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Machine Learning for Detecting Blood Transfusion Needs Using Biosignals
Adequate oxygen in red blood cells carrying through the body to the heart and brain is important to maintain life. For those patients requiring blood, blood transfusion is a common procedure in which donated blood or blood components are given through an intravenous line. However, detecting the need for blood transfusion is time-consuming and sometimes not easily diagnosed, such as internal bleeding. This study considered physiological signals such as electrocardiogram (ECG), photoplethysmogram (PPG), blood pressure, oxygen saturation (SpO2), and respiration, and proposed the machine learning model to detect the need for blood transfusion accurately. For the model, this study extracted 14 features from the physiological signals and used an ensemble approach combining extreme gradient boosting and random forest. The model was evaluated by a stratified five-fold cross-validation: the detection accuracy and area under the receiver operating characteristics were 92.7% and 0.977, respectively. © 2023 CRL Publishing. All rights reserved.ope
Effectiveness of Fluid and Caffeine Modifications on Symptoms in Adults With Overactive Bladder: A Systematic Review
Overactive bladder (OAB) is prevalent in men and women and negatively impacts physical and psychological health. Fluid and caffeine intake modifications, which are lifestyle modification interventions, are simple methods to manage OAB. Howev er, studies that synthesized both interventions and found scientific evidence are scarce. This review aimed to synthesize scien tific evidence on whether fluid and caffeine intake modifications are effective for OAB symptoms. PubMed, CINAHL (Cumu lative Index for Nursing and Allied Health Literature), Embase, Scopus, the Cochrane Library, KoreaMed, and RISS (Research Information Sharing Service) were used to search for studies and 8 studies were included. The Cochrane risk of bias tool (RoB 2.0) and ROBINS-I (Risk Of Bias In Non-randomized Studies - of Interventions) were used to assess the quality of selected studies. Due to the heterogeneous outcome variables, a meta-analysis was not conducted. Among the 8 included, 7 studies were randomized controlled trials and one was a quasi-experimental study. Four studies assessed urgency. Caffeine reduction was statistically effective for urgency symptoms, but increasing fluid intake was not. Frequency was assessed in 5 studies, which showed decreasing caffeine and fluid intake was effective in treating the symptoms. Urinary incontinence episodes were assessed in 6 studies, and nocturia in 2. Restricting caffeine intake was effective in treating these 2 symptoms, but restricting both caffeine and fluid intake was not. Quality of life (QoL) was examined in 5 studies, and modifying fluid and caffeine in take significantly improved QoL in 2. Although there were limited studies, our review provides scientific evidence that fluid and caffeine intake modification effectively manages OAB symptoms. Further research should examine acceptability and sus tainability of interventions in the long-term and enable meta-analysis.ope
Explainable deep learning-based clinical decision support engine for MRI-based automated diagnosis of temporomandibular joint anterior disk displacement
Background and Objective: MRI is considered the gold standard for diagnosing anterior disc displacement (ADD), the most common temporomandibular joint (TMJ) disorder. However, even highly trained clinicians find it difficult to integrate the dynamic nature of MRI with the complicated anatomical features of the TMJ. As the first validated study for MRI-based automatic TMJ ADD diagnosis, we propose a clinical decision support engine that diagnoses TMJ ADD using MR images and provides heat maps as the visualized rationale of diagnostic predictions using explainable artificial intelligence. Methods: The engine builds on two deep learning models. The first deep learning model detects a region of interest (ROI) containing three TMJ components (i.e., temporal bone, disc, and condyle) in the entire sagittal MR image. The second deep learning model classifies TMJ ADD into three classes (i.e., normal, ADD without reduction, and ADD with reduction) within the detected ROI. In this retrospective study, the models were developed and tested on the dataset acquired between April 2005 to April 2020. The additional independent dataset acquired at a different hospital between January 2016 to February 2019 was used for the external test of the classification model. Detection performance was assessed by mean average precision (mAP). Classification performance was assessed by the area under the receiver operating characteristic (AUROC), sensitivity, specificity, and Youden's index. 95% confidence intervals were calculated via non-parametric bootstrap to assess the statistical significance of model performances. Results: The ROI detection model achieved mAP of 0.819 at 0.75 intersection over union (IoU) thresholds in the internal test. In internal and external tests, the ADD classification model achieved AUROC values of 0.985 and 0.960, sensitivities of 0.950 and 0.926, and specificities of 0.919 and 0.892, respectively. Conclusions: The proposed explainable deep learning-based engine provides clinicians with the predictive result and its visualized rationale. The clinicians can make the final diagnosis by integrating primary diagnostic prediction obtained from the proposed engine with the patient's clinical examination findings. © 2023restrictio
Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesis
IntroductionAdministration of follicle-stimulating hormone (FSH) has been recommended to stimulate spermatogenesis in infertile men with hypogonadotropic hypogonadism, whose sperm counts do not respond to human chorionic gonadotropin alone. However, FSH has a short serum half-life requiring frequent administration to maintain its therapeutic efficacy. To improve its pharmacokinetic properties, we developed a unique albumin-binder technology, termed "anti-serum albumin Fab-associated" (SAFA) technology. We tested the feasibility of applying SAFA technology to create long-acting FSH as a therapeutic candidate for patients with hypogonadotropic hypogonadism. MethodsSAFA-FSH was produced using a Chinese hamster ovary expression system. To confirm the biological function, the production of cyclic AMP and phosphorylation of ERK and CREB were measured in TM4-FSHR cells. The effect of gonadotropin-releasing hormone agonists on spermatogenesis in a hypogonadal rat model was investigated. ResultsIn in vitro experiments, SAFA-FSH treatment increased the production of cyclic AMP and increased the phosphorylation of ERK and CREB in a dose-dependent manner. In animal experiments, sperm production was not restored by human chorionic gonadotropin treatment alone, but was restored after additional recombinant FSH treatment thrice per week or once every 5 days. Sperm production was restored even after additional SAFA-FSH treatment at intervals of once every 5 or 10 days. DiscussionLong-acting FSH with bioactivity was successfully created using SAFA technology. These data support further development of SAFA-FSH in a clinical setting, potentially representing an important advancement in the treatment of patients with hypogonadotropic hypogonadism.ope
The association between autoantibody types and salivary gland hypofunction in patients with primary Sjögren's syndrome
Background This study analyzed the association between autoantibody types and salivary gland hypofunction in patients with primary Sjogren's syndrome (pSS). Methods A retrospective analysis was performed on patients who visited the Department of Orofacial Pain and Oral Medicine at Yonsei University Dental Hospital from January 1, 2010 to May 31, 2021, and who were diagnosed with pSS. Out of 191 patients who fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria, 50 were positive for both anti-Ro/SSA and anti-La/SSB, whereas 97 had anti-Ro/SSA but not anti-La/SSB antibodies. Forty-four patients for whom neither anti-Ro/SSA nor anti-La/SSB antibodies were found were diagnosed with Sjogren's syndrome by minor salivary gland biopsy. Results The anti-Ro/SSA antibody-positive group showed higher rheumatoid factor (RF) levels than the anti-Ro/SSA antibody-negative group. The anti-La/SSB antibody-positive group showed lower unstimulated whole saliva (UWS), stimulated whole saliva (SWS), higher erythrocyte sedimentation rate and RF level than the anti-La/SSB antibody-negative group. In addition, the group with both anti-Ro/SSA and anti-La/SSB antibodies showed lower UWS than the group with only anti-Ro/SSA antibodies. However, there were no significant differences in UWS or SWS after taking pilocarpine, and C-reactive protein. Conclusions UWS and SWS were lower when a patient was positive for anti-La/SSB, showing that anti-La/SSB is more likely to be involved in salivary gland hypofunction than anti-Ro/SSA in patients with pSS. Therefore, performing laboratory tests, including anti-La/SSB, helps predict the prognosis of salivary gland function in patients with suspected pSS.restrictio
MicroRNA super-resolution imaging in blood for Alzheimer's disease
We propose a novel blood biomarker detection method thatuses miRNA super-resolution imaging to enable the early diagnosisof Alzheimer’s disease (AD). Here, we report a singlemoleculedetection method for visualizing disease-specificmiRNA in tissue from an AD mice model, and peripheral bloodmononuclear cells (PBMCs) from AD patients. Using optimizedMagnified Analysis of Proteome (MAPs), we confirmed that fivemiRNAs contribute to neurodegenerative disease in the brainhippocampi of 5XFAD and wild-type mice. We also assessedPBMCs isolated from the whole blood of AD patients and ahealthy control group, and subsequently analyzed those samplesusing miRNA super-resolution imaging. We detected moremiR-200a-3p expression in the cornu ammonis 1 and dentategyrus regions of 3 month-old 5XFAD mice than in wild-typemice. Additionally, miRNA super-resolution imaging of bloodprovides AD diagnosis platform for studying miRNA regulationinside cells at the single molecule level. Our results present apotential liquid biopsy method that could improve the diagnosisof early stage AD and other diseases.ope
Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease: A Randomized Clinical Trial
IMPORTANCE In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease.OBJECTIVE To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease.DESIGN, SETTING, AND PARTICIPANTS A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022).INTERVENTIONS Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg.MAIN OUTCOMES AND MEASURES Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points.RESULTS Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P < .001 for noninferiority).CONCLUSIONS AND RELEVANCE Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy.restrictio
Long-term results comparison after anterior cervical discectomy with BGS-7 spacer (NOVOMAX®-C) and allograft spacer: A prospective observational study
Introduction: In an anterior cervical discectomy and fusion (ACDF), various types of graft materials including autograft, allograft, and synthetic graft have been used to achieve adequate spinal fusion. Allograft spacer is mainly used in cervical fusion, especially in the anterior approach. The synthetic bone graft material BGS-7(CaO-SiO2-P2O5-B2O3, bioactive Glass-Ceramics) can bind with surrounding bone tissue by forming a hydroxyapatite layer bone bridge, leading to faster graft osseointegration. This study was conducted to compare long-term clinical outcome of BGS-7 spacer and allograft spacer for anterior cervical discectomy and fusion surgery.
Materials and Methods: From September 2014 to December 2016, Consecutive anterior cervical discectomy and fusion surgeries using a BGS-7 spacer (N = 18) and Allograft spacer (N = 26) were compared for postoperative clinical outcomes. Radiologic assessments were performed, and Instrumental failure, including breakage, cage migration, subsidence were observed and Fusion status were analyzed. Finite element analysis was performed for simulating mechanical stress between the vertebral body and implant. Clinical outcomes were evaluated using neck VAS, NDI, and JOA on the patient’s final follow-up visits.
Results: Among the 44 patients who underwent an anterior cervical discectomy and fusion surgery using the BGS-7 spacer and Allograft spacer, there were 30 men and 14 women. The average age at the operation was 47.69 ± 10.49 in allograft spacer and 51.67 ± 11.03 in BGS-7 spacer. The mean follow-up period was 89.18 ± 5.44 months. Twenty three (88.46%) patients in allograft spacer and 20(100%) patients in BGS-7 spacer were demonstrated radiologic evidence of interbody fusion in last OPD, which accounts for fusion grade 4 or 5. Peak stresses were 343.85 MPa in allograft spacer, and 132.55 MPa in BGS-7 spacer. Long-term clinical outcomes including neck VAS, NDI, and JOA didn’t show statistical differences between the two groups. There were no adverse events related to the BGS-7 spacer.10.3389/fbioe.2023.110046.
Conclusion: The BGS-7 spacer demonstrated reliability as a spacer in anterior cervical discectomy and fusionF surgery without instrumental failure. Early stabilization with a bony bridge formation was observed at the intermediate follow-up period, and the long-term clinical outcome was favorable at more than 60 months after surgery without any adverse events. Thus, the BGS-7 spacer is a safe and effective alternative to the allograft spacer in anterior cervical discectomy and fusion surgery.ope
Risk of systemic lupus erythematosus flares according to autoantibody positivity at the time of diagnosis
To estimate the risk of systemic lupus erythematosus (SLE) flares based on the autoantibody positivity at the time of SLE diagnosis. This retrospective cohort study included 228 patients with newly diagnosed SLE. Clinical characteristics including autoantibody positivity at the time of diagnosis of SLE were reviewed. Flares were defined as a new British Isles Lupus Assessment Group (BILAG) A score or BILAG B score for at least one organ system. Multivariable Cox regression analyses were performed to estimate the risk of flares according to autoantibody positivity. Anti-dsDNA, anti-Sm, anti-U1RNP, anti-Ro, and anti-La antibodies (Abs) were positive in 50.0%, 30.7%, 42.5%, 54.8%, and 22.4% of the patients, respectively. The incidence rate of flares was 28.2/100 person-years. Multivariable Cox regression analysis, adjusted for potential confounders, revealed that anti-dsDNA Ab positivity (adjusted hazard ratio [HR]: 1.46, p = 0.037) and anti-Sm Ab positivity (adjusted HR: 1.81, p = 0.004) at the time of diagnosis of SLE were associated with higher risk of flares. To better delineate the flare risk, patients were categorized as double-negative, single-positive, double-positive for anti-dsDNA and anti-Sm Abs. Compared with double-negativity, double-positivity (adjusted HR: 3.34, p < 0.001) was associated with higher risk of flares, while anti-dsDNA Ab single-positivity (adjusted HR: 1.11, p = 0.620) or anti-Sm Ab single-positivity (adjusted HR: 1.32, p = 0.270) was not associated with higher risk of flares. Patients who are double-positive for anti-dsDNA and anti-Sm Abs at the time of the diagnosis of SLE are at higher risk of flares and may benefit from stringent monitoring and early preventive treatment. © 2023, The Author(s).ope
IL-4 drastically decreases deuterosomal and multiciliated cells via alteration in progenitor cell differentiation
BackgroundAllergic inflammation affects the epithelial cell populations resulting in goblet cell hyperplasia and decreased ciliated cells. Recent advances in single-cell RNA sequencing (scRNAseq) have enabled the identification of new cell subtypes and genomic features of single cells. In this study, we aimed to investigate the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single-cell level. MethodsWe performed scRNAseq in cultured primary human nasal epithelial (HNE) cells and in vivo nasal epithelium. The transcriptomic features and epithelial cell subtypes were determined under IL-4 stimulation, and cell-specific marker genes and proteins were identified. ResultsWe confirmed that cultured HNE cells were similar to in vivo epithelial cells through scRNAseq. Cell-specific marker genes were utilized to cluster the cell subtypes, and FOXJ1(+)-ciliated cells were sub-classified into multiciliated and deuterosomal cells. PLK4 and CDC20B were specific for deuterosomal cells, and SNTN, CPASL, and GSTA2 were specific for multiciliated cells. IL-4 altered the proportions of cell subtypes, resulting in a decrease in multiciliated cells and loss of deuterosomal cells. The trajectory analysis revealed deuterosomal cells as precursor cells of multiciliated cells and deuterosomal cells function as a bridge between club and multiciliated cells. A decrease in deuterosomal cell marker genes was observed in nasal tissue samples with type 2 inflammation. ConclusionThe effects of IL-4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. This study also newly suggests cell-specific markers that might be pivotal for investigating respiratory inflammatory diseases.restrictio