Identification of molecular subtypes of dementia by using blood-proteins interaction-aware graph propagational network.

Plasma protein biomarkers have been considered promising tools for diagnosing dementia subtypes due to their low variability, cost-effectiveness, and minimal invasiveness in diagnostic procedures. Machine learning (ML) methods have been applied to enhance accuracy of the biomarker discovery. However, previous ML-based studies often overlook interactions between proteins, which are crucial in complex disorders like dementia. While protein-protein interactions (PPIs) have been used in network models, these models often fail to fully capture the diverse properties of PPIs due to their local awareness. This drawback increases the chance of neglecting critical components and magnifying the impact of noisy interactions. In this study, we propose a novel graph-based ML model for dementia subtype diagnosis, the graph propagational network (GPN). By propagating the independent effect of plasma proteins on PPI network, the GPN extracts the globally interactive effects between proteins. Experimental results showed that the interactive effect between proteins yielded to further clarify the differences between dementia subtype groups and contributed to the performance improvement where the GPN outperformed existing methods by 10.4% on average.

Boc Protection for Diamine-Appended MOF Adsorbents to Enhance CO2 Recyclability under Realistic Humid Conditions.

Among the various metal-organic framework (MOF) adsorbents, diamine-functionalized Mg2(dobpdc) (dobpdc4- = 4,4-dioxidobiphenyl-3,3'-dicarboxylate) shows remarkable carbon dioxide removal performance. However, applying diamine-functionalized Mg2(dobpdc) in practical applications is premature because it shows persistent performance degradation under real flue gas conditions containing water vapor owing to diamine loss during wet cycles. To address this issue, we employed hydrophobic carbonate compounds to protect diamine groups in een-Mg2(dobpdc) (een-MOF, een = N-ethylethylenediamine). tert-Butyl dicarbonate (Boc) reacted rapidly with diamines at the pore openings of MOF particles to form dense secondary and tertiary hydrophobic amines, effectively preventing moisture ingress. The Boc-protected een-MOF-Boc1 maintained excellent CO2 adsorption even under simulated flue gas conditions containing 10% H2O. This observation indicates that Boc protection renders een groups intact during repeated wet cycles, suggesting that Boc-protected een groups are resistant to replacement by water molecules. To increase the practicability of the MOF adsorbent, we fabricated een-MOF/PAN-Boc1 composite beads by shaping MOF particles with polyacrylonitrile (PAN). Notably, the composite beads maintained their CO2 adsorption performance even after repeating the temperature swing adsorption process more than 150 times in 10% water vapor. Furthermore, breakthrough tests showed that the dynamic CO2 separation performance was retained under humid conditions. These results demonstrate that Boc protection provides an easy and effective way to develop promising adsorbents with high CO2 adsorption capacity, long-term durability, and the properties required for postcombustion applications.

Extended MOF-74-Type Variant with an Azine Linkage: Efficient Direct Air Capture and One-Pot Synthesis.

Direct air capture (DAC) shows considerable promise for the effective removal of CO2; however, materials applicable to DAC are lacking. Among metal-organic framework (MOF) adsorbents, diamine-Mg2(dobpdc) (dobpdc4- = 4,4-dioxidobiphenyl-3,3'-dicarboxylate) effectively removes low-pressure CO2, but the synthesis of the organic ligand requires high temperature, high pressure, and a toxic solvent. Besides, it is necessary to isolate the ligand for utilization in the synthesis of the framework. In this study, we synthesized a new variant of extended MOF-74-type frameworks, M2(hob) (M = Mg2+, Co2+, Ni2+, and Zn2+; hob4- = 5,5'-(hydrazine-1,2-diylidenebis(methanylylidene))bis(2-oxidobenzoate)), constructed from an azine-bonded organic ligand obtained through a facile condensation reaction at room temperature. Functionalization of Mg2(hob) with N-methylethylenediamine, N-ethylethylenediamine, and N,N'-dimethylethylenediamine (mmen) enables strong interactions with low-pressure CO2, resulting in top-tier adsorption capacities of 2.60, 2.49, and 2.91 mmol g-1 at 400 ppm of CO2, respectively. Under humid conditions, the CO2 capacity was higher than under dry conditions due to the presence of water molecules that aid in the formation of bicarbonate species. A composite material combining mmen-Mg2(hob) and polyvinylidene fluoride, a hydrophobic polymer, retained its excellent adsorption performance even after 7 days of exposure to 40% relative humidity. In addition, the one-pot synthesis of Mg2(hob) from a mixture of the corresponding monomers is achieved without separate ligand synthesis steps; thus, this framework is suitable for facile large-scale production. This work underscores that the newly synthesized Mg2(hob) and its composites demonstrate significant potential for DAC applications.

Polygenic risk score of metabolic dysfunction-associated steatotic liver disease amplifies the health impact on severe liver disease and metabolism-related outcomes.

BACKGROUND: Although the inherited risk factors associated with fatty liver disease are well understood, little is known about the genetic background of metabolic dysfunction-associated steatotic liver disease (MASLD) and its related health impacts. Compared to non-alcoholic fatty liver disease (NAFLD), MASLD presents significantly distinct diagnostic criteria, and epidemiological and clinical features, but the related genetic variants are yet to be investigated. Therefore, we conducted this study to assess the genetic background of MASLD and interactions between MASLD-related genetic variants and metabolism-related outcomes. METHODS: Participants from the UK Biobank were grouped into discovery and replication cohorts for an MASLD genome-wide association study (GWAS), and base and target cohorts for polygenic risk score (PRS) analysis. Autosomal genetic variants associated with NAFLD were compared with the MASLD GWAS results. Kaplan-Meier and Cox regression analyses were used to assess associations between MASLD and metabolism-related outcomes. RESULTS: Sixteen single-nucleotide polymorphisms (SNPs) were identified at genome-wide significance levels for MASLD and duplicated in the replication cohort. Differences were found after comparing these SNPs with the results of NAFLD-related genetic variants. MASLD cases with high PRS had a multivariate-adjusted hazard ratio of 3.15 (95% confidence interval, 2.54-3.90) for severe liver disease (SLD), and 2.81 (2.60-3.03) for type 2 diabetes mellitus. The high PRS amplified the impact of MASLD on SLD and extrahepatic outcomes. CONCLUSIONS: High PRS of MASLD GWAS amplified the impact of MASLD on SLD and metabolism-related outcomes, thereby refining the process of identification of individuals at high risk of MASLD. Supplementation of this process with relevant genetic backgrounds may lead to more effective MASLD prevention and management.

Lower creatinine to cystatin C ratio is associated with an increased risk of MASLD: A cross-sectional and prospective study of 368,634 UK Biobank participants.

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects many populations, and screening out the high-risk populations at an early stage is a challenge. As a sarcopenia index, the relationship between creatinine to cystatin C ratio (CCR) and MASLD remains unclear. This cross-sectional, prospective study aimed to explore the relationship between CCR and MASLD. Design Firstly, explored the correlation between CCR and MASLD in cross-sectional analyses. Then excluded the population with baseeline diagnosis of MASLD and analyzed the association with baseline CCR levels and the onset of MASLD in the population with available follow-up data. Univariate and multivariate logistic regression analyses were used to calculate odds ratios (ORs) to evaluate the association between CCR levels and MASLD. PATIENTS AND MEASUREMENTS: This study included 368,634 participants from the UK Biobank for cross-sectional and prospective analyses. The demographic characteristics and laboratory measurements of all participants were obtained from the UK Biobank. MASLD was diagnosed according to the multi-society consensus nomenclature. Hepatic steatosis was defined as FLI  ≥60. RESULTS: We grouped the study participants according to CCR tertiles. In cross-sectional analyses, participants in CCR tertile 1 had the highest MASLD risk (OR: 1.070, 95% CI: 1.053-1.088, p < .001). And the similar association was observed in the prospective analyses (CCR tertile 1 OR: 1.340, 95% CI: 1.077-1.660, p = .009; CCR tertile 2 OR: 1.217, 95% CI: 1.021-1.450, p = .029, respectively). After stratification by gender, the significant association between CCR and the onset of MASLD was only observed in males (CCR tertile 1 OR: 1.639, 95% CI: 1.160-2.317, p = .005; CCR tertile 2 OR: 1.322, 95% CI: 1.073-1.628, p = .005, respectively). CONCLUSION: Our results indicated that lower CCR was significantly associated with higher risk of MASLD, based on which predictive models can be developed to screen populations at high risk of developing MASLD.

Association between fatty liver index and controlled attenuation parameters as markers of metabolic dysfunction-associated fatty liver disease and bone mineral density: observational and two-sample Mendelian randomization studies.

Previously observational studies did not draw a clear conclusion on the association between fatty liver diseases and bone mineral density (BMD). Our large-scale studies revealed that MAFLD and hepatic steatosis had no causal effect on BMD, while some metabolic factors were correlated with BMD. The findings have important implications for the relationship between fatty liver diseases and BMD, and may help direct the clinical management of MAFLD patients who experience osteoporosis and osteopenia. PURPOSE: Liver and bone are active endocrine organs with several metabolic functions. However, the link between metabolic dysfunction-associated fatty liver disease (MAFLD) and bone mineral density (BMD) is contradictory. METHODS: Using the UK Biobank and National Health and Nutrition Examination Survey (NHANES) dataset, we investigated the association between MAFLD, steatosis, and BMD in the observational analysis. We performed genome-wide association analysis to identify single-nucleotide polymorphisms associated with MAFLD. Large-scale two-sample Mendelian randomization (TSMR) analyses examined the potential causal relationship between MAFLD, hepatic steatosis, or major comorbid metabolic factors, and BMD. RESULTS: After adjusting for demographic factors and body mass index, logistic regression analysis demonstrated a significant association between MAFLD and reduced heel BMD. However, this association disappeared after adjusting for additional metabolic factors. MAFLD was not associated with total body, femur neck, and lumbar BMD in the NHANES dataset. Magnetic resonance imaging-measured steatosis did not show significant associations with reduced total body, femur neck, and lumbar BMD in multivariate analysis. TSMR analyses indicated that MAFLD and hepatic steatosis were not associated with BMD. Among all MAFLD-related comorbid factors, overweight and type 2 diabetes showed a causal relationship with increased BMD, while waist circumference and hyperlipidemia had the opposite effect. CONCLUSION: No causal effect of MAFLD and hepatic steatosis on BMD was observed in this study, while some metabolic factors were correlated with BMD. This has important implications for understanding the relationship between fatty liver disease and BMD, which may help direct the clinical management of MAFLD patients with osteoporosis.

Evaluation of an artificial intelligence-based clinical trial matching system in Chinese patients with hepatocellular carcinoma: a retrospective study.

BACKGROUND: Artificial intelligence (AI)-assisted clinical trial screening is a promising prospect, although previous matching systems were developed in English, and relevant studies have only been conducted in Western countries. Therefore, we evaluated an AI-based clinical trial matching system (CTMS) that extracts medical data from the electronic health record system and matches them to clinical trials automatically. METHODS: This study included 1,053 consecutive inpatients primarily diagnosed with hepatocellular carcinoma who were referred to the liver tumor center of an academic medical center in China between January and December 2019. The eligibility criteria extracted from two clinical trials, patient attributes, and gold standard were decided manually. We evaluated the performance of the CTMS against the established gold standard by measuring the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and run time required. RESULTS: The manual reviewers demonstrated acceptable interrater reliability (Cohen's kappa 0.65-0.88). The performance results for the CTMS were as follows: accuracy, 92.9-98.0%; sensitivity, 51.9-83.5%; specificity, 99.0-99.1%; PPV, 75.7-85.1%; and NPV, 97.4-98.9%. The time required for eligibility determination by the CTMS and manual reviewers was 2 and 150 h, respectively. CONCLUSIONS: We found that the CTMS is particularly reliable in excluding ineligible patients in a significantly reduced amount of time. The CTMS excluded ineligible patients for clinical trials with good performance, reducing 98.7% of the work time. Thus, such AI-based systems with natural language processing and machine learning have potential utility in Chinese clinical trials.

Prospective longitudinal analysis of imaging-based spatiotemporal tumor habitats in glioblastoma, IDH-wild type: implication in patient outcome using multiparametric physiologic MRI.

BACKGROUND: Physiologic MRI-based tumor habitat analysis has the potential to predict patient outcomes by identifying the spatiotemporal habitats of glioblastoma. This study aims to prospectively validate the cut-off for tumor progression obtained from tumor habitat analysis based on physiologic MRI in ascertaining time-to-progression (TTP) and the site of progression in glioblastoma patients following concurrent chemoradiotherapy (CCRT). METHODS: In this prospective study (ClinicalTrials.gov ID: NCT02613988), we will recruit patients with IDH-wild type glioblastoma who underwent CCRT and obtained immediate post-operative and three serial post-CCRT MRI scans within a three-month interval, conducted using diffusion-weighted imaging and dynamic susceptibility contrast imaging. Voxels from cerebral blood volume and apparent diffusion coefficient maps will be grouped using k-means clustering into three spatial habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue). The spatiotemporal habitats of the tumor will be evaluated by comparing changes in each habitat between the serial MRI scans (post-operative and post-CCRT #1, #2, and #3). Associations between spatiotemporal habitats and TTP will be analyzed using cox proportional hazard modeling. The site of progression will be matched with spatiotemporal habitats. DISCUSSION: The perfusion- and diffusion-derived tumor habitat in glioblastoma is expected to stratify TTP and may serve as an early predictor for tumor progression in patients with IDH wild-type glioblastoma. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02613988.

Assessment of ATP metabolism to adenosine by ecto-nucleotidases carried by tumor-derived small extracellular vesicles.

Immunosuppression is a hallmark of cancer progression. Tumor-derived small extracellular vesicles (sEV), also known as TEX, produce adenosine (ADO) and can mediate tumor-induced immunosuppression.Here, the ATP pathway of ADO production (ATP →  ADP →  AMP →  ADO) by ecto-nucleotidases carried on the sEV surface was evaluated by a method using N6-etheno-ATP (eATP) and N6-etheno-AMP (eAMP) as substrates for enzymatic activity. The "downstream" N6-etheno-purines (ePurines) were measured by high performance liquid chromatography with fluorescence detection (HPLC-FL).Human melanoma cell-derived TEX (MTEX) metabolized eATP to N6-etheno-ADP (eADP), eAMP and N6-etheno-Adenosine (eADO) more robustly than control keratinocyte cell-derived sEV (CEX); due to accelerated conversion of eATP to eADP and eADP to eAMP. MTEX and CEX similarly metabolized eAMP to eADO. Blocking of the ATP pathway with the selective CD39 inhibitor ARL67156 or pan ecto-nucleotidase inhibitor POM-1 normalized the ATP pathway but neither inhibitor completely abolished it. In contrast, inhibition of CD73 by PSB12379 or AMPCP abolished eADO formation by both MTEX and CEX, suggesting that targeting CD73 is the preferred approach to eliminating ADO produced by ecto-nucleotidases located on the sEV surface.The noninvasive, sensitive, and specific assay assessing ePurine metabolism ± ecto-nucleotidase inhibitors in TEX enables the personalized identification of ecto-nucleotidase activity primarily involved in ADO production in patients with cancer. The assay could guide precision medicine by determining which purine is the preferred target for inhibitory therapeutic interventions.

Artemisinin inhibits neuronal ferroptosis in Alzheimer's disease models by targeting KEAP1.

Ferroptosis, a form of cell death characterized by lipid peroxidation, is involved in neurodegenerative diseases such as Alzheimer´s disease (AD). Recent studies have shown that a first-line antimalarial drug artemisinin is effective to counteract AD pathology. In this study, we investigated the protective effect of artemisinin against neuronal ferroptosis and the underlying mechanisms. In hippocampal HT22 cells, pretreatment with artemisinin dose-dependently protected against Erastin-induced cell death with an EC50 value of 5.032 µM, comparable to the ferroptosis inhibitor ferrostatin-1 (EC50 = 4.39 µM). We demonstrated that artemisinin (10 µM) significantly increased the nuclear translocation of Nrf2 and upregulated SLC7A11 and GPX4 in HT22 cells. Knockdown of Nrf2, SLC7A11 or GPX4 prevented the protective action of artemisinin, indicating that its anti-ferroptosis effect is mediated by the Nrf2-SLC7A11-GPX4 pathway. Molecular docking and Co-Immunoprecipitation (Co-IP) analysis revealed that artemisinin competitively binds with KEAP1, promoting the dissociation of KEAP1-Nrf2 complex and inhibiting the ubiquitination of Nrf2. Intrahippocampal injection of imidazole-ketone-Erastin (IKE) induced ferroptosis in mice accompanied by cognitive deficits evidenced by lower preference for exploration of new objects and new object locations in the NOR and NOL tests. Artemisinin (5, 10 mg/kg, i.p.) dose-dependently inhibited IKE-induced ferroptosis in hippocampal CA1 region and ameliorated learning and memory impairments. Moreover, we demonstrated that artemisinin reversed Aß1-42-induced ferroptosis, lipid peroxidation and glutathione depletion in HT22 cells, primary hippocampal neurons, and 3×Tg mice via the KEAP1-Nrf2 pathway. Our results demonstrate that artemisinin is a novel neuronal ferroptosis inhibitor that targets KEAP1 to activate the Nrf2-SLC7A11-GPX4 pathway.

Improved positional accuracy of dental implant placement using a haptic and machine-vision-controlled collaborative surgery robot: A pilot randomized controlled trial.

AIM: To compare the implant accuracy, safety and morbidity between robot-assisted and freehand dental implant placement. MATERIALS AND METHODS: Subjects requiring single-site dental implant placement were recruited. Patients were randomly allocated to freehand implant placement and robot-assisted implant placement. Differences in positional accuracy of the implant, surgical morbidity and complications were assessed. The significance of intergroup differences was tested with an intention-to-treat analysis and a per-protocol (PP) analysis (excluding one patient due to calibration error). RESULTS: Twenty patients (with a median age of 37, 13 female) were included. One subject assigned to the robotic arm was excluded from the PP analysis because of a large calibration error due to the dislodgement of the index. For robot-assisted and freehand implant placement, with the PP analysis, the median (25th-75th percentile) platform global deviation, apex global deviation and angular deviation were 1.23 (0.9-1.4) mm/1.9 (1.2-2.3) mm (p = .03, the Mann-Whitney U-test), 1.40 (1.1-1.6) mm/2.1 (1.7-3.9) mm (p < .01) and 3.0 (0.9-6.0)°/6.7 (2.2-13.9)° (p = .08), respectively. Both methods showed limited damage to the alveolar ridge and had similar peri- and post-operative morbidity and safety. CONCLUSIONS: Robot-assisted implant placement enabled greater positional accuracy of the implant compared to freehand placement in this pilot trial. The robotic system should be further developed to simplify surgical procedures and improve accuracy and be validated in properly sized trials assessing the full spectrum of relevant outcomes.

Comparison of Different Intraoral Scanners With Prefabricated Aid on Accuracy and Framework Passive Fit of Digital Complete-Arch Implant Impression: An In Vitro Study.

OBJECTIVES: This study aimed to compare the accuracy of digital complete-arch implant impressions with prefabricated aids using three intraoral scanners (IOSs) and explore the correlation between virtual deviation measurement and physical framework misfit. MATERIALS AND METHODS: Four edentulous maxillary master models with four and six parallel and angular implants were fabricated and scanned by a laboratory scanner as reference scans. Ten scans of each master model were acquired using three IOSs (IOS-T, IOS-M, and IOS-A) with and without prefabricated aids. Trueness and precision of root mean square (RMS) errors were measured. Ten aluminum alloy frameworks were fabricated, and the misfit was measured with a micro-computed tomography scan with one screw tightened. RESULTS: Trueness and precision showed significant improvement when prefabricated aids were used for all three IOSs (p < 0.010). Median (interquartile range) RMS errors of trueness reduced from 67.5 (30.4) to 61.8 (30.3) µm, from 100.6 (35.4) to 45.9 (15.1) µm, and from 52.7 (33.2) to 41.1 (22.5) µm for scanner IOS-T, IOS-M, and IOS-A, respectively (p < 0.010). The precision of IOS-A and IOS-M was significantly better than IOS-T when using prefabricated aid (p < 0.001). RMS errors and the maximum marginal misfit of the framework were significantly correlated (p < 0.001, R2 = 0.845). CONCLUSIONS: With the prefabricated aids, the accuracy of IOSs enhanced significantly in digital complete-arch implant impressions. Three IOSs showed different levels of improvement in accuracy. Virtual RMS errors <62.2 µm could be the clinically acceptable threshold (150 µm) for framework passive fit.

Accuracy of robotic surgery for dental implant placement: A systematic review and meta-analysis.

OBJECTIVES: To systematically analyze the accuracy of robotic surgery for dental implant placement. MATERIALS AND METHODS: PubMed, Embase, and Cochrane CENTRAL were searched on October 25, 2023. Model studies or clinical studies reporting the accuracy of robotic surgery for dental implant placement among patients with missing or hopeless teeth were included. Risks of bias in clinical studies were assessed. Meta-analyses were undertaken. RESULTS: Data from 8 clinical studies reporting on 109 patients and 242 implants and 13 preclinical studies were included. Positional accuracy was measured by comparing the implant plan in presurgery CBCT and the actual implant position in postsurgery CBCT. For clinical studies, the pooled (95% confidence interval) platform deviation, apex deviation, and angular deviation were 0.68 (0.57, 0.79) mm, 0.67 (0.58, 0.75) mm, and 1.69 (1.25, 2.12)°, respectively. There was no statistically significant difference between the accuracy of implants placed in partially or fully edentulous patients. For model studies, the pooled platform deviation, apex deviation, and angular deviation were 0.72 (0.58, 0.86) mm, 0.90 (0.74, 1.06) mm, and 1.46 (1.22, 1.70)°, respectively. No adverse event was reported. CONCLUSION: Within the limitation of the present systematic review, robotic surgery for dental implant placement showed suitable implant positional accuracy and had no reported obvious harm. Both robotic systems and clinical studies on robotic surgery for dental implant placement should be further developed.

A novel surgical approach using the "lateral corridor" for minimally invasive oblique lumbar interbody fusion at L5-S1: a clinical series and technical note.

PURPOSE: The minimally invasive oblique lumbar interbody fusion (MI-OLIF) L5-S1 was introduced to overcome the limitations of conventional fusion techniques, however, MI-OLIF is not possible using the standard method due to vascular structures in some cases. We aimed to introduce the "lateral corridor" and report the details of the surgical technique with a clinical case series. METHODS: We utilized the lateral access route of the left common iliac vein and named it the "lateral corridor", to distinguish the technique from the standard technique (central corridor). The type and frequency of branch vessels that required additional manipulations were reviewed, and the frequency of intraoperative vascular injury was investigated. RESULTS: Among the 107 patients who underwent MI-OLIF L5-S1, 26 patients (24.3%) who received the "lateral corridor" technique were included. Branch vessel ligation was required in 42.3% of the patients. The types of branch vessels that required ligation were seven cases (26.9%) of the iliolumbar vein (ILV) and six cases (23.1%) of ascending lumbar vein (ALV). The ILV and ALV were ligated in two cases. None of the patients developed intraoperative vascular injuries. CONCLUSION: We introduced the "lateral corridor" as an alternative approach for MI-OLIF L5-S1, implemented it in 24.3% of the patient cohort, and reported favorable outcomes devoid of vascular complications. The "lateral corridor" necessitated ligation of the ILV or ALV in 42.3% of cases. The "lateral corridor" approach appears to be a promising surgical technique, offering feasibility even in instances where the vascular anatomy precludes the employment of the conventional approach.

Association between sarcopenia-related markers and cholelithiasis: A prospective and Mendelian randomization study.

Cholelithiasis is a common digestive disease that drives a myriad of adverse complications. The correlation between sarcopenia and various digestive disorders has been extensively researched, whereas its association with cholelithiasis remains unreported. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses and establish a quantitative score reflecting the impact of sarcopenia-related markers on cholelithiasis. The prospective study involved 448 627 participants from the UK Biobank. Cox proportional hazard models were employed to investigate the correlation between sarcopenia-related markers and cholelithiasis. To quantitatively assess cholelithiasis risk, the SARCHO score was derived from a multivariable Cox model. Bidirectional two-sample MR analysis was conducted to validate the causal association. A total of 16 738 individuals developed cholelithiasis during a median follow-up of 12 years. Hazard ratios (HRs) of cholelithiasis decreased stepwise over skeletal muscle index tertiles (highest tertile: reference; middle tertile: 1.23, p < .001; lowest tertile: 1.33, p < .001). The tertiles of grip strength showed a similar pattern. Individuals with slow walking pace had a higher risk of cholelithiasis compared to those with normal walking pace (HR 1.23; p < .001). Our SARCHO score better quantifies the risk of cholelithiasis. MR analysis showed a causal relationship between muscle mass and cholelithiasis (OR 0.81; p < .001). No causal effect of cholelithiasis on lean mass was observed. Prospective and MR analyses have consistently demonstrated an increased risk of cholelithiasis in individuals with decreased muscle mass. Additionally, SARCHO score further quantified the cholelithiasis occurrence risk. These findings provide compelling evidence for muscle strengthening in preventing cholelithiasis.

Assessment of the Performance of Ultrasonography for Detecting Myofascial Trigger Points.

Needle electromyogram (EMG) research has suggested that endplate noise (EPN) is a characteristic of myofascial trigger points (MTrPs). Although several studies have observed MTrPs through ultrasonography, whether they are hyperechoic or hypoechoic in ultrasound images is still controversial. Therefore, this study determined the echogenicity of MTrP ultrasonography. In stage 1, the MTrP of rat masseter muscle was identified through palpation and marked. Needle EMG was performed to detect the presence of EPN. When EPN was detected, ultrasound scans and indwelling needles were used to identify the nodule with a different grayscale relative to that of its surrounding tissue, and the echogenicity of the identified MTrP was determined. In stage 2, these steps were reversed. An ultrasound scan was performed to detect the nodule at the marked site, and an EMG needle was inserted into the nodule to detect EPN. There were 178 recordings in each stage, obtained from 45 rats. The stage 1 results indicate that the MTrPs in ultrasound images were hypoechoic with a 100% sensitivity of assessment. In stage 2, the accuracy and precision of MTrP detection through ultrasonography were 89.9% and 89.2%, respectively. The results indicate that ultrasonography produces highly accurate and precise MTrP detection results.

Ethnic differences in the prevalence of amyloid positivity and cognitive trajectories.

INTRODUCTION: We investigated the prevalence of amyloid beta (Aß) positivity (+) and cognitive trajectories in Koreans and non-Hispanic Whites (NHWs). METHODS: We included 5121 Koreans from multiple centers across South Korea and 929 NHWs from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants underwent Aß positron emission tomography and were categorized into cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia stages. Age, sex, education, and apolipoprotein E. genotype were adjusted using multivariable logistic regression and stabilized inverse probability of treatment weights based on the propensity scores to mitigate imbalances in these variables. RESULTS: The prevalence of Aß+ was lower in CU Koreans than in CU NHWs (adjusted odds ratio 0.60). Aß+ Koreans showed a faster cognitive decline than Aß+ NHWs in the CU (B = -0.314, p = .004) and MCI stages (B = -0.385, p < .001). DISCUSSION: Ethnic characteristics of Aß biomarkers should be considered in research and clinical application of Aß-targeted therapies in diverse populations. HIGHLIGHTS: Koreans have a lower prevalence of Aß positivity compared to NHWs in the CU stage. The effects of Alzheimer's risk factors on Aß positivity differ between Koreans and NHWs. Aß-positive (Aß+) Koreans show faster cognitive decline than Aß+ NHWs in the CU and MCI stages.

Assessing cognitive impairment and disability in older adults through the lens of whole brain white matter patterns.

INTRODUCTION: This study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults. METHODS: We conducted an in-depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter-subject variability (WM-ISV). RESULTS: The white matter pattern ensemble model, combining MRI and amyloid PET, demonstrated a significantly higher classification performance for cognitive impairment and disability. Participants with Alzheimer's disease (AD) exhibited higher WM-ISV than participants with subjective cognitive decline, mild cognitive impairment, and vascular dementia. Furthermore, WM-ISV correlated significantly with blood-based biomarkers (such as glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]), and cognitive function and disability scores. DISCUSSION: Our results suggest that white matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making and determining cognitive impairment and disability. HIGHLIGHTS: The ensemble model combined both magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) and demonstrated a significantly higher classification performance for cognitive impairment and disability. Alzheimer's disease (AD) revealed a notably higher heterogeneity compared to that in subjective cognitive decline, mild cognitive impairment, or vascular dementia. White matter inter-subject variability (WM-ISV) was significantly correlated with blood-based biomarkers (glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]) and with the polygenic risk score for AD. White matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making processes and determining cognitive impairment and disability.

Modulation of Breast Cancer Cell Apoptosis and Macrophage Polarization by Mistletoe Lectin in 2D and 3D Models.

Korean mistletoe (Viscum album L. var. coloratum) is renowned for its medicinal properties, including anti-cancer and immunoadjuvant effects. This study aimed to elucidate the mechanisms by which Korean mistletoe lectin (V. album L. var. coloratum agglutinin; VCA) modulates breast cancer cell apoptosis and macrophage polarization. The specific objectives were to (1) investigate the direct effects of VCA on MCF-7 breast cancer cells and THP-1-derived M1/M2 macrophages; (2) analyze the impact of VCA on the paracrine interactions between these cell types; and (3) compare the efficacy of VCA in 2D vs. 3D co-culture models to bridge the gap between in vitro and in vivo studies. We employed both 2D and 3D models, co-culturing human M1/M2 macrophages with human MCF-7 breast cancer cells in a Transwell system. Our research demonstrated that M1 and M2 macrophages significantly influenced the immune and apoptotic responses of breast cancer cells when exposed to VCA. M1 macrophages exhibited cytotoxic characteristics and enhanced VCA-induced apoptosis in both 2D and 3D co-culture models. Conversely, M2 macrophages initially displayed a protective effect by reducing apoptosis in breast cancer cells, but this protective effect was reversed upon exposure to VCA. Furthermore, our findings illustrate VCA's ability to modulate M1 and M2 polarization in breast cancer cells. Finally, the use of magnetic 3D cell cultures suggests their potential to yield results comparable to conventional 2D cultures, bridging the gap between in vitro and in vivo studies.

Accuracy of traditional open-tray impression, stereophotogrammetry, and intraoral scanning with prefabricated aids for implant-supported complete arch prostheses with different implant distributions: An in vitro study.

STATEMENT OF PROBLEM: Conventional impression techniques for complete arch implant-supported fixed dental prostheses (CIFDPs) are technique sensitive. Stereophotogrammetry (SPG) and intraoral scanning (IOS) may offer alternatives to conventional impression making. PURPOSE: The purpose of this in vitro study was to assess the accuracy and passive fit of IOS with prefabricated aids, SPG, and open tray impression (OI) for CIFDPs with different implant distributions. MATERIAL AND METHODS: Three definitive casts with 4 parallel implants (4-PARA), 4 inclined implants (4-INCL), and 6 parallel implants (6-PARA) were fabricated. Three recording techniques were tested: IOS with prefabricated aids, SPG, and OI. The best and the worst scans were selected to fabricate 18 milled aluminum alloy frameworks. The trueness and precision of distance deviation (∆td and ∆pd), angular deviation (∆tθand ∆pθ), root mean square errors (∆tRMS for ∆pRMS), and passive fit score of frameworks were recorded. Two-way ANOVA was applied. RESULTS: SPG showed the best trueness and precision (95%CI of ∆td/∆tθ/∆tRMS, 31 to 39 µm, 0.22 to 0.28 degrees, 20 to 23 µm; 95%CI of ∆pd/∆pθ/∆pRMS, 9 to 11 µm, 0.06 to 0.08 degrees, 8 to 10 µm), followed by OI (61 to 83 µm, 0.33 to 0.48 degrees, 28 to 48 µm; 66 to 81 µm, 0.29 to 0.38 degrees, 32 to 41 µm) and IOS (143 to 193 µm, 0.37 to 0.50 degrees, 81 to 96 µm; 89 to 111 µm, 0.27 to 0.31 degrees, 51 to 62 µm). Tilted implants were associated with increased distance deviation. Increased implant number was associated with improved recording precision. The passive fit of frameworks was negatively correlated with the RMS error, and the correlation coefficient was -0.65 (P=.003). CONCLUSIONS: SPG had the best accuracy. Implant distributions affected implant precision. The RMS error can be used to evaluate the passive fit of frameworks.