A human brain atlas of χ-separation for normative iron and myelin distributions.

Iron and myelin are primary susceptibility sources in the human brain. These substances are essential for a healthy brain, and their abnormalities are often related to various neurological disorders. Recently, an advanced susceptibility mapping technique, which is referred to as χ-separation (pronounced as "chi"-separation), has been proposed, successfully disentangling paramagnetic iron from diamagnetic myelin. This method provided a new opportunity for generating high-resolution iron and myelin maps of the brain. Utilizing this technique, this study constructs a normative χ-separation atlas from 106 healthy human brains. The resulting atlas provides detailed anatomical structures associated with the distributions of iron and myelin, clearly delineating subcortical nuclei, thalamic nuclei, and white matter fiber bundles. Additionally, susceptibility values in a number of regions of interest are reported along with age-dependent changes. This atlas may have direct applications such as localization of subcortical structures for deep brain stimulation or high-intensity focused ultrasound and also serve as a valuable resource for future research.

Efficacy of personalized repetitive transcranial magnetic stimulation based on functional reserve to enhance ambulatory function in patients with Parkinson's disease: study protocol for a randomized controlled trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is one of the non-invasive brain stimulations that modulate cortical excitability through magnetic pulses. However, the effects of rTMS on Parkinson's disease (PD) have yielded mixed results, influenced by factors including various rTMS stimulation parameters as well as the clinical characteristics of patients with PD. There is no clear evidence regarding which patients should be applied with which parameters of rTMS. The study aims to investigate the efficacy and safety of personalized rTMS in patients with PD, focusing on individual functional reserves to improve ambulatory function. METHODS: This is a prospective, exploratory, multi-center, single-blind, parallel-group, randomized controlled trial. Sixty patients with PD will be recruited for this study. This study comprises two sub-studies, each structured as a two-arm trial. Participants are classified into sub-studies based on their functional reserves for ambulatory function, into either the motor or cognitive priority group. The Timed-Up and Go (TUG) test is employed under both single and cognitive dual-task conditions (serial 3 subtraction). The motor dual-task effect, using stride length, and the cognitive dual-task effect, using the correct response rate of subtraction, are calculated. In the motor priority group, high-frequency rTMS targets the primary motor cortex of the lower limb, whereas the cognitive priority group receives rTMS over the left dorsolateral prefrontal cortex. The active comparator for each sub-study is bilateral rTMS of the primary motor cortex of the upper limb. Over 4 weeks, the participants will undergo 10 rTMS sessions, with evaluations conducted pre-intervention, mid-intervention, immediately post-intervention, and at 2-month follow-up. The primary outcome is a change in TUG time between the pre- and immediate post-intervention evaluations. The secondary outcome variables are the TUG under cognitive dual-task conditions, Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III, New Freezing of Gait Questionnaire, Digit Span, trail-making test, transcranial magnetic stimulation-induced motor-evoked potentials, diffusion tensor imaging, and resting state functional magnetic resonance imaging. DISCUSSION: The study will reveal the effect of personalized rTMS based on functional reserve compared to the conventional rTMS approach in PD. Furthermore, the findings of this study may provide empirical evidence for an rTMS protocol tailored to individual functional reserves to enhance ambulatory function in patients with PD. TRIAL REGISTRATION: ClinicalTrials.gov NCT06350617. Registered on 5 April 2024.

Oxazine drug-seed induces paraptosis and apoptosis through reactive oxygen species/JNK pathway in human breast cancer cells.

Small molecule-driven JNK activation has been found to induce apoptosis and paraptosis in cancer cells. Herein pharmacological effects of synthetic oxazine (4aS, 7aS)-3-((4-(4­chloro-2-fluorophenyl)piperazin-1-yl)methyl)-4-phenyl-4, 4a, 5, 6, 7, 7a-hexahydrocyclopenta[e] [1,2]oxazine (FPPO; BSO-07) on JNK-driven apoptosis and paraptosis has been demonstrated in human breast cancer (BC) MDA-MB231 and MCF-7 cells respectively. BSO-07 imparted significant cytotoxicity in BC cells, induced activation of JNK, and increased intracellular reactive oxygen species (ROS) levels. It also enhanced the expression of apoptosis-associated proteins like PARP, Bax, and phosphorylated p53, while decreasing the levels of Bcl-2, Bcl-xL, and Survivin. Furthermore, the drug altered the expression of proteins linked to paraptosis, such as ATF4 and CHOP. Treatment with N-acetyl-cysteine (antioxidant) or SP600125 (JNK inhibitor) partly reversed the effects of BSO-07 on apoptosis and paraptosis. Advanced in silico bioinformatics, cheminformatics, density Fourier transform and molecular electrostatic potential analysis further demonstrated that BSO-07 induced apoptosis and paraptosis via the ROS/JNK pathway in human BC cells.

Cryopreservation of neuroectoderm on a pillar plate and in situ differentiation into human brain organoids.

Cryopreservation in cryovials extends cell storage at low temperatures, and advances in organoid cryopreservation improve reproducibility and reduce generation time. However, cryopreserving human organoids presents challenges due to the limited diffusion of cryoprotective agents (CPAs) into the organoid core and the potential toxicity of these agents. To overcome these obstacles, we developed a cryopreservation technique using a pillar plate platform. To illustrate cryopreservation application to human brain organoids (HBOs), early-stage HBOs were produced by differentiating induced pluripotent stem cells (iPSCs) into neuroectoderm (NEs) in an ultralow atachement (ULA) 384-well plate. These NEs were transferred and encapsulated in Matrigel on the pillar plate. The early-stage HBOs on the pillar plate were exposed to four commercially available CPAs, including PSC cryopreservation kit, CryoStor CS10, 3dGRO, and 10% DMSO, before being frozen overnight at -80°C and subsequently stored in a liquid nitrogen dewar. We examined the impact of CPA type, organoid size, and CPA exposure duration on cell viability post-thaw. Additionally, the differentiation of early-stage HBOs on the pillar plate was assessed using RT-qPCR and immunofluorescence staining. The PSC cryopreservation kit proved to be the least toxic for preserving these HBOs on the pillar plate. Notably, smaller HBOs showed higher cell viability post-cryopreservation than larger ones. An incubation period of 80 minutes with the PSC kit was essential to ensure optimal CPA diffusion into HBOs with a diameter of 400 - 600 µm. These cryopreserved early-stage HBOs successfully matured over 30 days, exhibiting gene expression patterns akin to non-cryopreserved HBOs. The cryopreserved early-stage HBOs on the pillar plate maintained high viability after thawing and successfully differentiated into mature HBOs. This on-chip cryopreservation method could extend to other small organoids, by integrating cryopreservation, thawing, culturing, staining, rinsing, and imaging processes within a single system, thereby preserving the 3D structure of the organoids.

Effectiveness and Safety of Pharmacopuncture on Inpatients with Tension Headache Caused by Traffic Accidents: A Pragmatic Randomized Controlled Trial.

Background: This study investigated the effectiveness and safety of pharmacopuncture for pain relief and functional improvement in patients with traffic accident (TA)-induced acute tension headaches. Methods: The study employed a parallel, single-centered, pragmatic, randomized controlled trial design. Eighty patients complaining of acute tension headaches were randomized into the integrative Korean medicine treatment (IKM treatment) group and the pharmacopuncture group on suboccipital muscles (suboccipital muscles pharmacopuncture + IKM treatment), with 40 participants assigned to each group. The patients in the pharmacopuncture group underwent pharmacopuncture as an add-on therapy, consisting of three sessions. Both groups were reassessed 2 months post-intervention. To assess the outcomes, the Numeric Rating Scale (NRS) for Headache, NRS for Neck Pain, Headache Disability Index, Headache Impact Test-6, EuroQol 5-Dimension, and Patient Global Impression of Change were used. Results: The improvement in the outcomes of the pharmacopuncture group was significantly greater than that of the comparison group on day 4 of hospitalization in terms of pain (difference in NRS of headache -2.59, 95% CI -3.06 to -2.12; NRS of Neck pain -1.05, 95% CI -1.50 to -0.59) and function (difference in HDI -24.78, 95% CI, -31.79 to -17.76; HIT-6 -6.13, 95% CI, -9.47 to -2.78). Additionally, in 2 months of follow-up, the recovery rate of headache was significantly higher in the pharmacopuncture group than in the comparison group. Conclusions: The pharmacopuncture group demonstrated superior outcomes in symptom improvement than the comparison group did, providing insights into novel and useful applications of pharmacopuncture in the clinical practice of Korean medicine.

ATAD5 functions as a regulatory platform for Ub-PCNA deubiquitination.

Ubiquitination status of proliferating cell nuclear antigen (PCNA) is crucial for regulating DNA lesion bypass. After the resolution of fork stalling, PCNA is subsequently deubiquitinated, but the underlying mechanism remains undefined. We found that the N-terminal domain of ATAD5 (ATAD5-N), the largest subunit of the PCNA-unloading complex, functions as a scaffold for Ub-PCNA deubiquitination. ATAD5 recognizes DNA-loaded Ub-PCNA through distinct DNA-binding and PCNA-binding motifs. Furthermore, ATAD5 forms a heterotrimeric complex with UAF1-USP1 deubiquitinase, facilitating the deubiquitination of DNA-loaded Ub-PCNA. ATAD5 also enhances the Ub-PCNA deubiquitination by USP7 and USP11 through specific interactions. ATAD5 promotes the distinct deubiquitination process of UAF1-USP1, USP7, and USP11 for poly-Ub-PCNA. Additionally, ATAD5 mutants deficient in UAF1-binding had increased sensitivity to DNA-damaging agents. Our results ultimately reveal that ATAD5 and USPs cooperate to efficiently deubiquitinate Ub-PCNA prior to its release from the DNA in order to safely deactivate the DNA repair process.

Comparative analysis of molecular and histological glioblastomas: insights into prognostic variance.

PURPOSE: Whether molecular glioblastomas (GBMs) identify with a similar dismal prognosis as a "classical" histological GBM is controversial. This study aimed to compare the clinical, molecular, imaging, surgical factors, and prognosis between molecular GBMs and histological GBMs. METHODS: Retrospective chart and imaging review was performed in 983 IDH-wildtype GBM patients (52 molecular GBMs and 931 histological GBMs) from a single institution between 2005 and 2023. Propensity score-matched analysis was additionally performed to adjust for differences in baseline variables between molecular GBMs and histological GBMs. RESULTS: Molecular GBM patients were substantially younger (58.1 vs. 62.4, P = 0.014) with higher rate of TERTp mutation (84.6% vs. 50.3%, P < 0.001) compared with histological GBM patients. Imaging showed higher incidence of gliomatosis cerebri pattern (32.7% vs. 9.2%, P < 0.001) in molecular GBM compared with histological GBM, which resulted in lesser extent of resection (P < 0.001) in these patients. The survival was significantly better in molecular GBM compared to histological GBM (median OS 30.2 vs. 18.4 months, P = 0.001). The superior outcome was confirmed in propensity score analyses by matching histological GBM to molecular GBM (P < 0.001). CONCLUSION: There are distinct clinical, molecular, and imaging differences between molecular GBMs and histological GBMs. Our results suggest that molecular GBMs have a more favorable prognosis than histological GBMs.

Activation mechanism and novel binding sites of the BKCa channel activator CTIBD.

The large-conductance calcium-activated potassium (BKCa) channel, which is crucial for urinary bladder smooth muscle relaxation, is a potential target for overactive bladder treatment. Our prior work unveiled CTIBD as a promising BKCa channel activator, altering V 1/2 and G max This study investigates CTIBD's activation mechanism, revealing its independence from the Ca2+ and membrane voltage sensing of the BKCa channel. Cryo-electron microscopy disclosed that two CTIBD molecules bind to hydrophobic regions on the extracellular side of the lipid bilayer. Key residues (W22, W203, and F266) are important for CTIBD binding, and their replacement with alanine reduces CTIBD-mediated channel activation. The triple-mutant (W22A/W203A/F266A) channel showed the smallest V 1/2 shift with a minimal impact on activation and deactivation kinetics by CTIBD. At the single-channel level, CTIBD treatment was much less effective at increasing P o in the triple mutant, mainly because of a drastically increased dissociation rate compared with the WT. These findings highlight CTIBD's mechanism, offering crucial insights for developing small-molecule treatments for BKCa-related pathophysiological conditions.

A High Immediate Postoperative Systemic Immune-inflammation Index Is Associated With Postoperative Symptomatic Cerebral Infarction in Moyamoya Patients Undergoing Combined Revascularization Surgery.

BACKGROUND: Inflammation plays a role in the pathogenesis of cerebral infarction. Postoperative symptomatic cerebral infarction (SCI) is a complication after revascularization surgery in patients with moyamoya disease (MMD). We investigated the association between the systemic-immune-inflammation index (SII) and postoperative SCI during hospital stay in such patients. METHODS: Perioperative data were retrospectively obtained from 681 MMD patients who underwent revascularization surgery. SII cutoff values were identified as those where the sum of sensitivity and specificity associated with SCI were highest. Patients were divided into 4 subgroups according to the preoperative and immediate postoperative cutoff SII: HH (preoperative and postoperative SII high, n=22), LH (low preoperative and high postoperative SII, n=68), HL (high preoperative and low postoperative SII, n=125), and LL (preoperative and postoperative SII low, n=466). RESULTS: Postoperative SCI occurred in 54 (7.6%) patients. The cutoff values for preoperative and immediate postoperative SII were 641.3 and 1925.4, respectively. Postoperative SCI during hospital stay was more frequent in the high postoperative SII group than in the low postoperative SII group (25.6% vs. 4.9%; P<0.001). Multivariate analysis revealed that a high immediate postoperative SII was a predictor of postoperative SCI (odds ratio, 11.61; 95% CI: 5.20-26.00; P<0.001). Postoperative SCI was lower in group LL than in group LH (3.6% vs. 23.5%, P<0.008) and was lower in group HL than in groups HH and LH (9.6% vs. 31.8% and 23.5%, both P<0.05). CONCLUSIONS: A high immediate postoperative SII was associated with postoperative SCI during hospital stay in MMD patients who underwent revascularization surgery.

Pharmacodynamics Between a Dual Delayed-Release Formulation of Low-Dose Esomeprazole and Famotidine in Healthy Korean Subjects.

PURPOSE: Gastritis, one of the most common clinically diagnosed conditions, is defined as the infiltration of inflammatory cells into the gastric mucosa. Drugs for gastritis include histamine-2 receptor antagonists and proton pump inhibitors (PPIs), which reduce acidity in the stomach, and antacids, which neutralize acid. Esomeprazole is a PPI for gastroesophageal reflux disease and gastric and duodenal ulcers that has been shown to be safe and effective at a 10 mg dose. Dual-release drugs have not yet been approved for the treatment of gastritis domestically or internationally. In this study, a dual delayed-release (DR) esomeprazole (10 mg), was compared to famotidine (20 mg) to determine its effectiveness in the treatment of gastritis. METHODS: This study was a randomized, open-label, multiple-dose, 2-treatment, 2-period, 2-sequence crossover study with a 7-day washout between periods. In each period, the subjects were administered one dose of esomeprazole (10 mg) or famotidine (20 mg) for 7 days at each period. The 24-hour gastric pH was recorded after single and multiple doses. The percentage of time (duration%) that the pH was maintained above 4 in the 24 hours after 7 days of repeated dosing was evaluated. FINDINGS: The mean percentages of time that the gastric pH was above 4 after multiple doses over 7 days of a dual DR esomeprazole (10 mg) and famotidine (20 mg) was 47.31% ± 14.85% and 23.88% ± 10.73%. IMPLICATIONS: Multiple doses of a dual DR esomeprazole (10 mg) showed effective gastric acid secretion suppression compared to famotidine with comparable safety and tolerability. These results provide evidence supporting the clinical use of a dual DR esomeprazole (10 mg) to treat gastritis. CLINICALTRIALS: gov identifier: NCT04967014.

Analysis of YouTube-Based Therapeutic Content for Children with Cerebral Palsy.

BACKGROUND/OBJECTIVES: Cerebral palsy (CP) causes movement and posture challenges due to central nervous system damage, requiring lifelong management. During the COVID-19 pandemic, there was limited access to facility-based treatments, which increased the demand for home-based therapies and digital resources. We analyzed the qualitative and quantitative aspects of YouTube videos focusing on CP therapy for children. METHODS: A total of 95 videos were evaluated for content quality using the modified DISCERN (mDISCERN) tool and Global Quality Scale (GQS). The therapeutic program efficacy was assessed via the International Consensus on Therapeutic Exercise and Training (i-CONTENT) tool, Consensus on Therapeutic Exercise Training (CONTENT) scale, and Consensus on Exercise Reporting Template (CERT), and popularity was measured by the video power index (VPI). RESULTS: YouTube-based therapeutic videos for children with CP generally exhibit reliability in video content and effectiveness in therapeutic programming, and no correlations were found between video popularity and quality. However, the qualitative analysis reveals insufficient mention of uncertainty in the treatment principles within the video content as well as a lack of detailed treatment descriptions encompassing aspects such as intensity, frequency, timing, setting, outcome measurement during and post-treatment, and safety considerations within therapeutic programs. In particular, this tendency was consistent regardless of the uploader's expertise level and the classification of the neuromotor therapy type in contrast to that of the exercise type. CONCLUSIONS: YouTube-based content for CP children still has significant limitations in how substantive viewers, such as caregivers, can acquire tailored information and apply practical information to their exercise and treatment programs.

Efficacy of personalized rTMS to enhance upper limb function in subacute stroke patients: a protocol for a multi-center, randomized controlled study.

Background: Repetitive transcranial magnetic stimulation (rTMS) is widely used therapy to enhance motor deficit in stroke patients. To date, rTMS protocols used in stroke patients are relatively unified. However, as the pathophysiology of stroke is diverse and individual functional deficits are distinctive, more precise application of rTMS is warranted. Therefore, the objective of this study was to determine the effects of personalized protocols of rTMS therapy based on the functional reserve of each stroke patient in subacute phase. Methods: This study will recruit 120 patients with stroke in subacute phase suffering from the upper extremity motor impairment, from five different hospitals in Korea. The participants will be allocated into three different study conditions based on the functional reserve of each participant, measured by the results of TMS-induced motor evoked potentials (MEPs), and brain MRI with diffusion tensor imaging (DTI) evaluations. The participants of the intervention-group in the three study conditions will receive different protocols of rTMS intervention, a total of 10 sessions for 2 weeks: high-frequency rTMS on ipsilesional primary motor cortex (M1), high-frequency rTMS on ipsilesional ventral premotor cortex, and high-frequency rTMS on contralesional M1. The participants of the control-group in all three study conditions will receive the same rTMS protocol: low-frequency rTMS on contralesional M1. For outcome measures, the following assessments will be performed at baseline (T0), during-intervention (T1), post-intervention (T2), and follow-up (T3) periods: Fugl-Meyer Assessment (FMA), Box-and-block test, Action Research Arm Test, Jebsen-Taylor hand function test, hand grip strength, Functional Ambulatory Category, fractional anisotropy measured by the DTI, and brain network connectivity obtained from MRI. The primary outcome will be the difference of upper limb function, as measured by FMA from T0 to T2. The secondary outcomes will be the differences of other assessments. Discussion: This study will determine the effects of applying different protocols of rTMS therapy based on the functional reserve of each patient. In addition, this methodology may prove to be more efficient than conventional rTMS protocols. Therefore, effective personalized application of rTMS to stroke patients can be achieved based on their severity, predicted mechanism of motor recovery, or functional reserves. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT06270238.

Effects of mHealth Practice Patterns on Improving Metabolic Syndrome Using the Information-Motivation-Behavioral Skills Model.

Chronic diseases contribute to 68% of global mortality, highlighting the importance of early detection and management of conditions such as metabolic syndrome. Effective lifestyle interventions, particularly through mobile health (mHealth), have shown potential in promoting health and reducing cardiometabolic risk. This study utilized mHealth data from public health centers in South Korea, targeting adults with risk factors for metabolic syndrome. The Intervention-Motivation-Behavioral skills (IMB) theoretical model was applied to categorize participants' practice patterns over time using the Group-Based Trend Model (GBTM). And the Generalized Estimating Equations (GEE) methodology was applied to confirm the effective practice patterns for improving metabolic syndrome. Data were collected over 24 weeks. The dataset encompasses life-log data capable of capturing changes in intervention, self-report surveys, and clinical measurements, all linked to personal identification keys and thereby integrated. Participants demonstrated improved health behaviors, with the healthy eating score increasing from 5.0 to 6.4 and physical activity rates rising from 41.5% to 59%. Health risk factors decreased significantly, with the mean number of risk factors dropping from 2.4 to 1.4. The percentage of subjects with three or more metabolic syndrome components decreased from 42.3% in the initial period to 19.2% in the final period. Practice patterns by IMB components were classified into three categories: continuous type, late decline type, and early decline type. Improvements in health behavior and metabolic syndrome were observed in the continuous type of each IMB component. The mHealth interventions were confirmed to be positively associated with improved health behavior and management of metabolic syndrome in the continuous practice patterns of IMB.

Interdisciplinary treatment of a mutilated dentition with multiple missing teeth and horizontal impaction of a mandibular third molar using an orthodontic skeletal anchorage and dental implants-Case report.

OBJECTIVE: This case report presents a female adult patient who exhibits poor oral hygiene, a mutilated dentition with multiple missing teeth, and skeletal asymmetry. CLINICAL CONSIDERATIONS: Interdisciplinary treatment was necessary to maintain oral hygiene, treat caries, extract residual roots, and upright a horizontally impacted third molar using a miniplate. Additionally, orthodontic mini-implants were utilized as anchorage to improve sagittal relationship and space closing. Space management was completed with orthodontic treatment, followed by restoration of the multiple missing teeth with dental implants. CONCLUSION: Consequently, an esthetic smile and functional occlusion were achieved by interdisciplinary treatment using orthodontic skeletal anchorage devices and dental implants. CLINICAL SIGNIFICANCE: Missing mandibular first molar spaces were closed with retraction of the anterior teeth and protraction of the mandibular second molars using orthodontic mini-implants. The mandibular right third molar, which should have erupted, was protracted with the second molar, while the horizontally impacted mandibular left third molar was uprighted using a miniplate and was protracted with an orthodontic mini-implant. The missing maxillary lateral incisors were replaced with the maxillary canines, and the maxillary canines were replaced with the maxillary first premolars. The missing maxillary right second premolar and first molar and left first and second molars were successfully restored with dental implants.

Identification of prognostic imaging biomarkers in H3 K27-altered diffuse midline gliomas in adults: impact of tumor oxygenation imaging biomarkers on survival.

PURPOSE: To investigate prognostic markers for H3 K27-altered diffuse midline gliomas (DMGs) in adults with clinical, qualitative and quantitative imaging phenotypes, including tumor oxygenation characteristics. METHODS: Retrospective chart and imaging reviews were conducted on 32 adults with H3 K27-altered DMGs between 2017 and 2023. Clinical and qualitative imaging characteristics were analyzed. Quantitative imaging assessment was performed from the tumor mask via automatic segmentation to calculate normalized cerebral blood volume (nCBV), capillary transit time heterogeneity (CTH), oxygen extraction fraction (OEF), relative cerebral metabolic rate of oxygen (rCMRO2), and mean ADC values. Leptomeningeal metastases (LM) was diagnosed with imaging. Cox analyses were conducted to determine predictors of overall survival (OS) in entire patients and a subgroup of patients with contrast-enhancing (CE) tumor. RESULTS: The median patient age was 40.5 years (range 19.9-75.7), with an OS of 30.3 months (interquartile range 11.3-32.3). In entire patients, the presence of LM was the only independent predictor of OS (hazard ratio [HR] = 6.01, P = 0.009). In the subgroup of 23 (71.9%) patients with CE tumors, rCMRO2 of CE tumor (HR = 1.08, P = 0.019) and the presence of LM (HR = 5.92, P = 0.043) were independent predictors of OS. CONCLUSION: The presence of LM was independently associated with poor prognosis in adult patients with H3 K27-altered DMG. In patients with CE tumors, higher rCMRO2 of CE tumor, which may reflect higher metabolic activity in the tumor oxygenation microenvironment, may be a useful imaging biomarker to predict poor prognosis.

Leptomeningeal Metastases in IDH-wildtype Glioblastomas Revisited: Comprehensive Analysis of Incidence, Risk Factors, and Prognosis Based on Post-contrast FLAIR.

BACKGROUND: The incidence of leptomeningeal metastases (LM) has been reported diversely. This study aimed to investigate the incidence, risk factors, and prognosis of LM in patients with IDH-wildtype glioblastoma. METHODS: A total of 828 patients with IDH-wildtype glioblastoma were enrolled between 2005 and 2022. Baseline preoperative MRI including post-contrast fluid-attenuated inversion recovery (FLAIR) was used for LM diagnosis. Qualitative and quantitative features, including distance between tumor and subventricular zone (SVZ) and tumor volume by automatic segmentation of the lateral ventricles and tumor, were assessed. Logistic analysis of LM development was performed using clinical, molecular, and imaging data. Survival analysis was performed. RESULTS: The incidence of LM was 11.4%. MGMTp unmethylation (odds ratio [OR] = 1.92, P = 0.014), shorter distance between tumor and SVZ (OR = 0.94, P = 0.010), and larger contrast-enhancing tumor volume (OR = 1.02, P < 0.001) were significantly associated with LM. The overall survival (OS) was significantly shorter in patients with LM than in those without (log-rank test; P < 0.001), with median OS of 12.2 and 18.5 months, respectively. Presence of LM remained an independent prognostic factor for OS in IDH-wildtype glioblastoma (hazard ratio = 1.42, P = 0.011), along with other clinical, molecular, imaging, and surgical prognostic factors. CONCLUSION: The incidence of LM is high in patients with IDH-wildtype glioblastoma, and aggressive molecular and imaging factors are correlated with LM development. The prognostic significance of LM based on post-contrast FLAIR imaging suggests acknowledgement of post-contrast FLAIR as a reliable diagnostic tool for clinicians.

One-year mortality and readmission risks following hospitalization for acute exacerbation of chronic obstructive pulmonary disease based on the types of acute respiratory failure: An observational study.

Few studies have examined the risk factors associated with the type of acute respiratory failure (ARF) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). This study evaluated the clinical characteristics and prognosis of patients hospitalized for acute exacerbation of COPD based on the type of ARF. The medical charts of hospitalized patients with acute exacerbation of COPD between 2016 and 2021 were retrospectively reviewed. We classified ARF into 2 types: type 1 ARF with PaO2 < 60 mm Hg in room air or a ratio of arterial partial pressure to fractional inspired oxygen < 300, and type 2 ARF with PaCO2 > 45 mm Hg and arterial pH < 7.35. A total of 435 patients were enrolled in study, including 170 participants without ARF, 165 with type 1 ARF, and 100 with type 2 ARF. Compared with the non-ARF group, the frequency of high-flow nasal cannula, noninvasive ventilation, intensive care unit admissions, and in-hospital deaths was higher in the ARF group compared with the non-ARF group. The ARF group had higher 1-year mortality group (hazard ratio [HR], 2.809; 95% confidence interval [CI], 1.099-7.180; P = .031) and readmission within 1-year rates (HR, 1.561; 95% CI, 1.061-2.295; P = .024) than the non-ARF group. The type 1 ARF group had a higher risk of 1-year mortality (HR, 3.022; 95% CI, 1.041-8.774; P = .042) and hospital readmission within 1-year (HR, 2.053; 95% CI, 1.230-3.428; P = .006) compared with the non-ARF group. There was no difference in mortality and readmission rates between the type 1 and type 2 ARF groups. In conclusion, patients with type 1 ARF rather than type 2 ARF had higher mortality and readmission rates than those without ARF. The prognoses of patients with type 1 and type 2 ARF were similar.

Interplay between YAP/TAZ and metabolic dysfunction-associated steatotic liver disease progression.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming an increasingly pressing global health challenge, with increasing mortality rates showing an upward trend. Two million deaths occur annually from cirrhosis and liver cancer together each year. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key effectors of the Hippo signaling pathway, critically regulate tissue homeostasis and disease progression in the liver. While initial studies have shown that YAP expression is normally restricted to cholangiocytes in healthy livers, the activation of YAP/TAZ is observed in other hepatic cells during chronic liver disease. The disease-driven dysregulation of YAP/TAZ appears to be a critical element in the MASLD progression, contributing to hepatocyte dysfunction, inflammation, and fibrosis. In this study, we focused on the complex roles of YAP/TAZ in MASLD and explored how the YAP/TAZ dysregulation of YAP/TAZ drives steatosis, inflammation, fibrosis, and cirrhosis. Finally, the cell-type-specific functions of YAP/TAZ in different types of hepatic cells, such as hepatocytes, hepatic stellate cells, hepatic macrophages, and biliary epithelial cells are discussed, highlighting the multifaceted impact of YAP/TAZ on liver physiology and pathology.

Blood Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Promising Screening Biomarkers for Brain Metastases in Patients with Lung Cancer.

The diagnosis of brain metastases (BMs) in patients with lung cancer (LC) predominantly relies on magnetic resonance imaging (MRI), a method that is constrained by high costs and limited accessibility. This study explores the potential of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) as screening biomarkers for BMs in LC patients. We conducted a retrospective analysis of 700 LC cases at the National Cancer Center, Korea, from July 2020 to June 2022, measuring sNfL and sGFAP levels at initial LC diagnosis. The likelihood of BM was evaluated using multivariate analysis and a predictive nomogram. Additionally, we prospectively monitored 177 samples from 46 LC patients initially without BM. Patients with BMs (n= 135) had significantly higher median sNfL (52.5 pg/mL) and sGFAP (239.2 pg/mL) levels compared to those without BMs (n = 565), with medians of 17.8 pg/mL and 141.1 pg/mL, respectively (p < 0.001 for both). The nomogram, incorporating age, sNfL, and sGFAP, predicted BM with an area under the curve (AUC) of 0.877 (95% CI 0.84-0.914), showing 74.8% sensitivity and 83.5% specificity. Over nine months, 93% of samples from patients without BM remained below the cutoff, while all patients developing BMs showed increased levels at detection. A nomogram incorporating age, sNfL, and sGFAP provides a valuable tool for identifying LC patients at high risk for BM, thereby enabling targeted MRI screenings and enhancing diagnostic efficiency.

Evaluation of the Clinical Efficacy and Trust in AI-Assisted Embryo Ranking: Survey-Based Prospective Study.

BACKGROUND: Current embryo assessment methods for in vitro fertilization depend on subjective morphological assessments. Recently, artificial intelligence (AI) has emerged as a promising tool for embryo assessment; however, its clinical efficacy and trustworthiness remain unproven. Simulation studies may provide additional evidence, provided that they are meticulously designed to mitigate bias and variance. OBJECTIVE: The primary objective of this study was to evaluate the benefits of an AI model for predicting clinical pregnancy through well-designed simulations. The secondary objective was to identify the characteristics of and potential bias in the subgroups of embryologists with varying degrees of experience. METHODS: This simulation study involved a questionnaire-based survey conducted on 61 embryologists with varying levels of experience from 12 in vitro fertilization clinics. The survey was conducted via Google Forms (Google Inc) in three phases: (1) phase 1, an initial assessment (December 23, 2022, to January 22, 2023); (2) phase 2, a validation assessment (March 6, 2023, to April 5, 2023); and (3) phase 3 an AI-guided assessment (March 6, 2023, to April 5, 2023). Inter- and intraobserver assessments and the accuracy of embryo selection from 360 day-5 embryos before and after AI guidance were analyzed for all embryologists and subgroups of senior and junior embryologists. RESULTS: With AI guidance, the interobserver agreement increased from 0.355 to 0.527 and from 0.440 to 0.524 for junior and senior embryologists, respectively, thus reaching similar levels of agreement. In a test of accurate embryo selection with 90 questions, the numbers of correct responses by the embryologists only, embryologists with AI guidance, and AI only were 34 (38%), 45 (50%), and 59 (66%), respectively. Without AI, the average score (accuracy) of the junior group was 33.516 (37%), while that of the senior group was 35.967 (40%), with P<.001 in the t test. With AI guidance, the average score (accuracy) of the junior group increased to 46.581 (52%), reaching a level similar to that of the senior embryologists of 44.833 (50%), with P=.34. Junior embryologists had a higher level of trust in the AI score. CONCLUSIONS: This study demonstrates the potential benefits of AI in selecting embryos with high chances of pregnancy, particularly for embryologists with 5 years or less of experience, possibly due to their trust in AI. Thus, using AI as an auxiliary tool in clinical practice has the potential to improve embryo assessment and increase the probability of a successful pregnancy.