Mitochondrial transplantation attenuates lipopolysaccharide-induced acute respiratory distress syndrome.

BACKGROUND: The mitochondria are essential organelles not only providing cellular energy in the form of ATP, but also regulating the inflammatory response and the cell death program. Mitochondrial dysfunction has been associated with various human diseases, including metabolic syndromes as well as inflammatory and neurodegenerative diseases. Acute respiratory distress syndrome (ARDS) is an acute pulmonary disorder characterized by uncontrolled alveolar inflammation, apoptotic lung epithelial/endothelial cells, and pulmonary edema. Despite the high mortality of ARDS, an effective pharmacotherapy to treat this disease has not been established yet. Therefore, identifying a novel targeted therapy for ARDS is important. Recently, exogenous mitochondrial transplantation was reported to be beneficial for treating mitochondrial dysfunction. The current study aimed to investigate the therapeutic effect of mitochondrial transplantation on ARDS in vitro and in vivo. METHODS: Mitochondria were isolated from human stem cells. For in vitro efficacy of mitochondrial transplantation on the inflammation and cell death, murine alveolar macrophages MH-S and human pulmonary microvascular endothelial cells HPMECs were exposed to LPS, respectively. The ARDS mice model established by a single intratracheal instillation of LPS was used for in vivo efficacy of intravenously treated mitochondria. RESULTS: Our results showed that the mitochondria isolated from human stem cells exhibited an anti-inflammatory effect against alveolar macrophages and an anti-apoptotic effect against the alveolar epithelial cells. Furthermore, intravenous mitochondrial treatment was associated with the attenuation of lung injury in the LPS-induced ARDS mice. CONCLUSION: Dual effects of mitochondria on anti-inflammation and anti-apoptosis support the potential of mitochondrial transplantation as a novel therapeutic strategy for ARDS.

Targeted and non-targeted identification of dye and chemical contaminants in Loji River, Indonesia using FT-ICR-MS.

This study utilized liquid chromatography (LC) alongside Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to explore the dyes and chemical contaminants in Loji River, Indonesia. We tentatively identified a total of 655 contaminants at various confidence level, subsequently classifying them into 22 distinct categories. Of the 54 dyes we detected, 12 corresponded with entries in our specialized in-house database. These 12 dyes were further confirmed by reference standards, matching both retention time (RT) and MS/MS spectra. LC-FT-ICR MS data showed that dyes from printing batik and textile industries are key contributors to river pollution. Particularly noteworthy were two sample locations that displayed substantial contamination, predominantly from azoic and reactive dyes. Additionally, pharmaceuticals were identified as one of the most frequently occurring contaminants, underscoring the inadequacies in the area's sewage management. To corroborate these findings, we conducted physicochemical, phytotoxicity, and acute toxicity tests, all of which verified the harmful effects of the Loji River's water on both the local flora and human populations. Notably, water samples that tested positive for dye contamination exhibited elevated toxicity levels. To the best of our knowledge, this study is pioneering in its molecular-level investigation of dye contamination in Southeast Asian rivers. Our results accentuate the pressing need for both targeted and non-targeted screening methods to identify contaminants in the surface waters of developing nations.

Optimal measurement method for anterior instability on stress radiographs in anterior cruciate ligament tear: Considering the effect of static anterior tibial subluxation.

INTRODUCTION: Accurate assessment of anterior cruciate ligament (ACL) function is vital for guiding treatment. Nevertheless, the presence of tibial subluxation in the neutral position of a patient with an ACL injury may potentially introduce a confounding factor. This study aims to investigate whether tibial subluxation in the neutral position affects the diagnosis of anterior instability in patients with ACL injuries, potentially impacting the reliability and diagnostic accuracy of stress radiography. METHODS: This study included 88 patients: 30 with acute complete ACL tears (acute group), 28 with chronic complete ACL tears (chronic group), and 30 patients who underwent knee arthroscopic surgery other than ACL reconstruction (control group). Side-to-side differences (SSD) in stress radiography were measured using the Telos load status and the SSD of the gap between the Telos load and unload statuses. Diagnostic accuracy of the two methods was assessed using areas under the receiver operating characteristic curves (AUCs). RESULTS: The load SSD (5.92 ± 5.28 mm) was higher than the load-unload SSD (4.27 ± 5.99 mm) in the chronic group (P = 0.017). The load SSD demonstrated a significantly higher diagnostic value than that of the load-unload SSD in the combined group (AUC = 0.920 vs. 0.830; P = 0.012) and chronic group (AUC = 0.913 vs. 0.754; P = 0.002). After adjusting the symptoms for radiographic duration from 6 to 3 months in the chronic group, the load SSD exhibited a significantly higher diagnostic value (AUC = 0.902) than that of the load-unload SSD (AUC = 0.740; P < 0.001). CONCLUSION: The load SSD provides superior diagnostic accuracy compared to the load-unload SSD in ACL tear cases, where static anterior tibial subluxation may result in false negatives. Although load-unload SSD may have diagnostic value within the first 3 months post-injury, the load SSD method provides a reliable assessment of ACL function for patients beyond this timeframe.

Transcranial direct current stimulation and neuronal functional connectivity in MCI: role of individual factors associated to AD.

Background: Alzheimer's disease (AD) encompasses a spectrum that may progress from mild cognitive impairment (MCI) to full dementia, characterized by amyloid-beta and tau accumulation. Transcranial direct current stimulation (tDCS) is being investigated as a therapeutic option, but its efficacy in relation to individual genetic and biological risk factors remains underexplored. Objective: To evaluate the effects of a two-week anodal tDCS regimen on the left dorsolateral prefrontal cortex, focusing on functional connectivity changes in neural networks in MCI patients resulting from various possible underlying disorders, considering individual factors associated to AD such as amyloid-beta deposition, APOE ϵ4 allele, BDNF Val66Met polymorphism, and sex. Methods: In a single-arm prospective study, 63 patients with MCI, including both amyloid-PET positive and negative cases, received 10 sessions of tDCS. We assessed intra- and inter-network functional connectivity (FC) using fMRI and analyzed interactions between tDCS effects and individual factors associated to AD. Results: tDCS significantly enhanced intra-network FC within the Salience Network (SN) and inter-network FC between the Central Executive Network and SN, predominantly in APOE ϵ4 carriers. We also observed significant sex*tDCS interactions that benefited inter-network FC among females. Furthermore, the effects of multiple modifiers, particularly the interaction of the BDNF Val66Met polymorphism and sex, were evident, as demonstrated by increased intra-network FC of the SN in female Met non-carriers. Lastly, the effects of tDCS on FC did not differ between the group of 26 MCI patients with cerebral amyloid-beta deposition detected by flutemetamol PET and the group of 37 MCI patients without cerebral amyloid-beta deposition. Conclusions: The study highlights the importance of precision medicine in tDCS applications for MCI, suggesting that individual genetic and biological profiles significantly influence therapeutic outcomes. Tailoring interventions based on these profiles may optimize treatment efficacy in early stages of AD.

Impact of multiple infections on risk of incident dementia according to subjective cognitive decline status: a nationwide population-based cohort study.

Background: The interrelation between infections, subjective cognitive decline (SCD), and dementia development is recognized, but not fully understood. This study explored the combined effect of specific infections and SCD on the risk of dementia. Objectives: To assess the influence of Helicobacter pylori, herpes simplex virus, varicella-zoster virus, and human papillomavirus on dementia risk in individuals with varying cognitive statuses, especially focusing on those with and without SCD. Methods: A cohort of 1,100,540 participants aged 66 years from the Korean National Health Insurance Service was divided into cognitively preserved (CP, n = 825,405) and SCD (n = 275,135) groups. This study analyzed the effects of single, dual, and triple infections on the risk of overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD) using incidence rates and hazard ratios. Results: The SCD group consistently showed a doubled risk of dementia, particularly AD, regardless of the number of infections. In the initial data, both the presence and number of infections, especially in the CP group, were associated with an increased dementia incidence and risk; however, this correlation disappeared after adjusting for covariates, hinting at a possible protective effect. Conclusion: Our findings emphasize that, while SCD is a steadfast risk factor for dementia, the role of infections is layered, subject to various influences, and requires more comprehensive exploration to fully understand their impact on dementia development.

Bilaterally positive head-impulse tests can differentiate AICA infarction from labyrinthitis.

Introduction: Video head-impulse tests (video-HITs) often fail to detect anterior inferior cerebellar artery (AICA) infarction due to peripheral and central vestibular system involvement. Anecdotal studies suggest that video-HITs may reveal bilateral impairment in AICA infarction. However, the diagnostic utility of video-HITs has not been established, particularly when compared to labyrinthitis, which accounts for the majority of acute audiovestibular syndrome (AAVS) cases. Methods: We reviewed the medical records of consecutive patients presenting with new-onset acute hearing loss and spontaneous vertigo (i.e., AAVS) between March 2018 and July 2023 at a tertiary hospital in South Korea. Video-HIT patterns were categorized as follows: (1) ipsilaterally positive, (2) contralaterally positive, (3) bilaterally normal, and (4) bilaterally positive. Results: Twenty-eight patients with AICA infarction (mean age ± standard deviation = 67 ± 15 years; 14 men) and 51 with labyrinthitis (63 ± 17 years, 26 men) were included in the analyses. Among the 28 patients with AICA infarction, 15 presented with AAVS in isolation, without other co-morbid neurologic deficits (15/28, 54%). The vestibulo-ocular reflex (VOR) gains of ipsilesional horizontal canals (HCs) ranged from 0.21 to 1.22 (median = 0.81, interquartile range [IQR] = 0.50-0.89). However, those for contralateral HC gain ranged from 0.57 to 1.19 (median = 0.89 [IQR = 0.73-0.97]). Collectively, HITs were bilaterally positive in 13 patients (including 12 patients with bilaterally positive HITs for the horizontal canal), normal in eight, ipsilesionally positive in six, and contralesionally positive in one patient with AICA infarction. The VOR gains were typically decreased ipsilaterally in 28 (28/51, 55%), normal in 17 (17/51, 33%), and decreased bilaterally in six patients with labyrinthitis (6/51, 12%). Logistic regression analysis revealed that bilaterally positive HITs (p = 0.004) and multiple vascular risk factors (p = 0.043) were more frequently associated with AICA infarction than labyrinthitis. Discussion: Among patients presenting with AAVS, bilaterally positive HITs can be indicative of AICA infarction in patients with multiple vascular risk factors.

Tailoring a CRISPR/Cas-based Epigenome Editor for Programmable Chromatin Acylation and Decreased Cytotoxicity.

Engineering histone acylation states can inform mechanistic epigenetics and catalyze therapeutic epigenome editing opportunities. Here, we developed engineered lysine acyltransferases that enable the programmable deposition of acetylation and longer-chain acylations. We show that targeting an engineered lysine crotonyltransferase results in weak levels of endogenous enhancer activation yet retains potency when targeted to promoters. We further identify a single mutation within the catalytic core of human p300 that preserves enzymatic activity while substantially reducing cytotoxicity, enabling improved viral delivery. We leveraged these capabilities to perform single-cell CRISPR activation screening and map enhancers to the genes they regulate in situ. We also discover acylation-specific interactions and find that recruitment of p300, regardless of catalytic activity, to prime editing sites can improve editing efficiency. These new programmable epigenome editing tools and insights expand our ability to understand the mechanistic role of lysine acylation in epigenetic and cellular processes and perform functional genomic screens.

Comparative life cycle assessment of natural and recycled aggregate concrete: A review.

Recycled aggregate concrete (RAC), mainly made from recycled materials such as construction and demolition waste (CDW), has emerged as a sustainable alternative to natural aggregate concrete (NAC). While RAC offers potential benefits in waste reduction and resource conservation, a comprehensive understanding of its environmental impact and sustainability compared to NAC has been lacking. This study addresses this gap by conducting a thorough review and analysis of comparative Life Cycle Assessment (LCA) studies between RAC and NAC. This paper synthesizes current literature to evaluate the environmental impact of both materials throughout their life cycles, from raw material extraction to disposal. It examines key factors such as energy consumption, greenhouse gas emissions, and resource depletion to provide a thorough comprehension of the effects on the environment of each concrete type throughout their life cycles. Challenges in using RAC as a sustainable concrete option, such as sourcing and quality control, are also discussed, along with recommendations for future research and industry practices. The findings indicate that the environmental impact of RAC compared to NAC is significantly influenced by transport distances and modes. In addition, the choice of functional units in LCAs substantially affects the comparison between RAC and NAC, with strength reliability offering a clear benefit by addressing concrete property variability and better reflecting real-world conditions.

The optimal measurement method considering reliability and validity in the anterior knee laxity of anterior cruciate ligament tears.

INTRODUCTION: To seek an optimal measurement method with high reliability and high validity for evaluation of the anterior knee laxity on stress radiographs and comparing the translation values to those of KT-2000 arthrometer. METHODS: Anterior knee laxity in 77 patients was measured preoperatively using the TelosTM and the KT-2000 arthrometer. Side-to-side difference measurements were taken using three conventional measuring methods and one proposed method (Modified Lateral). The knee position on the stress radiograph was evaluated and scored based on the stress radiograph qualifying criteria depending on stress film correctiveness. Intraclass correlation coefficients were analyzed to evaluate the reliability of the measurement methods and were compared between high (Group H) and low (Group L) radiograph quality score groups for each method. Validity was assessed by comparing the KT-2000 and the TelosTM using Pearson correlation (r value). RESULTS: The Modified Lateral method showed the best Intraclass Correlation Coefficients (ICCs), followed by Center to Center, and Medial to Medial and Lateral to Lateral methods without considering the quality of Telos. In the comparison between groups based on Telos quality for intra-rater reliability, the Medial to Medial (MM) method demonstrated the best reliability in both groups (MM: ICCs, Group H = 0.942, Group L = 0.917, P = 0.693). As for inter-rater reliability, the Modified Lateral (ML) method exhibited the best reliability in both groups (ML: ICCs, Group H = 0.923, Group L = 0.882, P = 0.547). The value measured using the ML method in Telos showed the highest correlation coefficient with the KT-2000 measured value in both groups H and L. There were no statistically significant differences among the correlation coefficient values. CONCLUSION: The Modified Lateral method is recommended for its high reliability, taking into account the differences in bilateral knee positions and anatomical discriminability on stress radiographs when evaluating anterior knee translation with Telos. It also best reflected the KT-2000 arthrometer. LEVEL OF EVIDENCE: Case Series, Level IV.

Glycoscience data content in the NCBI Glycans and PubChem.

Studying glycans and their functions in the body aids in the understanding of disease mechanisms and developing new treatments. This necessitates resources that provide comprehensive glycan data integrated with relevant information from other scientific fields such as genomics, genetics, proteomics, metabolomics, and chemistry. The present paper describes two resources at the U.S. National Center for Biotechnology Information (NCBI), the NCBI Glycans and PubChem, which provide glycan-related information useful for the glycoscience research community. The NCBI Glycans ( https://www.ncbi.nlm.nih.gov/glycans/ ) is a dedicated website for glycobiology data content at NCBI and provides quick access to glycan-related information scattered across multiple NCBI databases as well as other information resources external to NCBI. Importantly, the NCBI Glycans hosts the official web page for the symbol nomenclature for glycans (SNFG), which is the standard graphical representation of glycan structures recommended for scientific publication. On the other hand, PubChem ( https://pubchem.ncbi.nlm.nih.gov ) is a research-focused, large-scale public chemical database, containing a substantial number of glycan-containing records and is integrated with important glycoscience resources like GlyTouCan, GlyCosmos, and GlyGen. PubChem organizes glycan-related information within multiple data collections (i.e., Substance, Compound, Protein, Gene, Pathway, and Taxonomy) and provides various tools and services that allow users to access them both interactively through a web browser and programmatically through a REST-ful interface, including PUG-View. The NCBI Glycans and PubChem highlight glycan-related data and improve their accessibility, helping scientists exploit these data in their research.

Impact of Helicobacter pylori eradication on age-specific risk of incident dementia in patients with peptic ulcer disease: a nationwide population-based cohort study.

The impact of peptic ulcer disease (PUD) and Helicobacter pylori (H. pylori) eradication therapy on dementia risk in high H. pylori prevalence populations remains uncertain. This study investigates the relationship between PUD, H. pylori eradication, and dementia risk, including Alzheimer's disease (AD), in an elderly South Korean cohort, considering age and eradication timing. Data from the Korean National Health Insurance Service (2002-2015) for individuals aged 55-79 were analyzed. Participants were divided based on PUD and H. pylori therapy status. Propensity score matching was used to evaluate dementia incidence and hazard ratios over 5 and 10 years, alongside the timing of eradication therapy. PUD is linked to higher dementia risk at 5 and 10 years, more for overall dementia than AD, with eradication status not significantly altering the risk. Age-specific analysis showed increased AD risk in the 60s and 70s age groups. Late eradication therapy is correlated with a higher dementia risk. PUD is a risk factor for dementia in elderly South Koreans, particularly with delayed H. pylori therapy. The findings emphasize timely H. pylori management and its potential role in neurodegenerative disease prevention.

Effects of transcranial direct current stimulation on cognition in MCI with Alzheimer's disease risk factors using Bayesian analysis.

Despite the growing interest in precision medicine-based therapies for Alzheimer's disease (AD), little research has been conducted on how individual AD risk factors influence changes in cognitive function following transcranial direct current stimulation (tDCS). This study evaluates the cognitive effects of sequential tDCS on 63 mild cognitive impairment (MCI) patients, considering AD risk factors such as amyloid-beta deposition, APOE ε4, BDNF polymorphism, and sex. Using both frequentist and Bayesian methods, we assessed the interaction of tDCS with these risk factors on cognitive performance. Notably, we found that amyloid-beta deposition significantly interacted with tDCS in improving executive function, specifically Stroop Word-Color scores, with strong Bayesian support for this finding. Memory enhancements were differentially influenced by BDNF Met carrier status. However, sex and APOE ε4 status did not show significant effects. Our results highlight the importance of individual AD risk factors in modulating cognitive outcomes from tDCS, suggesting that precision medicine may offer more effective tDCS treatments tailored to individual risk profiles in early AD stages.

Machine Learning-Based Predictive Models for Early Detection of Cardiovascular Diseases: A Study Utilizing Patient Samples from a Tertiary Health Promotion Center in Korea.

A machine learning model was developed for cardiovascular diseases prediction based on 21,118 patient checkups data from a tertiary medical institution in Seoul, Korea, collected between 2009 and 2021. XGBoost algorithm showed the highest predictive performance, with an average AUROC of 0.877. In survival analysis, XGBSE achieved an AUROC exceeding 0.9 for 2-9 year predictions, with a C-index of 0.878 across all diseases, outperforming Cox regression (C-index of 0.887). A high-performance prediction model for cardiovascular diseases using the XGBSE algorithm was successfully developed and is poised for real-world clinical application following external simplification and validation.

Pycnogenol-Assisted Alleviation of Titanium Dioxide Nanoparticle-Induced Lung Inflammation via Thioredoxin-Interacting Protein Downregulation.

Titanium dioxide nanoparticles (TiO2NPs) are used in products that are applied to the human body, such as cosmetics and food, but their biocompatibility remains controversial. Pycnogenol (PYC), a natural extract of pine bark, exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether PYC effectively alleviates pulmonary toxicity induced by airway exposure to TiO2NPs, and the beneficial effects of PYC were explained through the analysis of changes to the mechanism of cytotoxicity. TiO2NPs induced pulmonary inflammation and mucus production, increased the levels of malondialdehyde, and upregulated thioredoxin-interacting protein (TXNIP) and cleaved-caspase 3 (Cas3) in the lungs of mice. However, PYC treatment reduced the levels of all toxicity markers of TiO2NPs and restored glutathione levels. These antioxidant and anti-inflammatory effects of PYC were also demonstrated in TiO2NP-exposed human airway epithelial cells by increasing the mRNA levels of antioxidant enzymes and decreasing the expression of TXNIP, cleaved-Cas3, and inflammatory mediators. Taken together, our results showed that PYC attenuated TiO2NP-induced lung injury via TXNIP downregulation. Therefore, our results suggest the potential of PYC as an effective anti-inflammatory and antioxidant agent against TiO2NP-induced pulmonary toxicity.

The prognostic impact of psychiatric intervention on alcohol-associated liver disease : the UK Biobank cohort study.

Background/Aims: Alcohol-associated liver disease (ALD) is a public health concern. ALD patients often have psychiatric comorbidities, but the effects of psychiatric interventions on ALD are not well-established. This study explores the prognostic impact of psychiatric intervention on ALD within UK Biobank cohort. Methods: This population-based study included 2,417 ALD patients from the UK Biobank cohort. Psychiatric intervention was defined by a consultation with psychiatrists during hospitalization or a history of medication related to alcohol use disorder and psychiatric comorbidities. Survival analysis was conducted, incorporating propensity score matching (PSM), to precisely assess the impact of psychiatric intervention. Results: Among 2,417 ALD patients, those with F10 (mental disorders due to alcohol) codes had poorer survival outcomes. Psychiatric intervention significantly improved the outcomes of both all-cause and liver-related mortality and reduced the incidence of liver cirrhosis. In subgroup or 2-year landmark analyses, psychiatric intervention consistently showed a survival benefit in ALD patients. In the multivariate analysis, psychiatric intervention was identified as a favorable prognostic factor (hazard ratio, 0.780; P = 0.002 after PSM). Conclusions: This study demonstrates the favorable effect of psychiatric intervention in ALD patients with psychiatric comorbidities. These findings emphasize the importance of integrated management for ALD patients to address both their medical and psychiatric aspects. Therefore, we suggest the potential benefits of early psychiatric interventions in improving survival outcomes in ALD.

Recording and Revealing 2.5D Nanopatterned Hidden Information on Silk Protein Bioresists.

Nanopatterning on biomaterials has attracted significant attention as it can lead to the development of biomedical devices capable of performing diagnostic and therapeutic functions while being biocompatible. Among various nanopatterning techniques, electron-beam lithography (EBL) enables precise and versatile nanopatterning in desired shapes. Various biomaterials are successfully nanopatterned as bioresists by using EBL. However, the use of high-energy electron beams (e-beams) for high-resolutive patterning has incorporated functional materials and has caused adverse effects on biomaterials. Moreover, the scattering of electrons not absorbed by the bioresist leads to proximity effects, thus deteriorating pattern quality. Herein, EBL-based nanopatterning is reported by inducing molecular degradation of amorphous silk fibroin, followed by selectively inducing secondary structures. High-resolution EBL nanopatterning is achievable, even at low-energy e-beam (5 keV) and low doses, as it minimizes the proximity effect and enables precise 2.5D nanopatterning via grayscale lithography. Additionally, integrating nanophotonic structures into fluorescent material-containing silk allows for fluorescence amplification. Furthermore, this post-exposure cross-linking way indicates that the silk bioresist can maintain nanopatterned information stored in silk molecules in the amorphous state, utilizing for the secure storage of nanopatterned information as a security patch. Based on the fabrication technique, versatile biomaterial-based nanodevices for biomedical applications can be envisioned.

Sequential Comparison of Knee Muscle Strength after Anterior Cruciate Ligament Reconstruction between Hamstring Autograft and Tibialis Anterior Allograft: Propensity Score Matched Pair Analysis.

Among the graft options for anterior cruciate ligament reconstruction (ACLR), hamstring autografts are widely regarded as the preferred choice for primary ACLR among orthopedic surgeons worldwide. However, concerns persist regarding postoperative knee flexor weakness. We aimed to compare knee extensor and flexor strengths between hamstring autograft and tibialis anterior allograft groups in ACLR patients, who were propensity score-matched based on baseline characteristics. A retrospective analysis included 58 matched pairs who underwent isokinetic strength tests at 6 and 12 months post operation. Isokinetic muscle strength tests found no significant difference in knee extensor and flexor strength at 6 months post operation between the hamstring autograft and tibial anterior allograft groups. At 12 months, the hamstring autograft group exhibited significantly greater knee flexor deficit (total work and average power) compared to the allograft group, despite no differences in extensor strength or patient-reported outcomes. This study highlights the impact of hamstring autograft harvesting on muscle strength and recovery following ACLR in short-term period.

A Comparative Analysis of Two Automated Quantification Methods for Regional Cerebral Amyloid Retention: PET-Only and PET-and-MRI-Based Methods.

Accurate quantification of amyloid positron emission tomography (PET) is essential for early detection of and intervention in Alzheimer's disease (AD) but there is still a lack of studies comparing the performance of various automated methods. This study compared the PET-only method and PET-and-MRI-based method with a pre-trained deep learning segmentation model. A large sample of 1180 participants in the Catholic Aging Brain Imaging (CABI) database was analyzed to calculate the regional standardized uptake value ratio (SUVR) using both methods. The logistic regression models were employed to assess the discriminability of amyloid-positive and negative groups through 10-fold cross-validation and area under the receiver operating characteristics (AUROC) metrics. The two methods showed a high correlation in calculating SUVRs but the PET-MRI method, incorporating MRI data for anatomical accuracy, demonstrated superior performance in predicting amyloid-positivity. The parietal, frontal, and cingulate importantly contributed to the prediction. The PET-MRI method with a pre-trained deep learning model approach provides an efficient and precise method for earlier diagnosis and intervention in the AD continuum.

Combined Anterolateral Ligament Reconstruction Results in Better Knee Stability and More Satisfactory Subjective Outcomes in Non-Athlete Patients Undergoing Revision Anterior Cruciate Ligament Reconstruction.

Background: Consensus has not yet been reached regarding combined anterior cruciate ligament reconstruction (ALLR) with revisional anterior cruciate ligament reconstruction (RACLR). We aimed to compare the clinical outcomes between patients who underwent isolated RACLR and those who underwent RACLR combined with ALLR. Methods: Between June 2010 and June 2021, 49 patients who underwent RACLR were retrospectively reviewed over a 24-month follow-up. Patients were categorized into the isolated RACLR (n = 37, group 1) or combined ALLR group (n = 12, group 2). Clinical outcomes were evaluated with several patient-reported outcome measures (PROMs) and minimal clinically important differences (MCIDs) for each PROM. The side-to-side difference (SSD) of the anterior instability was measured. The pivot-shift test was performed. Results: Baseline characteristics showed no differences between the groups. PROMs showed no significant differences between the groups at the 2-year follow-up. Group 2 was superior to group 1 in the MCID achievement rate for Lysholm knee and International Knee Documentation Committee (IKDC) subjective scores at 24 months postoperatively. At the final follow-up, the proportion of IKDC grade A in SSD for anterior laxity was higher in group 2 than in group 1 (58.3% versus [vs.] 18.3%, p = 0.009), and the proportion of pivot-shift grade 0 was also higher in group 2 (66.7% vs. 27.0%, p = 0.013). The "near return to activity" rate was also higher in group 2 than in group 1 (83.3% vs. 45.9%, p = 0.043). Conclusions: Combining ALLR with RACLR in non-athletes results in a higher proportion of patients with less mechanical graft failure and satisfactory clinical outcomes.

Ultrathin silk nanofiber-carbon nanotube skin tattoos for wirelessly triggered and temperature feedbacked transdermal drug delivery.

Transdermal drug delivery has emerged as an alternative to conventional drug delivery systems as it enables painless and convenient drug administration. However, next-generation healthcare systems need to facilitate "on-demand" delivery operations and should be highly efficient to penetrate the physiological barriers in the skin. Here, we report an ultrathin dye-loaded epidermal tattoo (UDET) that allows wirelessly stimulated drug delivery with high efficiency. The UDET consists of an electrospun dye-loaded silk nanofiber mat and a covered carbon nanotube (CNT) layer. UDETs are conformally tattooed on pigskins and show stable operation under mechanical deformation. Biological fluorescence dyes such as vitamin B12, riboflavin, rhodamine B, and sodium fluorescein are applied as model drugs. Illuminating the UDET by a low-power light-emitting diode (< 34.5 mW/cm2) triggers transdermal drug delivery due to heat generation. The CNTs convert the absorbed light into heat, and then the dyes loaded on silk can be diffused through the epidermis. The CNT layer is electrically conductive and can detect the temperature by reading the resistance change (0.1917 Ω/°C). This indicates that the UDET can be used simultaneously to read temperature and deliver the loaded dye molecules, making it a promising on-demand drug delivery strategy for future medicine technology. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00363-6.