elements in the human genome undergoing exonization to be between 55-110K, 11-21 fold more than represented in the GENCODE gene database. Using RT-PCR we were able to validate selected predicted Alu exonization events, supporting the accuracy of our method. Lastly, we highlight a potential application of our method to identify polymorphic Alu insertion exonizations in individuals and in the population from whole genome sequencing data.

The effectiveness of ultrasound-guided injection of BTX-A in the management of sialorrhea in neurogenic dysphagia patients.

Objective: To evaluate the effectiveness of ultrasound-guided injection of botulinum toxin type A (BTX-A) in treating sialorrhea. Methods: We recruited 32 sialorrhea subjects and they received an ultrasound-guided injection of BTX-A. The extent of salivation was evaluated according to the Visual Analog Scale (VAS), Drooling Severity and Frequency Scale (DSFS), and Saliva Flow Rate (SFR). Laryngeal secretions were evaluated based on Fiberoptic Endoscopic Evaluation of Swallowing (FEES) rated according to the Murray Secretion Scale (MSS). We assessed the extent of salivation and laryngeal secretions before injection and at 1, 2, and 4 weeks after injection. Results: The scores for the VAS, DSFS-S, DSFS-F, and DSFS-T decreased significantly at 1, 2, and 4 weeks after injection compared with before injection (p < .05). Based on VAS, the efficacy was substantially higher at 2 and 4 weeks after injection than at 1 week after injection (p < .05). According to DSFS-S and DSFS-T, the efficacy was significantly higher at 4 weeks than at 1 week after injection (p < .05). The SFR and MSS scores at 1 and 2 weeks after injection were superior to those before injection (p < .05). Meanwhile, the SFR score 2 weeks after injection was superior to that 1 week after injection (p < .05). Conclusion: The ultrasound-guided injection of BTX-A can effectively reduce saliva secretion in patients with neurogenic dysphagia. Furthermore, it has the advantages of early onset time and lasting curative effects, which indicates that clinical promotion and application of this technique are justified. Level of Evidence: Level 3.

Focalizing regions of biomarker relevance facilitates biomarker prediction on histopathological images.

Image-based AI has thrived as a potentially revolutionary tool for predicting molecular biomarker statuses, which aids in categorizing patients for appropriate medical treatments. However, many methods using hematoxylin and eosin-stained (H&E) whole-slide images (WSIs) have been found to be inefficient because of the presence of numerous uninformative or irrelevant image patches. In this study, we introduced the region of biomarker relevance (ROB) concept to identify the morphological areas most closely associated with biomarkers for accurate status prediction. We actualized this concept within a framework called saliency ROB search (SRS) to enable efficient and effective predictions. By evaluating various lung adenocarcinoma (LUAD) biomarkers, we showcased the superior performance of SRS compared to current state-of-the-art AI approaches. These findings suggest that AI tools, built on the ROB concept, can achieve enhanced molecular biomarker prediction accuracy from pathological images.

Characteristics of post-stroke dysphagia: A retrospective study based on FEES.

OBJECTIVE: This study aims to examine the characteristics of dysphagia in stroke patients with different lesion sites and explore the factors that impact the duration of nasogastric tube after post-stroke dysphagia (PSD). METHODS: Patients with PSD were screened for analysis. Stroke types and lesion sites were confirmed using MRI or CT scans. Included patients were categorized into two groups: supratentorial stroke group (including lobar and deep intracerebral stroke subgroups) and infratentorial stroke group (including brainstem and cerebellar stroke subgroups). Fiberoptic endoscopic evaluation of swallowing (FEES), Penetration-aspiration scale (PAS), Yale pharyngeal residue (PR) severity rating scale, Functional oral intake scale (FOIS), Murray secretion severity rating scale (MSS), laryngopharyngeal sensation, and vocal fold mobility were investigated to assess the swallowing function. RESULTS: A total of 94 patients were included in the final analysis. Significant differences were found in PR scores (p < .001), PAS scores (p < .05), MSS scores (p < .05), and vocal fold mobility (p < .001) between infratentorial and supratentorial stroke groups. Moreover, lobar stroke showed significantly higher PR scores compared to the deep intracerebral stroke group (p < .05). Kaplan-Meier survival analysis indicated significant differences in the duration of nasogastric tube placement among the following groups: infratentorial versus supratentorial stroke, PAS ≤ 5 versus PAS > 5, PR ≥ 3 versus PR < 3, and normal vocal fold mobility versus vocal fold motion impairment group (p < .05). CONCLUSIONS: The infratentorial stroke may lead to worse swallowing function as compared to a supratentorial stroke. Additionally, patients with infratentorial stroke, PAS > 5, PR ≥ 3, or vocal fold motion impairment may contribute to a longer duration of nasogastric tube placement.

Effect of Modified Pharyngeal Electrical Stimulation on Patients with Severe Chronic Neurogenic Dysphagia: A Single-Arm Prospective Study.

Current treatments for severe chronic neurogenic dysphagia (SCND) are limited. Modified pharyngeal electrical stimulation (mPES) was modified from pharyngeal electrical stimulation (PES). This prospective study aimed to explore the efficacy and safety of mPES on SCND. 30 patients with severe chronic neurogenic dysphagia were recruited. mPES was administered to patients once daily until the functional oral intake scale score (FOIS) reach 3. Videofluoroscopic swallow study (VFSS), flexible endoscopic evaluation of swallowing (FEES), and high-resolution manometry (HRM) were utilized for evaluating the swallowing function. After mPES, 24 of 30 patients (80%) reached the endpoint (FOIS = 3) (P < 0.001). 3 of 6 tracheotomized patients (50%) removed the tracheal tube. The median number of mPES sessions for the 24 patients who met the criteria was 28 (17, 38) and the median period was 43 (29, 63) days. Moreover, a significant increase was observed in hypopharyngeal peak pressure (P = 0.015), hypopharyngeal contraction duration (P = 0.023), velopharyngeal peak pressure (P = 0.044), and velopharyngeal contraction duration (P = 0.031). A reduction was observed in PAS (P < 0.001), secretion (P = 0.001), vallecular residue (P < 0.001), left (P = 0.001), and right (P < 0.001) pyriform sinus residue. The median FOIS of 30 patients at 3-month follow-up was 5 (3, 6). No serious side effects were reported. mPES is a promising effective and safe therapeutic approach that is simple to use in patients with SCND.

Characteristics of dysphagia among different lesion sites of stroke: A retrospective study.

Objective: This study aims to compare the characteristics of dysphagia among different lesion sites and explore the possible risk factors that are relevant to penetration and aspiration after stroke. Materials and methods: Data on patients with post-stroke dysphagia were collected. Major measures of the videofluoroscopic swallowing study included pharyngeal transit duration (PTD), pharyngeal response duration (PRD), soft palate elevation duration (SED), stage transition duration (STD), hyoid bone anterior-horizontal displacement (HAD), hyoid bone superior-horizontal displacement (HSD), upper esophageal sphincter opening (UESO), Pharyngeal Residual Grade (PRG), and Penetration Aspiration Scale (PAS). Included patients were divided into supratentorial (deep or lobar intracerebral) and infratentorial stroke groups. The Kruskal-Wallis test, Spearman's correlation analysis, and multivariate logistic regression analyses were used to test the difference and the correlation between those measures. Time-to-event endpoints (oral feeding) were analyzed by the Kaplan-Meier method. Results: A total of 75 patients were included in this study. Significant differences were demonstrated in PTD, PRD, SED, STD, HAD, HSD, UESO, PAS, and PRG between supratentorial and infratentorial stroke groups (p < 0.05). The PRG score of the lobar intracerebral subgroup was significantly higher (p < 0.05) than that of the deep intracerebral and lobar + deep intracerebral stroke subgroups, while HSD was significantly shorter (p < 0.01). Spearman's correlation analysis revealed that PAS was related to PTD, PRG, HAD, and UESO (p < 0.05). Multivariate logistic regression analysis demonstrated that HAD and PRG may be risk factors for penetration and aspiration (p < 0.05). Kaplan-Meier survival plot showed that there was a significant difference in time to oral feeding between supratentorial and infratentorial stroke groups (p < 0.01). Conclusion: Infratentorial stroke may lead to worse swallowing function as compared with supratentorial stroke, and lobar intracerebral stroke may be worse than deep intracerebral stroke. Suitable preventive measures may be considered for patients with higher PRG scores and shorter HSD to avoid penetration and aspiration.

Botulinum toxin injection combined with traditional swallowing rehabilitation improved cricopharyngeal dysfunction in neuromyelitis optica spectrum disorder: A case report.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune diseases of the central nervous system, and often influence optic nerve and medulla oblongata. Previous studies found out that brain abnormalities were not rare in these patients. Medulla oblongata (MO) was commonly involved and usually located at dorsal part. Patients who diagnosed NMOSD with MO lesions were more likely to have dysphagia. Previous reports indicated that the symptoms and signs of NMOSD patients could be controlled after immunosuppressive therapy. This patient was a 49-year-old Asian woman presented with recurrent vomiting and diagnosed NMOSD with MO involvement. However, after immunotherapy in other hospital, she still suffered from dysphagia. She then came to our department and completed videofluoroscopic swallowing study (VFSS) and high-resolution pharyngeal manometry (HRPM). Her UES was not opening with aspiration and the UES residue pressure was higher than normal range, we figured that she had cricopharyngeal (CP) dysfunction. Then the SLP gave her traditional treatment, including catheter balloon dilation. But she failed improvement after treatment for 2 weeks. Then the clinicians decided to inject botulinum toxin (BTX) into her CP muscles, which needed specific location and appropriate dosage. Her UES residue pressure decreased after three times BTX injection. During this time, her SLP adjusted the treatment strategies based on her VFSS and HRM results. Combined BTX injection with traditional treatment, she can now eat food orally without restrictions. This case report we presented can provide treatment strategies for similar patients with dysphagia.

Jutils: a visualization toolkit for differential alternative splicing events.

MOTIVATION: Gene alternative splicing plays an important role in development, tissue specialization and disease and differences in splicing patterns can reveal important factors for phenotypic differentiation. While multiple computational methods exist to determine splicing differences, there is a need for user-friendly visualizations that present an intuitive view of the data and work across methods. RESULTS: We developed a toolkit, Jutils, for visualizing differential splicing events at the intron (splice junction) level. Jutils is method-agnostic, converting individual tools' output into a unified representation and using it to create visualizations. Jutils creates three types of visualizations, namely heatmaps of absolute and Z-score normalized splice ratios, sashimi plots and Venn diagrams of results from multiple comparisons. Jutils is lightweight, relying solely on the unified data file for visualizations. AVAILABILITY AND IMPLEMENTATION: Jutils is implemented in Python and is available from https://github.com/Splicebox/Jutils.

[Treatment of sacroiliac joint dislocation by Zhuang medicine tendon therapy combined with chiropractic manipulation].

OBJECTIVE: To analyze the clinical effect of Zhuang medicine tendon therapy combined with chiropractic manipulation in treating sacroiliac joint dislocation. METHODS: From January 2017 to May 2018, 60 patients with sacroiliac joint dislocation were divided into treatment group and control group according to the order of admission. There were 19 males and 11 females in the treatment group, aged from 23 to 52 (38.97±3.23) years old, with a course of 2 h to 5.1 months, with an average of (2.19±1.12) months. There were 14 males and 16 females in the control group, aged from 26 to 50 (39.07±3.30) years old, with a course of 3 h to 6 months, with an average of(2.41±1.05) months. The treatment group was treated with Zhuang medicine tendon therapy combined with chiropractic manipulation, while the control group was treated with conventional acupuncture and massage. Before treatment, the main clinical symptoms of the patients were lumbosacral pain, posterior superior iliac spine not at the same level and accompanied with dyskinesia. The pelvic separation test and the "4" test were positive. After treatment, the curative effect was evaluated according to the improved Macnab standard and the "score of treatment of lumbar diseases". RESULTS: Sixty patients were followed up for an average of 8 months. At the latest follow-up, the clinical effect of modified Macnab was better in the treatment group than in the control group(P<0.01). After treatment, the treatment group was better than the control group on lumbar function score (P<0.01). CONCLUSIONS: The treatment of sacroiliac joint dislocation by Zhuang medicine tendon therapy combined with chiropractic manipulation has good clinical effect and is worth further application and development.