Highly efficient and specific regulation of gene expression using enhanced CRISPR-Cas12f system.

The recently developed CRISPR activator (CRISPRa) system uses a CRISPR-Cas effector-based transcriptional activator to effectively control the expression of target genes without causing DNA damage. However, existing CRISPRa systems based on Cas9/Cas12a necessitate improvement in terms of efficacy and accuracy due to limitations associated with the CRISPR-Cas module itself. To overcome these limitations and effectively and accurately regulate gene expression, we developed an efficient CRISPRa system based on the small CRISPR-Cas effector Candidatus Woesearchaeota Cas12f (CWCas12f). By engineering the CRISPR-Cas module, linking activation domains, and using various combinations of linkers and nuclear localization signal sequences, the optimized eCWCas12f-VPR system enabled effective and target-specific regulation of gene expression compared with that using the existing CRISPRa system. The eCWCas12f-VPR system developed in this study has substantial potential for controlling the transcription of endogenous genes in living organisms and serves as a foundation for future gene therapy and biological research.

Metabolic flux optimization of iterative pathways through orthogonal gene expression control: Application to the ß-oxidation reversal.

Balancing relative expression of pathway genes to minimize flux bottlenecks and metabolic burden is one of the key challenges in metabolic engineering. This is especially relevant for iterative pathways, such as reverse ß-oxidation (rBOX) pathway, which require control of flux partition at multiple nodes to achieve efficient synthesis of target products. Here, we develop a plasmid-based inducible system for orthogonal control of gene expression (referred to as the TriO system) and demonstrate its utility in the rBOX pathway. Leveraging effortless construction of TriO vectors in a plug-and-play manner, we simultaneously explored the solution space for enzyme choice and relative expression levels. Remarkably, varying individual expression levels led to substantial change in product specificity ranging from no production to optimal performance of about 90% of the theoretical yield of the desired products. We obtained titers of 6.3 g/L butyrate, 2.2 g/L butanol and 4.0 g/L hexanoate from glycerol in E. coli, which exceed the best titers previously reported using equivalent enzyme combinations. Since a similar system behavior was observed with alternative termination routes and higher-order iterations, we envision our approach to be broadly applicable to other iterative pathways besides the rBOX. Considering that high throughput, automated strain construction using combinatorial promoter and RBS libraries remain out of reach for many researchers, especially in academia, tools like the TriO system could democratize the testing and evaluation of pathway designs by reducing cost, time and infrastructure requirements.

A multicentre, double-blind, placebo-controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add-on therapy in type 2 diabetic patients treated with metformin and dapagliflozin.

AIM: To investigate the efficacy and safety of pioglitazone compared to placebo when added to metformin plus dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, for patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: In a multicentre study, with a randomized, double-blind, placebo-controlled design, 249 Korean patients with T2DM suboptimally managed on metformin and dapagliflozin were assigned to receive either pioglitazone (15 mg daily) or placebo for 24 weeks, followed by a 24-week pioglitazone extension. Primary outcomes included changes in glycated haemoglobin (HbA1c), with secondary outcomes assessing insulin resistance, adiponectin levels, lipid profiles, liver enzymes, body weight and waist circumference. RESULTS: Pioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo (from 7.79% ± 0.76% to 7.69% ± 0.86%, corrected mean difference: -0.42% ± 0.08%; p < 0.01) at 24 weeks. Additional benefits from pioglitazone treatment included enhanced insulin sensitivity, increased adiponectin levels, raised high-density lipoprotein cholesterol levels and reduced liver enzyme levels, resulting in improvement in nonalcoholic fatty liver disease liver fat score. Despite no serious adverse events in either group, pioglitazone therapy was modestly but significantly associated with weight gain and increased waist circumference. CONCLUSIONS: Adjunctive pioglitazone treatment in T2DM inadequately controlled with metformin and dapagliflozin demonstrates considerable glycaemic improvement, metabolic benefits, and a low risk of hypoglycaemia. These advantages must be weighed against the potential for weight gain and increased waist circumference.

Decision regret after prostate biopsy for prostate cancer diagnosis: a Korean multicenter cohort study.

BACKGROUND: Many people struggle with the choice in a series of processes, from prostate cancer (PCa) diagnosis to treatment. We investigated the degree of regret after the prostate biopsy (PBx) and relevant factors in patients recommended for biopsy for suspected PCa. METHODS: From 06/2020 to 05/2022, 198 people who performed PBx at three institutions were enrolled and analyzed through a questionnaire before and after biopsy. Before the biopsy, a questionnaire was conducted to evaluate the sociodemographic information, anxiety scale, and health literacy, and after PBx, another questionnaire was conducted to evaluate the decision regret scale. For patients diagnosed as PCa after biopsy, a questionnaire was conducted when additional tests were performed at PCa staging work-up. RESULTS: 190 patients answered the questionnaire before and after PBx. The mean age was 66.2 ± 7.8 years. Overall, 5.5% of men regretted biopsy, but there was no significant difference between groups according to the PCa presence. Multivariate analysis, to identify predictors for regret, revealed that the case when physicians did not properly explain what the prostate-specific antigen (PSA) test was like and what PSA elevation means (OR 20.57, [95% CI 2.45-172.70], p = 0.005), low media literacy (OR 10.01, [95% CI 1.09-92.29], p = 0.042), and when nobody to rely on (OR 8.49, [95% CI 1.66-43.34], p = 0.010) were significantly related. CONCLUSIONS: Overall regret related to PBx was low. Decision regret was more significantly related to media literacy rather than to educational level. For patients with relatively low media literacy and fewer people to rely on in case of serious diseases, more careful attention and counseling on PBx, including a well-informed explanation on PSA test, is helpful.

Effect of Corticosteroid Use on the Occurrence and Progression of Osteonecrosis of the Femoral Head: A Nationwide Nested Case-Control Study.

BACKGROUND: Although it is very well known that corticosteroids cause osteonecrosis of the femoral head (ONFH), it is unclear as to which patients develop ONFH. Additionally, there are no studies on the association between corticosteroid use and femoral head collapse in ONFH patients. We aimed to investigate the association between corticosteroid use and the risk of ONFH among the general population and what factors affect ONFH occurrence. Additionally, we aimed to demonstrate which factors affect femoral head collapse and total hip arthroplasty (THA) after ONFH occurrence. METHODS: A nationwide, nested case-control study was conducted with data from the National Health Insurance Service Physical Health Examination Cohort (2002 to 2019) in the Republic of Korea. We defined ONFH (N = 3,500) using diagnosis and treatment codes. Patients who had ONFH were matched 1:5 to form a control group based on the variables of birth year, sex, and follow-up duration. Additionally, in patients who have ONFH, we looked for risk factors for progression to THA. RESULTS: Compared with the control group, ONFH patients had a low household income and had more diabetes, hypertension, dyslipidemia, and heavy alcohol use (drinking more than 3 to 7 drinks per week). Systemic corticosteroid use (≥1,800 mg) was significantly associated with an increased risk of ONFH incidence. However, lipid profiles, corticosteroid prescription, and cumulative doses of corticosteroid did not affect the progression to THA. CONCLUSIONS: The ONFH risk increased rapidly when cumulative prednisolone use was ≥1,800 mg. However, oral or high-dose intravenous corticosteroid use and cumulative dose did not affect the prognosis of ONFH. Since the occurrence and prognosis of ONFH are complex and multifactorial processes, further study is needed.

Vagus Nerves Stimulation: Clinical Implication and Practical Issue as a Neuropsychiatric Treatment.

Vagus nerve stimulation (VNS) has been approved as an adjunctive treatment for epilepsy and depression. As the progress of VNS treatment for these neuropsychiatric disorders continues, its applications have expanded to a wide range of conditions, including inflammatory diseases to cognitive dysfunctions. The branches of the vagal nerves directly or indirectly innervate the anatomical structures implicated in these neuropsychiatric conditions, which has led to promising results regarding the effectiveness of VNS. Previous studies investigating the effectiveness of VNS have mostly utilized invasive forms of stimulation. However, current preclinical and clinical research indicates that non-invasive forms of VNS, such as transcutaneous vagus nerve stimulation, hold the promise for treating various neuropsychiatric conditions. This review aims to delve into relevant clinical studies of VNS in various illness states, different methods of VNS, and the potential mechanisms underlying the therapeutic effects in these neuropsychiatric conditions.

Transcranial Electrical Stimulation: Clinical Implication and Practice for Treatment of Psychiatric Illness.

Brain electrical stimulation, particularly non-invasive brain stimulation (NIBS) techniques such as transcranial electrical stimulation (tES), have emerged as a promising treatment for various psychiatric disorders, including depression, anxiety, and post-traumatic stress disorder. tES techniques, such as transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS), are cost-effective and safe interventions that are designed to affect neuronal circuits in the brain using various modalities. Although tES has shown effectiveness in the treatment of psychiatric disorders, there is a lack of comprehensive papers that consider its clinical implications. Therefore, this review aims to evaluate the clinical implications of tES and provide practical guidance for the treatment of psychiatric illnesses. Moreover, this review provides an overview of tES techniques and their mechanisms of action and summarizes recent clinical studies that have examined the use of tES for psychiatric disorders.

Accuracy and Safety of the 15-Day CareSens Air Continuous Glucose Monitoring System.

Background: We evaluated the accuracy and safety of the CareSens Air, a novel real-time continuous glucose monitoring system (CGMS), during 15 days of use in adults with diabetes. Methods: Adults with either type 1 diabetes or type 2 diabetes requiring intensive insulin therapy participated at four sites in South Korea. All participants wore the sensor for 15 days. Participants were scheduled for four 8-h clinic sessions on Day 1, 5 ± 1, 10 ± 1, and 15. Accuracy was evaluated based on the proportion of continuous glucose monitoring (CGM) values within 15% of YSI values ≥100 mg/dL or within 15 mg/dL of YSI values <100 mg/dL (%15/15), along with the %20/20, %30/30, and %40/40 agreement rates. The mean absolute relative difference (MARD) between the CGM and YSI values was calculated. Results: Data from 83 participants (83 sensors, 10,029 CGM-YSI matched pairs) were analyzed. The overall MARD was 10.42%, and the overall %15/15, %20/20, %30/30, and %40/40 accuracy were 78.55%, 89.04%, 96.47%, and 98.87%, respectively. The consensus error grid analysis showed that 99.92% of CGM values fell into Zone A or B (Zone A: 89.83%, Zone B: 10.09%). The %20/20 accuracy of CGMS was 88.11% on Day 1, 90.11% on Day 3-5, 92.09% on Day 8-10, and 85.63% on Day 15. No serious adverse events were reported. Conclusions: The CareSens Air demonstrated accurate performance across the wide glycemic range and was well tolerated during the 15-day sensor use period.

Effects of Oxidized Metal Powders on Pore Defects in Powder-Fed Direct Energy Deposition.

Laser-based additive manufacturing processes, particularly direct energy deposition (DED), have gained prominence for fabricating complex, functionally graded, or customized parts. DED employs a high-powered heat source to melt metallic powder or wire, enabling precise control of grain structures and the production of high-strength objects. However, common defects, such as a lack of fusion and pores between layers or beads, can compromise the mechanical properties of the printed components. This study focuses on investigating the recurrent causes of pore defects in the powder-fed DED process, with a specific emphasis on the influence of oxidized metal powders. This research explores the impact of intentionally oxidizing metal powders of hot work tool steel H13 by exposing them to regulated humidity and temperature conditions. Scanning electron microscopy images and energy-dispersive X-ray spectroscopy results demonstrate the clumping of powders and the deposition of iron oxides in the oxidized powders at elevated temperatures (70 °C for 72 h). Multi-layered depositions of the oxidized H13 powders on STD61 substrate do not show significant differences in cross sections among specimens, suggesting that oxidation does not visibly form large pores. However, fine pores, detected through CT scanning, are observed in depositions of oxidized powders at higher temperatures. These fine pores, typically less than 250 µm in diameter, are irregularly distributed throughout the deposition, indicating a potential degradation in mechanical properties. The findings highlight the need for careful consideration of oxidation effects in optimizing process parameters for enhanced additive manufacturing quality.

Diabetes duration, cholesterol levels, and risk of cardiovascular diseases in individuals with type 2 diabetes.

OBJECTIVE: To investigate the association of diabetes duration with cardiovascular disease (CVD) risk and to examine the relationship between lipid levels and CVD risk over the duration. METHODS: Using the Korean National Health Insurance Service Cohort database, we identified 2,359,243 subjects with type 2 DM aged ≥20 years in 2015-2016. Baseline lipid levels and diabetes duration were evaluated, and followed up until December 2020 (mean follow-up, 3.9 years). Subjects were categorized according to diabetes duration (new-onset, <5 years, 5-9 years, or ≥10 years). We analyzed the new-onset diabetes group with low-density lipoprotein cholesterol (LDL-C), <70 mg/dL, as the reference group. The hazard ratios (HRs) and 95% confidence intervals (CIs) of myocardial infarction (MI), and ischemic stroke (IS) were estimated using a Cox proportional hazards model adjusted for potential confounders. RESULTS: During follow-up, 45,883 cases of MI and 53,538 cases of IS were identified. The risk of MI or IS began to increase at LDL-C ≥160 mg/dL in the new-onset diabetes group, and at LDL-C ≥130 mg/dL in the diabetes duration <5 years group. Among subjects with a diabetes duration of 5-9 years, LDL-C 100-129 mg/dL, LDL-C 130-159 mg/dL, and ≥160 mg/dL were significantly associated with the risk of MI, with HRs (95% CI) of 1.13 (1.04-1.22), 1.28 (1.17-1.39), and 1.58 (1.42-1.76), respectively. The risk of MI in the diabetes duration ≥10 years group was increased by 16%, even in the LDL-C 70-99 mg/dL population (HR [95% CI] 1.16 [1.08-1.25]). CONCLUSIONS: This population-based longitudinal study revealed that the LDL-C cutoff level for increasing the risk of cardiovascular disease varied with diabetes duration, and that the target LDL-C level should depend on the duration.

Physical Inactivity and Sedentariness in Older Hearing Loss patients: Restoration With Hearing Aids.

OBJECTIVES: Hearing loss causes numerous functional deficits. However, few studies have been conducted to assess the association between hearing loss and physical inactivity. This study aimed to evaluate the physical activity and sedentary behavior of hearing loss patients and their relation with the use of hearing aids. MATERIALS AND METHODS: We extracted participants over 60 years of age with information on hearing status and physical activities from the eighth Korea National Health and Nutritional Examination Survey conducted from 2019 to 2020. We classified them into four groups: a normal hearing group (≤25 dB), a mild hearing loss group (>25 dB and ≤40 dB), a moderate hearing loss group (>40 dB and ≤50 dB), and a non-serviceable hearing group (>50 dB). Additionally, we extracted hearing aid users with hearing levels exceeding 50 dB. RESULTS: After adjusting other factors, the non-serviceable hearing group walked less frequently than the moderate (p = 0.004) and mild hearing loss group (p < 0.001) and walked less and sat more than the normal hearing group (walking frequency: p < 0.001; walking time: p = 0.020; and sitting time: p = 0.034). Also, the hearing aid users walked more frequently (p = 0.003) and for longer (p = 0.045) than the non-serviceable hearing group. CONCLUSION: Hearing loss is associated with reduced walking and a sedentary lifestyle. The use of hearing aids is associated with improved physical activity. Appropriate interventions, including hearing aids, should be provided to hearing loss patients. LEVEL OF EVIDENCE: 3 (individual cross-sectional study) Laryngoscope, 2024.

Assessing the accuracy and reliability of application-based audiometry for hearing evaluation.

Pure-tone audiometry (PTA) is the gold standard for assessing hearing loss. However, traditional PTA tests require specialized equipment, trained personnel, and a soundproof environment. Recently, smartphone-based PTA tests have been developed as an alternative method for hearing assessment. The aim of this study was to validate the accuracy and reliability of a smartphone application-based audiometry test. This study was conducted to assess the performance of application-based audiometry from November 2021 to January 2022. Pure-tone thresholds were measured using a smartphone application-based PTA test and compared with results obtained using a traditional audiometer in a sound-treated booth. The smartphone application used in this study was the "Care4Ear (Care4ear, version 1.0.6, MIJ Co., Ltd.)". Hearing thresholds less than 35 dB HL were classified as group A, 35-64 dB HL as group B, and 65 dB HL or greater as group C for the classification of hearing levels. We evaluated the accuracy of smartphone audiometry for each group and compared the results of frequency-specific hearing tests. Additionally, we examined the results of smartphone audiometry in individuals (n = 27) with asymmetric hearing loss. Seventy subjects completed both conventional audiometry and smartphone application-based hearing tests. Among the ears assessed, 55.7% were classified as group A, while 25.7% and 18.6% were classified as group B and group C, respectively. The average hearing threshold obtained from conventional pure-tone audiometry was 37.7 ± 25.2 dB HL, whereas the application-based hearing test yielded thresholds of 21.0 ± 23.0 dB HL. A significant correlation (r = 0.69, p < 0.01) was found between the average hearing thresholds obtained from the application-based and conventional pure-tone audiometry tests. The application-based test achieved a 97.4% hit rate for classifying hearing thresholds as class A, but lower rates of 22.2% for class B and 38.5% for class C. Notably, a discrepancy was observed between the hearing threshold measured by the application and the conventional audiometry for the worse ear with asymmetric hearing. The smartphone-based audiometry is a feasible method for hearing evaluation especially in persons with normal hearing. In cases of hearing loss or asymmetric hearing loss, the results of the application-based audiometry may be inaccurate, limiting its diagnostic utility.

A Host Receptor Nanodisc-Based Biosensor Platform for the Detection of a Specific Virus and Its Variants.

The host receptor is a key element in the initial stage of the virus entry into the host. The use of this host receptor is valuable as a sensing element for selectively and sensitively detecting specific viruses. Also, viruses tend to escape neutralizing antibodies through viral mutation but still utilize the cell entry process using the same host receptors, so it would be a powerful detection tool even for the mutant viruses. The angiotensin-converting enzyme 2 (ACE2) receptor, which is the representative host receptor, performs an essential function in facilitating viral penetration by interacting with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. In this study, we introduce a novel approach, where we fabricated a carbon nanotube field-effect transistor (CNT-FET) sensor and combined it with ACE2 receptor-embedded nanodisc (ND). ACE2 was produced using an E. coli expression system, purified, and integrated into the ND platform. ACE2 NDs showed robust functionality through interactions with a pseudotyped virus (PV) containing the spike protein, enabling sensitive detection of both SARS-CoV-2 and its genetic variations at 102 PFU/mL. The ACE ND-based sensor exhibited excellent selectivity by accurately differentiating SARS-CoV-2 wild-type and variants (Omicron, Delta) from other viruses (ZIKA and MERS-CoV). As a result of comparative analysis, ACE2 ND showed approximately 49% superior long-term functionality up to the second week compared to that of soluble ACE2. These findings highlight the high selectivity and sensitivity of host receptor-based sensors for detecting viral variants and provide a promising tool to prevent the spread of unknown viruses.

Depressive symptoms of people living in areas with high exposure to environmental noise: a multilevel analysis.

Exposure and damage caused by noise have been reported in many countries around the world. However, few nationwide studies explored the association of residential environmental noise with depressive symptoms, this study aims to examine this association. The Korean Community Health Survey at the individual-level and the Korean Environmental Noise Measurement Database at the regional-level were used. A total of 30,630 individuals were eligible for the analysis. Multilevel model framework was applied to account for the clustered structure of the regional-level data in which individual-level data containing demographic characteristics and health information were nested. As a result of the analysis, Individuals living in the highest environmental noise area had a 1.55 times higher likelihood of experiencing depressive symptoms than those living in the lowest environmental noise area (95% CI, 1.04-2.31). After stratified analysis according to depressive symptom severity, individuals residing in areas with the highest environmental noise exposure had significantly higher odds of mild (aOR, 1.46; 95% CI, 1.02-2.07) and moderate symptoms (aOR, 1.70; 95% CI, 1.00-2.91). In conclusion, the higher the residential environmental noise, the higher the possibility of mild-to-moderate depressive symptoms. Our findings suggest the need for continued attention to and management of noise pollution, which has the potential to adversely affect individual's mental health.

Bacterial neuraminidase inhibitory chalcones from flowers of Coreopsis lanceolata, their kinetic characterization and antibiofilm effect.

BACKGROUND: Bacteria within biofilms are thousand times more resistant to antibiotics. Neuraminidase is a crucial enzyme for bacterial adhesion and biofilm formation, it hydrolyzes glycosidic residue of glycoproteins, glycolipids, and oligosaccharides. Coreopsis lanceolata L. flowers may have a significant potential of bacterial neuraminidase (BNA) inhibition because of high natural abundance of chalcones. PURPOSE: The investigation of bacterial biofilm inhibitors has emerged as a novel therapeutic strategy against antibiotic resistance. Therefore, individual chalcones were isolated from C. lanceolata and their capacity to inhibit BNA and formation of Escherichia coli biofilm were evaluated. METHODS: Different chromatographic techniques were used to isolate the compounds (1-12). Enzyme inhibition and detailed kinetic behavior of compounds was determined by estimation of kinetic parameters (Michaelis-Menten constants (Km), maximum velocity (Vmax), dissociation constant for binding with the free enzyme (KI) and enzyme-substate complex (KIS)). Binding affinities (KSV) and binding modes of inhibitors were elucidated by fluorescence quenching and molecular docking, respectively. The natural abundance of chalcones was established through UPLC-Q-TOF/MS. The most potent inhibitor (1) was tested for its ability to inhibit the formation of E. coli biofilm, which was examined by crystal violet assay, scanning electron microscope (SEM) and confocal laser scanning microscope (CLSM). RESULTS: A series of eight chalcones (1-8) and four chalcone glucosides (9-12), inhibited BNA in a dose-dependent manner with IC50 of 8.3 ∼ 77.0 µM. The most potent chalcones were butein (1, IC50 = 8.3 µM) and its glucoside 9 (IC50 = 13.8 µM). The aglycones (1-8) showed non-competitive inhibition, while chalcone glucosides (9-12) displayed a mixed type I (KI < KIS). Inhibitory behaviors were doubly confirmed by KSV and matched with tendency of IC50. The functional group responsible for BNA inhibition were disclosed as 4'-hydroxyl group on B-ring by structure activity relationship (SAR) and molecular docking experiments. Butein (1) suppressed E. coli biofilm formation by > 50 % at 100 µM according to crystal violet assay, which was confirmed by SEM and CLSM imaging. CONCLUSION: The results showed that chalcones (1-8) and chalcone glucosides (9-12), metabolites isolated from the flowers of C. lanceolata, had BNA inhibitory and antibiofilm formation effect on E. coli.

Clinical Implication of Maumgyeol Basic Biotypes-Electroencephalography- and Photoplethysmogram-Based Bwave State Inventory.

OBJECTIVE: The development of individual subtypes based on biomarkers offers a cost-effective and timely avenue to comprehending individual differences pertaining to mental health, independent from individuals' subjective insights. Incorporating 2-channel electroencephalography (EEG) and photoplethysmogram (PPG), we sought to establish a subtype classification system with clinical relevance. METHODS: One hundred healthy participants and 99 patients with psychiatric disorders were recruited. Classification thresholds were determined using the EEG and PPG data from 2,278 individuals without mental disorders, serving to classify subtypes in our sample of 199 participants. Multivariate analysis of variance was applied to examine psychological distinctions among these subtypes. K-means clustering was employed to verify the classification system. RESULTS: The distribution of subtypes differed between healthy participants and those with psychiatric disorders. Cognitive abilities were contingent upon brain subtypes, while mind subtypes exhibited significant differences in symptom severity, overall health, and cognitive stress. K-means clustering revealed that the results of our theory-based classification and data-driven classification are comparable. The synergistic assessment of both brain and mind subtypes was also explored. CONCLUSION: Our subtype classification system offers a concise means to access individuals' mental health. The utilization of EEG and PPG signals for subtype classification offers potential for the future of digital mental healthcare.

Machine learning model based on radiomics features for AO/OTA classification of pelvic fractures on pelvic radiographs.

Depending on the degree of fracture, pelvic fracture can be accompanied by vascular damage, and in severe cases, it may progress to hemorrhagic shock. Pelvic radiography can quickly diagnose pelvic fractures, and the Association for Osteosynthesis Foundation and Orthopedic Trauma Association (AO/OTA) classification system is useful for evaluating pelvic fracture instability. This study aimed to develop a radiomics-based machine-learning algorithm to quickly diagnose fractures on pelvic X-ray and classify their instability. data used were pelvic anteroposterior radiographs of 990 adults over 18 years of age diagnosed with pelvic fractures, and 200 normal subjects. A total of 93 features were extracted based on radiomics:18 first-order, 24 GLCM, 16 GLRLM, 16 GLSZM, 5 NGTDM, and 14 GLDM features. To improve the performance of machine learning, the feature selection methods RFE, SFS, LASSO, and Ridge were used, and the machine learning models used LR, SVM, RF, XGB, MLP, KNN, and LGBM. Performance measurement was evaluated by area under the curve (AUC) by analyzing the receiver operating characteristic curve. The machine learning model was trained based on the selected features using four feature-selection methods. When the RFE feature selection method was used, the average AUC was higher than that of the other methods. Among them, the combination with the machine learning model SVM showed the best performance, with an average AUC of 0.75±0.06. By obtaining a feature-importance graph for the combination of RFE and SVM, it is possible to identify features with high importance. The AO/OTA classification of normal pelvic rings and pelvic fractures on pelvic AP radiographs using a radiomics-based machine learning model showed the highest AUC when using the SVM classification combination. Further research on the radiomic features of each part of the pelvic bone constituting the pelvic ring is needed.

Bioelectronic sensing platform emulating the human endocannabinoid system for assessing and modulating of cannabinoid activity.

Cannabinoids are involved in physiological and neuromodulatory processes through their interactions with the human cannabinoid receptor-based endocannabinoid system. Their association with neurodegenerative diseases and brain reward pathways underscores the importance of evaluating and modulating cannabinoid activity for both understanding physiological mechanisms and developing therapeutic drugs. The use of agonists and antagonists could be strategic approaches for modulation. In this study, we introduce a bioelectronic sensor designed to monitor cannabinoid binding to receptors and assess their agonistic and antagonistic properties. We produced human cannabinoid receptor 1 (hCB1R) via an Escherichia coli expression system and incorporated it into nanodiscs (NDs). These hCB1R-NDs were then immobilized on a single-walled carbon nanotube field-effect transistor (swCNT-FET) to construct a bioelectronic sensing platform. This novel system can sensitively detect the cannabinoid ligand anandamide (AEA) at concentrations as low as 1 fM, demonstrating high selectivity and real-time response. It also successfully identified the hCB1R agonist Δ9-tetrahydrocannabinol and observed that the hCB1R antagonist rimonabant diminished the sensor signal upon AEA binding, indicating the antagonism-based modulation of ligand interaction. Consequently, our bioelectronic sensing platform holds potential for ligand detection and analysis of agonism and antagonism.

Signatures of selection in Angus and Hanwoo beef cattle using imputed whole genome sequence data.

In this study, we detected signatures of selection in Hanwoo and Angus beef cattle using allele frequency and haplotype-based methods based on imputed whole genome sequence variants. Our dataset included 13,202 Angus animals with 10,057,633 imputed SNPs and 10,437 Hanwoo animals with 13,241,550 imputed SNPs. The dataset was subset down to 6,873,624 SNPs in common between the two populations to identify within population (runs of homozygosity, extended haplotype homozygosity) and between population signals of selection (allele fixation index, extended haplotype homozygosity). Assuming these selection signals were complementary to each other, they were combined into a decorrelated composite of multiple signals to identify regions under selection for each of the breeds. 27 genomic regions spanning 25.15 Mb and harboring 360 genes were identified in Angus on chromosomes 1,3, 4, 5, 6, 7, 8, 12, 13, 14, 16, 20, 21 and 28. Similarly, in Hanwoo, 59 genes and 17 genomic regions spanning 5.21 Mb on chromosomes 2, 4, 5, 6, 7, 8, 9, 10, 13, 17, 20 and 24 were identified. Apart from a small region on chromosome 13, there was no major overlap of selection signals between the two breeds reflecting their largely different selection histories, environmental challenges, breeding objectives and breed characteristics. Positional candidate genes identified in selected genomic regions in Angus have been previously associated with growth, immunity, reproductive development, feed efficiency and adaptation to environment while the candidate genes identified in Hanwoo included important genes regulating meat quality, fat deposition, cholesterol metabolism, lipid synthesis, neuronal development, and olfactory reception.