Effects of oridonin on sperm function and the PI3K/PDK1/AKT signaling pathway: Implications for reproductive toxicity.

Oridonin, a natural terpenoid isolated from the leaves of Isodon rubescens (Hemsley) H.Hara, is widely used in oriental medicine for its anticancer properties across various cancer types. Despite its prevalent use, the toxic effects of oridonin on male reproduction, particularly its impact on sperm functions and the mechanisms involved, are not well understood. This study aimed to explore the effects and underlying mechanisms of oridonin on sperm functions. We initially treated Duroc boar spermatozoa with varying concentrations of oridonin (0, 5, 50, 75, 100, and 150 µM) and incubated them to induce capacitation. We then assessed cell viability and several sperm functions, including sperm motility and motion kinematics, capacitation status, and ATP levels. We also analyzed the expression levels of proteins associated with the phosphatidylinositol 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/protein kinase B (AKT) signaling pathway and phosphotyrosine proteins. Our results indicate that oridonin adversely affects most sperm functions in a dose-dependent manner. We observed significant decreases in AKT, p-AKT (Thr308), phosphatase and tensin homolog (PTEN), p-PDK1, and p-PI3K levels following oridonin treatment, alongside an abnormal increase in phosphotyrosine proteins. These findings suggest that oridonin may disrupt normal levels of tyrosine-phosphorylated proteins by inhibiting the PI3K/PDK1/AKT signaling pathway, which is crucial for cell proliferation, metabolism, and apoptosis, thus potentially harming sperm functions. Consequently, we recommend considering the reproductive toxicity of oridonin when using it as a therapeutic agent.

Microbial nitrogen bubble formation in porous media.

Microbially induced nitrogen (N2) gas bubbles can desaturate subsurface areas and thus have been considered as an alternative ground improvement technique for mitigating soil liquefaction potential caused by earthquakes. However, the detailed mechanisms of subsurface N2 bubbles are not well understood and remain a subject of ongoing research. In this study, a transparent microfluidic device was utilized to mimic biological N2 gas bubble formation by nitrate-reducing bacteria and to visually characterize the entire process. During N2 gas formation, a limited number of bubble nucleation sites were identified, which gradually expanded upward through the preferential pore channels. N2 gas bubbles tended to create interconnected gas pockets rather than existing as evenly distributed small gas cavities. The degree of water saturation gradually reduced over a week as the bubbles were produced. The gas ganglia repeatedly grew until they reached the top boundary, which triggered a drastic expulsion of bubbles by ebullition. Despite fluctuations in saturation level, the residual saturation was maintained at around 73 %. Comparative experimental case studies of CO2 gas bubble formation were conducted to identify contrasting gas formation mechanisms. CO2 gas bubbles were generated via the abiotic decompression of a supersaturated CO2 solution under two distinct rates of pressure reduction. Rapid CO2 bubble formation led to uniform nucleation and 41 % residual saturation, while slower formation yielded 35 % due to stable liquid displacement by the gas front. This study highlights the potential of the microfluidic device as an experimental tool for visualizing subsurface gas formation mechanisms. The insights gained could further enhance and optimize geotechnical applications involving gas formation in highly saturated soils.

Changes in femoral anteversion after intramedullary nailing for pediatric femoral shaft fracture: a multicenter study.

BACKGROUND: The rotational change after using a flexible intramedullary (IM) nail for femoral shaft fractures has been a concern for many surgeons. Recently, a statistical shape model (SSM) was developed for the three-dimensional reconstruction of the femur from two-dimensional plain radiographs. In this study, we measured postoperative femoral anteversion (FAV) in patients diagnosed with femoral shaft fractures who were treated with flexible IM nails and investigated age-related changes in FAV using the SSM. METHODS: This study used radiographic data collected from six regional tertiary centers specializing in pediatric trauma in South Korea. Patients diagnosed with femoral shaft fractures between September 2002 and June 2020 and patients aged < 18 years with at least two anteroposterior (AP) and lateral (LAT) femur plain radiographs obtained at least three months apart were included. A linear mixed model (LMM) was used for statistical analysis. RESULTS: Overall, 72 patients were included in the study. The average patient age was 7.6 years and the average follow-up duration was 6.8 years. The average FAV of immediate postoperative images was 27.5 ± 11.5°. Out of 72 patients, 52 patients (72.2%) showed immediate postoperative FAV greater than 20°. The average FAV in patients with initial FAV > 20° was 32.74°, and the LMM showed that FAV decreased by 2.5° (p = 0.0001) with each 1-year increase from the time of initial trauma. CONCLUSIONS: This study explored changes in FAV after femoral shaft fracture using a newly developed technology that allows 3D reconstruction from uncalibrated 2D images. There was a pattern of change on the rotation of the femur after initial fixation, with a 2.5° decrease of FAV per year.

C1 Facetectomy and Ventral Fixation of Occipitoatlantoaxial Complex for Concurrent Congenital Atlanto-Occipital Dislocation and Atlantoaxial Instability in a Toy Poodle.

An 8-month-old, 3.4 kg, castrated male Toy Poodle was referred for progressive tetraparesis and respiratory disorder without a history of trauma. Repeated computed tomography (CT) and magnetic resonance imaging (MRI) with different positions of the neck revealed concurrent atlanto-occipital dislocation (AOD) and atlantoaxial instability (AAI) with spinal cord compression. This case was unique due to its congenital nature and the absence of trauma. The surgical treatment involved precise removal of the C1 vertebra's ventral articular facet, which was compressing on the spinal cord, attributed to its fixed and malaligned position within the atlantooccipital joint. Following facetectomy, the stabilization of the occipital bone to the C2 vertebra was achieved by screws, wire, and polymethyl methacrylate. Two days after surgery, the dog recovered ambulation and showed gradual improvement in gait, despite mild residual ataxia. Postoperative CT and radiographs showed successful decompression of the spinal cord. The screw loosening was confirmed at 114 days, which was managed successfully by extracting the affected screws. Through the 21-month monitoring period, the dog showed a normal gait with a wide-based stance of the pelvic limbs when standing and experienced no pain. This case represents the first report of concurrent congenital AOD and AAI treated with a ventral surgical approach, contributing new insights to the understanding and management of such complex cranio-cervical junction disorders in veterinary neurosurgery.

Automated segmentation of MRI white matter hyperintensities in 8,421 patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: To date, only a few small studies have attempted deep learning-based automatic segmentation of white matter hyperintensity (WMH) lesions in patients with cerebral infarction, which is complicated because stroke-related lesions can obscure WMH borders. We developed and validated deep learning algorithms to segment WMH lesions accurately in patients with cerebral infarction, using multisite datasets involving 8,421 patients with acute ischemic stroke. MATERIALS AND METHODS: We included 8,421 stroke patients from 9 centers in Korea. 2D UNet and SE-Unet models were trained using 2,408 FLAIR MRI from 3 hospitals and validated using 6,013 FLAIR MRIs from 6 hospitals. WMH segmentation performance was assessed by calculating DSC, correlation coefficient, and concordance correlation coefficient compared to a human-segmented gold standard. In addition, we obtained an uncertainty index that represents overall ambiguity in the voxel classification for WMH segmentation in each patient based on the Kullback-Leibler divergence. RESULTS: In the training dataset, the mean age was 67.4±13.0 years and 60.4% were men. The mean (95% CI) DSCs for Unet in internal testing and external validation were respectively 0.659 (0.649-0.669) and 0.710 (0.707-0.714), which were slightly lower than the reliability between humans (DSC=0.744; 95% CI=0.738-0.751; P=.031). Compared with the Unet, the SE-Unet demonstrated better performance, achieving a mean DSC of 0.675 (0.666-0.685; P<.001) in the internal testing and 0.722 (0.719-0.726; P<.001) in the external validation; moreover, it achieved high DSC values (ranging from 0.672 to 0.744) across multiple validation datasets. We observed a significant correlation between WMH volumes that were segmented automatically and manually for the Unet (r=0.917, P<.0001) and even stronger for the SE-Unet (r=0.933, P<.0001). The SE-Unet also attained a high concordance correlation coefficient (ranging from 0.841 to 0.956) in external test datasets. In addition, the uncertainty indices in the majority of patients (86%) in the external datasets were below 0.35, with an average DSC of 0.744 in these patients. CONCLUSIONS: We developed and validated deep learning algorithms to segment WMH in patients with acute cerebral infarction using the largest-ever MRI datasets. In addition, we showed that the uncertainty index can be used to identify cases where automatic WMH segmentation is less accurate and requires human review. ABBREVIATIONS: WMH = white matter hyperintensity; CNN = convolutional neural networks; SE = squeeze-and-excitation; KL = Kullback-Leibler; ReLU = rectified linear unit; LKW = last known well; mRS = modified Rankin Scale; NIHSS = National Institute of Health Stroke Scale; LAA = large artery atherosclerosis; SVO = small vessel occlusion; CE = cardioembolism.

Deep Learning-Based Automatic Classification of Ischemic Stroke Subtype Using Diffusion-Weighted Images.

BACKGROUND AND PURPOSE: Accurate classification of ischemic stroke subtype is important for effective secondary prevention of stroke. We used diffusion-weighted image (DWI) and atrial fibrillation (AF) data to train a deep learning algorithm to classify stroke subtype. METHODS: Model development was done in 2,988 patients with ischemic stroke from three centers by using U-net for infarct segmentation and EfficientNetV2 for subtype classification. Experienced neurologists (n=5) determined subtypes for external test datasets, while establishing a consensus for clinical trial datasets. Automatically segmented infarcts were fed into the model (DWI-only algorithm). Subsequently, another model was trained, with AF included as a categorical variable (DWI+AF algorithm). These models were tested: (1) internally against the opinion of the labeling experts, (2) against fresh external DWI data, and (3) against clinical trial dataset. RESULTS: In the training-and-validation datasets, the mean (±standard deviation) age was 68.0±12.5 (61.1% male). In internal testing, compared with the experts, the DWI-only and the DWI+AF algorithms respectively achieved moderate (65.3%) and near-strong (79.1%) agreement. In external testing, both algorithms again showed good agreements (59.3%-60.7% and 73.7%-74.0%, respectively). In the clinical trial dataset, compared with the expert consensus, percentage agreements and Cohen's kappa were respectively 58.1% and 0.34 for the DWI-only vs. 72.9% and 0.57 for the DWI+AF algorithms. The corresponding values between experts were comparable (76.0% and 0.61) to the DWI+AF algorithm. CONCLUSION: Our model trained on a large dataset of DWI (both with or without AF information) was able to classify ischemic stroke subtypes comparable to a consensus of stroke experts.

Reconstruction of Bilateral Chronic Triceps Brachii Tendon Disruption Using a Suture-Mediated Anatomic Footprint Repair in a Dog.

A 2-year-old, intact female Pomeranian presented with bilateral forelimb lameness, characterized by the olecranon making contact with the ground. The patient experienced two separate incidents of falling, occurring four and three weeks before admission, respectively. Following each episode, non-weight-bearing lameness was initially observed in the left forelimb, followed by the development of crouch gait. Based on the physical examination, radiographic, and ultrasonographic findings, bilateral triceps brachii tendon disruption was diagnosed. Intraoperatively, excessive granulation tissue at the distal end of the tendon was excised. The footprint region of each triceps brachii tendon was decorticated with a high-speed burr until bleeding was observed. The triceps brachii tendon was reattached to completely cover its footprint on the olecranon using the Krackow suture technique. This method involves anchoring the suture through bone tunnels in the ulna. Trans-articular external skeletal fixation was applied to both forelimbs to immobile and stabilize the elbow joints for nine weeks. Subsequently, the dog gradually increased its walking activities while on a leash over a six-week period. At the three-year follow-up, the patient exhibited improved forelimb function and maintained a normal gait without signs of lameness. Suture-mediated anatomic footprint repair proved useful in this single case and may be an effective surgical alternative for the management of chronic triceps brachii tendon disruption in dogs.

Enhancing the Evaluation System of Training Hospitals for Neurosurgical Residency Training and Education in South Korea : Striving for Balanced Participation and Differentiation.

The Korean Neurosurgical Society, with its 62 years of history, has witnessed substantial growth in the field of neurosurgery, producing over 3,400 neurosurgeons, establishing 12 divisions and 9 regional branches, and advancing in clinical management, diagnostic methods and academic research. Despite these developments, the regulations governing neurosurgical training and evaluation methods for training hospitals have remained largely unchanged, necessitating comprehensive revisions in response to evolving medical environments. To provide balanced participation opportunities for neurosurgery residents, the Korean Neurosurgical Society formed the Training Status Investigation Standard Change Task Force (TF Team) under the Training Education Committee. This paper presents the TF Team's findings and proposals for revising training status investigation standards and evaluation criteria. Through the processes including a lot of team meetings, workshops, education programs, official communications with 12 division societies, benchmarking from other societies and analysis of encrypted data from the past 5 years for neurosurgical training hospitals, the TF Team created a revised training status investigation proposal, supplemented main surgery criteria. And we applied this revised proposal to the training status investigation data collected from training hospitals in 2022 for simulation. We reduced the score for main surgeries to 10 points, introduced core competency surgery standards, allocating 5 points each for brain core competency surgery and spine and peripheral core competency surgery, for a total of 10 points. We also adjusted the major surgery score to 13 points, expanding the total surgery index score to 33 points. We introduced additional definitions for main surgeries in the areas of spine, pediatrics, and functional surgery. The equipment score was reduced from 17 points to 9 points. We specified minimum requirements for resident allocation eligibility, and if a hospital meets all of these criteria, they become eligible to apply for resident allocation. We introduced a new bonus point system for hospitals performing mechanical thrombectomy or stenting and peripheral nerve. The proposed revisions aim to improve the training and education of neurosurgical residents and overall neurosurgical care in Korea by creating a balanced and differentiated evaluation system for training hospitals. Further monitoring, communication, and adjustments are crucial for successful implementation.

Molecular genomic and epigenomic characteristics related to aspirin and clopidogrel resistance.

BACKGROUND: Mediators, genomic and epigenomic characteristics involving in metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (ALOX) and hepatic activation of clopidogrel have been individually suggested as factors associated with resistance against aspirin and clopidogrel. The present multi-center prospective cohort study evaluated whether the mediators, genomic and epigenomic characteristics participating in arachidonic acid metabolism and clopidogrel activation could be factors that improve the prediction of the aspirin and clopidogrel resistance in addition to cardiovascular risks. METHODS: We enrolled 988 patients with transient ischemic attack and ischemic stroke who were evaluated for a recurrence of ischemic stroke to confirm clinical resistance, and measured aspirin (ARU) and P2Y12 reaction units (PRU) using VerifyNow to assess laboratory resistance 12 weeks after aspirin and clopidogrel administration. We investigated whether mediators, genotypes, and promoter methylation of genes involved in COX and ALOX metabolisms and clopidogrel activation could synergistically improve the prediction of ischemic stroke recurrence and the ARU and PRU levels by integrating to the established cardiovascular risk factors. RESULTS: The logistic model to predict the recurrence used thromboxane A synthase 1 (TXAS1, rs41708) A/A genotype and ALOX12 promoter methylation as independent variables, and, improved sensitivity of recurrence prediction from 3.4% before to 13.8% after adding the mediators, genomic and epigenomic variables to the cardiovascular risks. The linear model we used to predict the ARU level included leukotriene B4, COX2 (rs20417) C/G and thromboxane A2 receptor (rs1131882) A/A genotypes with the addition of COX1 and ALOX15 promoter methylations as variables. The linear PRU prediction model included G/A and prostaglandin I receptor (rs4987262) G/A genotypes, COX2 and TXAS1 promoter methylation, as well as cytochrome P450 2C19*2 (rs4244285) A/A, G/A, and *3 (rs4986893) A/A genotypes as variables. The linear models for predicting ARU (r = 0.291, R2 = 0.033, p < 0.01) and PRU (r = 0.503, R2 = 0.210, p < 0.001) levels had improved prediction performance after adding the genomic and epigenomic variables to the cardiovascular risks. CONCLUSIONS: This study demonstrates that different mediators, genomic and epigenomic characteristics of arachidonic acid metabolism and clopidogrel activation synergistically improved the prediction of the aspirin and clopidogrel resistance together with the cardiovascular risk factors. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03823274.

Facial Trauma Affects the Radiological Diagnosis of Nasal Bone Fractures.

OBJECTIVES: Timely and accurate diagnosis of nasal bone fractures (NBFs) is crucial for preserving the cosmetic and functional aspects of the nose. This study aims to identify factors influencing radiographic and computed tomography (CT) diagnosis of NBF in patients with nasal trauma. METHODS: Two hundred six patients with acute nasal trauma underwent both conventional radiography and facial bone CT. An experienced otorhinolaryngologist independently interpreted images. Results were categorized into "Concordance" or "Discrepancy" groups, with demographic and clinical data compared. RESULTS: The study classified 167 patients into "Concordance" and 39 into "Discrepancy" groups based on radiography and CT interpretations. The "discrepancy group" showed higher rates of previous nasal bone fractures (P=0.044), rhinoplasty history (P=0.044), and concomitant facial bone fractures (P=0.001). Adjusted odds ratios revealed significant associations between discrepancies and a history of nasal bone fracture (OR=5.197, 95% CI 1.165-23.171), rhinoplasty (OR=6.114, 95% CI 1.393-26.847), and concomitant facial bone fractures (OR=3.765, 95% CI 1.663-8.523). CONCLUSION: This study highlights the impact of facial trauma, including rhinoplasty, on the radiological diagnosis of NBF. Consequently, in the presence of signs of concurrent facial trauma, previous nasal trauma, or rhinoplasty history, a prompt CT scan and comprehensive evaluation are recommended for accurate diagnosis and timely treatment, ultimately improving the patient's prognosis.

SNPs in microRNA seed region and impact of miR-375 in concurrent regulation of multiple lipid accumulation-related genes.

Bovine intramuscular fat (IMF), commonly referred to as marbling, is regulated by lipid metabolism, which includes adipogenesis, lipogenesis, glycerolipid synthesis, and lipolysis. In recent years, breeding researchers have identified single nucleotide polymorphisms (SNPs) as useful marker-assisted selection tools for improving marbling scores in national breeding programs. These included causal SNPs that induce phenotypic variation. MicroRNAs (miRNAs) are small highly conserved non-coding RNA molecules that bind to multiple non-coding regions. They are involved in post-transcriptional regulation. Multiple miRNAs may regulate a given target. Previously, three SNPs in the GPAM 3' UTR and four miRNAs were identified through in silico assays. The aim of this study is to verify the binding ability of the four miRNAs to the SNPs within the 3'UTR of GPAM, and to identify the regulatory function of miR-375 in the expression of genes related to lipid metabolism in mammalian adipocytes. It was verified that the four miRNAs bind to the GPAM 3'UTR, and identified that the miR-375 sequence is highly conserved. Furthermore, it was founded that miR-375 upregulated the GPAM gene, C/EBPα, PPARγ and lipid metabolism-related genes and promoted lipid droplet accumulation in 3T3-L1 cells. In conclusion, these results suggest that miR-375 is a multifunctional regulator of multiple lipid metabolism-related genes and may aid in obesity research as a biomarker.

Trends in Dual Antiplatelet Therapy of Aspirin and Clopidogrel and Outcomes in Ischemic Stroke Patients Noneligible for POINT/CHANCE Trial Treatment.

BACKGROUND: Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT-AC among the patients with nonminor or late-presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. METHODS AND RESULTS: In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT-AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1-7) were analyzed. In 2008, DAPT-AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT-AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend<0.001). From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, myocardial infarction, and all-cause mortality, both among patients treated with DAPT-AC and patients treated with other antiplatelets. CONCLUSIONS: Use of DAPT-AC in stroke patients with stroke ineligible for recent DAPT clinical trials increased markedly and steadily after CHANCE publication in 2013, reaching deployment in nearly 4 of every 5 patients by 2022. The secondary prevention in patients with ischemic stroke seems to be gradually improving, possibly due to the enhancement of risk factor control.

Laparoscopic treatment of paraprostatic cyst in two dogs - complete resection, and partial resection with omentalization: a case report.

Two intact male dogs were evaluated for symptoms, including hematuria, prostatomegaly, anuria, lethargy, and abdominal mass. Presurgical evaluations, including complete physical examinations, blood examinations, abdominal radiography with contrast (only in Case 2), ultrasonography, and computed tomography and magnetic resonance imaging (only in Case 1), were performed. A paraprostatic cyst was diagnosed initially, and laparoscopic exploration and surgery were performed. Complete resection was performed in case 1, whereas partial resection with omentalization was performed in case 2. Histopathological examination of the tissue samples confirmed the presence of paraprostatic pseudocysts in both cases, with no evidence of an epithelial lining. These two cases represent the first documented instances of laparoscopic treatment for extraparenchymal prostatic cysts. The laparoscopic treatment proved feasible even in the case of a giant cyst causing anuria (Case 2). Paraprostatic cysts should be considered a potential differential diagnosis for abnormal urination accompanied by an abdominal mass, and long-term postoperative follow-up is necessary.

Surgical Correction of a Sinus Venosus Atrial Septal Defect with Partial Anomalous Pulmonary Venous Connections Using Cardiac Computed Tomography Imaging and a 3D-Printed Model.

Sinus venosus atrial septal defects (SVASDs), concurrent with partial anomalous pulmonary venous connections (PAPVCs), are a rare congenital heart disease in dogs. Surgical correction is essential when clinical signs or significant hemodynamic changes are present. We aimed to report on the successful surgical correction of an SVASD with PAPVCs, using a computed tomography (CT)-based customized 3D cardiac model. A 10-month-old male poodle was referred for corrective surgery for an ASD. Echocardiography confirmed a hemodynamically significant left-to-right shunting flow through an interatrial septal defect and severe right-sided heart volume overload. For a comprehensive diagnosis, a CT scan was performed, which confirmed an SVASD with PAPVCs. A customized 3D cardiac model was used for preoperative decision-making and surgical rehearsal. The defect was repaired using an autologous pericardial patch under a cardiopulmonary bypass (CPB). Temporary pacing was applied for sinus bradycardia and third-degree atrioventricular block. The patient recovered from the anesthesia without further complications. The pacemaker was removed during hospitalization and the patient was discharged without complications 2 weeks post-surgery. At the three-month follow-up, there was no shunting flow in the interatrial septum and the right-sided volume overload had been resolved. The cardiac medications were discontinued, and there were no complications. This report indicates the validity of surgical correction under CPB for an SVASD with PAPVCs, and the advantages of utilizing a CT-based 3D cardiac model for preoperative planning to increase the surgical success rate.

Randomized controlled trial of digital therapeutics for temporomandibular disorder: A pilot study.

OBJECTIVES: Temporomandibular disorder (TMD) is a common condition that affects the temporomandibular joint (TMJ) and the muscles of the jaw, resulting in pain and dysfunction. TMD is affected by both behavioral and psychological factors. Digital therapeutics (DTx) can exert therapeutic effects by controlling behavioral factors through the delivery of appropriate interventions. Here, we report an open-label randomized control trial to evaluate the efficacy of DTx for TMD. METHODS: We recruited 40 participants diagnosed with TMD. Participants were randomly divided into an intervention group (DTx use, n = 20) and a control group (n = 20). The intervention group received the usual treatment process for TMD in addition to the use of the DTx. The control group received the usual treatments only. Patients in both groups were followed up for 3-4 weeks, and outcome data were collected and analyzed. RESULT: The intervention group showed a significant reduction in pain scores as measured by the numerical rating scale (NRS) (p = 0.016). Additionally, the intervention group showed a statistically significant increase in maximal mouth opening compared to the control group (p = 0.0079). However, there were no significant differences in improvement in the Jaw Functional Limitation Scale, Oral Behavior Checklist, and Patient Health Questionnaire-4 between the two groups (p = 0503, = 0.820, and = 0.943, respectively). CONCLUSION: This RCT reveals DTx potential in TMD, showing pain and mouth opening improvements with conventional treatment. But no significant changes were noted in other outcomes. The findings advocate for more extensive, long-term research to solidify DTx's role in TMD management. CLINICAL SIGNIFICANCE: This research underlines DTx potential to improve pain outcomes in TMD therapy, reinforcing its value as a complementary treatment modality.

Machine learning-based analysis for prediction of surgical necrotizing enterocolitis in very low birth weight infants using perinatal factors: a nationwide cohort study.

Early prediction of surgical necrotizing enterocolitis (sNEC) in preterm infants is important. However, owing to the complexity of the disease, identifying infants with NEC at a high risk for surgical intervention is difficult. We developed a machine learning (ML) algorithm to predict sNEC using perinatal factors obtained from the national cohort registry of very low birth weight (VLBW) infants. Data were collected from the medical records of 16,385 VLBW infants registered in the Korean Neonatal Network (KNN). Infants who underwent surgical intervention were identified with sNEC, and infants who received medical treatment, with medical NEC (mNEC). We used 38 variables, including maternal, prenatal, and postnatal factors that were obtained within 1 week of birth, for training. A total of 1085 patients had NEC (654 with sNEC and 431 with mNEC). VLBW infants showed a higher incidence of sNEC at a lower gestational age (GA) (p < 0.001). Our proposed ensemble model showed an area under the receiver operating characteristic curve of 0.721 for sNEC prediction.    Conclusion: Proposed ensemble model may help predict which infants with NEC are likely to develop sNEC. Through early prediction and prompt intervention, prognosis of sNEC may be improved. What is Known: • Machine learning (ML)-based techniques have been employed in NEC research for prediction, diagnosis, and prognosis, with promising outcomes. • While most studies have utilized abdominal radiographs and clinical manifestations of NEC as data sources, and have demonstrated their usefulness, they may prove weak in terms of early prediction. What is New: • We analyzed the perinatal factors of VLBW infants acquired within 7 days of birth and used ML-based analysis to identify which infants with NEC are vulnerable to clinical deterioration and at high risk for surgical intervention using nationwide cohort data.

Secular Trends in Outcomes and Impact of Novel Oral Anticoagulants in Atrial Fibrillation-Related Acute Ischemic Stroke.

BACKGROUND: Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend. METHODS: We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders. RESULTS: Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07-1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14-2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94-1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome. CONCLUSIONS: Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population.

Adverse Effects of Avobenzone on Boar Sperm Function: Disruption of Protein Kinase A Activity and Tyrosine Phosphorylation.

Avobenzone (AVO), an ultraviolet (UV) filter, is frequently used as an ingredient in personal cosmetics. This UV filter has been found to be easily exposed in swimming pools and beaches, and it has been detected in human urine and blood. Moreover, numerous studies have demonstrated that AVO exhibits endocrine-disrupting properties. Nevertheless, the effects of AVO on male fertility have not yet fully understood. Therefore, this study aimed to assess the effects of AVO on various sperm functions during capacitation. First, boar spermatozoa were treated with various AVO concentrations. After treatment, sperm motility and kinetic characteristics, capacitation status, intracellular adenosine triphosphate (ATP) levels, and sperm viability were evaluated. Moreover, Western blot analysis w.as conducted to evaluate protein kinase A (PKA) activity and tyrosine phosphorylation. As a result, AVO treatment significantly decreased total motility, progressive motility, and several kinetic characteristics at high concentrations (50 and 100 µM). Furthermore, the capacitation status dose-dependently decreased. Conversely, no significant differences in acrosome reaction, cell viability, and intracellular ATP levels were observed. However, the intracellular ATP level tended to decrease. In addition, AVO dose-dependently induced abnormal changes in PKA activity and tyrosine phosphorylation. Although AVO did not directly exert a toxic effect on cell viability, it ultimately negatively affected sperm functions through abnormal alterations in PKA activity and tyrosine phosphorylation. Thus, the potential implications on male fertility must be considered when contemplating the safe utilization of AVO.