Supervised contrastive learning enhances graph convolutional networks for predicting neurodevelopmental deficits in very preterm infants using brain structural connectome.

Very preterm (VPT) infants (born at less than 32 weeks gestational age) are at high risk for various adverse neurodevelopmental deficits. Unfortunately, most of these deficits cannot be accurately diagnosed until the age of 2-5 years old. Given the benefits of early interventions, accurate diagnosis and prediction soon after birth are urgently needed for VPT infants. Previous studies have applied deep learning models to learn the brain structural connectome (SC) to predict neurodevelopmental deficits in the preterm population. However, none of these models are specifically designed for graph-structured data, and thus may potentially miss certain topological information conveyed in the brain SC. In this study, we aim to develop deep learning models to learn the SC acquired at term-equivalent age for early prediction of neurodevelopmental deficits at 2 years corrected age in VPT infants. We directly treated the brain SC as a graph, and applied graph convolutional network (GCN) models to capture complex topological information of the SC. In addition, we applied the supervised contrastive learning (SCL) technique to mitigate the effects of the data scarcity problem, and enable robust training of GCN models. We hypothesize that SCL will enhance GCN models for early prediction of neurodevelopmental deficits in VPT infants using the SC. We used a regional prospective cohort of ∼280 VPT infants who underwent MRI examinations at term-equivalent age from the Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS). These VPT infants completed neurodevelopmental assessment at 2 years corrected age to evaluate cognition, language, and motor skills. Using the SCL technique, the GCN model achieved mean areas under the receiver operating characteristic curve (AUCs) in the range of 0.72∼0.75 for predicting three neurodevelopmental deficits, outperforming several competing models. Our results support our hypothesis that the SCL technique is able to enhance the GCN model in our prediction tasks.

Self-Catalyzed Hydrogenated Carbon Nano-Onions Facilitates Mild Synthesis of Transparent Nano-Polycrystalline Diamond.

Transparent nano-polycrystalline diamond (t-NPD) possesses superior mechanical properties compared to single and traditional polycrystalline diamonds. However, the harsh synthetic conditions significantly limit its synthesis and applications. In this study, a synthesis routine is presented for t-NPD under low pressure and low temperature conditions, 10 GPa, 1600 °C and 15 GPa, 1350 °C similar with the synthesis condition of organic precursor. Self-catalyzed hydrogenated carbon nano-onions (HCNOs) from the combustion of naphthalene enable synthesis under nearly industrial conditions, which are like organic precursor and much lower than that of graphite and other carbon allotropes. This is made possible thanks to the significant impact of hydrogen on the thermodynamics, as it chemically facilitates phase transition. Ubiquitous nanotwinned structures are observed throughout t-NPD due to the high concentration of puckered layers and stacking faults of HCNOs, which impart a Vickers hardness about 140 GPa. This high hardness and optical transparency can be attributed to the nanocrystalline grain size, thin intergranular films, absence of secondary phase and pore-free features. The facile and industrial-scale synthesis of the HCNOs precursor, and mild synthesis conditions make t-NPD suitable for a wide range of potential applications.

HIV-1 mRNA knockdown with CRISPR/CAS9 enhances neurocognitive function.

Mixed glia are infiltrated with HIV-1 virus early in the course of infection leading to the development of a persistent viral reservoir in the central nervous system. Modification of the HIV-1 genome using gene editing techniques, including CRISPR/Cas9, has shown great promise towards eliminating HIV-1 viral reservoirs; whether these techniques are capable of removing HIV-1 viral proteins from mixed glia, however, has not been systematically evaluated. Herein, the efficacy of adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing for eliminating HIV-1 messenger RNA (mRNA) from cortical mixed glia was evaluated in vitro and in vivo. In vitro, a within-subjects experimental design was utilized to treat mixed glia isolated from neonatal HIV-1 transgenic (Tg) rats with varying doses (0, 0.9, 1.8, 2.7, 3.6, 4.5, or 5.4 µL corresponding to a physical titer of 0, 4.23 × 109, 8.46 × 109, 1.269 × 1010, 1.692 × 1010, 2.115 × 1010, and 2.538 × 1010 gc/µL) of CRISPR/Cas9 for 72 h. Dose-dependent decreases in the number of HIV-1 mRNA, quantified using an innovative in situ hybridization technique, were observed in a subset (i.e., n = 5 out of 8) of primary mixed glia. In vivo, HIV-1 Tg rats were retro-orbitally inoculated with CRISPR/Cas9 for two weeks, whereby treatment resulted in profound excision (i.e., approximately 53.2%) of HIV-1 mRNA from the medial prefrontal cortex. Given incomplete excision of the HIV-1 viral genome, the clinical relevance of HIV-1 mRNA knockdown for eliminating neurocognitive impairments was evaluated via examination of temporal processing, a putative neurobehavioral mechanism underlying HIV-1-associated neurocognitive disorders (HAND). Indeed, treatment with CRISPR/Cas9 protractedly, albeit not permanently, restored the developmental trajectory of temporal processing. Proof-of-concept studies, therefore, support the susceptibility of mixed glia to gene editing and the potential of CRISPR/Cas9 to serve as a novel therapeutic strategy for HAND, even in the absence of full viral eradication.

Paenalcaligenes faecalis sp. nov., a novel species of the family Alcaligenaceae isolated from chicken faeces.

A Gram-negative, motile, rod-shaped aerobic and alkalogenic bacterium, designated as strain YLCF04T, was isolated from chicken faeces. Its growth was optimal at 28 °C (range, 10-40 °C), pH 8 (range, pH 6-9) and in 1 % (w/v) NaCl (range, 0-10 %). It was classified to the genus Paenalcaligenes and was most closely related to Paenalcaligenes hominis CCUG 53761AT (97.5 % similarity) based on 16S rRNA gene sequence analysis. Average nucleotide identity and digital DNA-DNA hybridization values between YLCF04T and P. hominis CCUG 53761AT were 76.3 and 18.2 %, respectively. Strain YLCF04T has a genome size of 2.7 Mb with DNA G+C content of 46.3 mol%. Based on its phylogenetic, genomic, phenotypic and biochemical characteristics, strain YLCF04T represents a novel species of the genus Paenalcaligenes, for which the name Paenalcaligenes faecalis sp. nov. is proposed. The type strain is YLCF04T (=CCTCC AB 2022359T= KCTC 92789T).

Machine Learning Diagnosis of Small-Bowel Crohn Disease Using T2-Weighted MRI Radiomic and Clinical Data.

BACKGROUND. Radiologists have variable diagnostic performance and considerable interreader variability when interpreting MR enterography (MRE) examinations for suspected Crohn disease (CD). OBJECTIVE. The purposes of this study were to develop a machine learning method for predicting ileal CD by use of radiomic features of ileal wall and mesenteric fat from noncontrast T2-weighted MRI and to compare the performance of the method with that of expert radiologists. METHODS. This single-institution study included retrospectively identified patients who underwent MRE for suspected ileal CD from January 1, 2020, to January 31, 2021, and prospectively enrolled participants (patients with newly diagnosed ileal CD or healthy control participants) from December 2018 to October 2021. Using axial T2-weighted SSFSE images, a radiologist selected two slices showing greatest terminal ileal wall thickening. Four ROIs were segmented, and radiomic features were extracted from each ROI. After feature selection, support-vector machine models were trained to classify the presence of ileal CD. Three fellowship-trained pediatric abdominal radiologists independently classified the presence of ileal CD on SSFSE images. The reference standard was clinical diagnosis of ileal CD based on endoscopy and biopsy results. Radiomic-only, clinical-only, and radiomic-clinical ensemble models were trained and evaluated by nested cross-validation. RESULTS. The study included 135 participants (67 female, 68 male; mean age, 15.2 ± 3.2 years); 70 were diagnosed with ileal CD. The three radiologists had accuracies of 83.7% (113/135), 88.1% (119/135), and 86.7% (117/135) for diagnosing CD; consensus accuracy was 88.1%. Interradiologist agreement was substantial (κ = 0.78). The best-performing ROI was bowel core (AUC, 0.95; accuracy, 89.6%); other ROIs had worse performance (whole-bowel AUC, 0.86; fat-core AUC, 0.70; whole-fat AUC, 0.73). For the clinical-only model, AUC was 0.85 and accuracy was 80.0%. The ensemble model combining bowel-core radiomic and clinical models had AUC of 0.98 and accuracy of 93.5%. The bowel-core radiomic-only model had significantly greater accuracy than radiologist 1 (p = .009) and radiologist 2 (p = .02) but not radiologist 3 (p > .99) or the radiologists in consensus (p = .05). The ensemble model had greater accuracy than the radiologists in consensus (p = .02). CONCLUSION. A radiomic machine learning model predicted CD diagnosis with better performance than two of three expert radiologists. Model performance improved when radiomic data were ensembled with clinical data. CLINICAL IMPACT. Deployment of a radiomic-based model including T2-weighted MRI data could decrease interradiologist variability and increase diagnostic accuracy for pediatric CD.

Deep-Learning Models for Abdominal CT Organ Segmentation in Children: Development and Validation in Internal and Heterogeneous Public Datasets.

Background: Deep-learning abdominal organ segmentation algorithms have shown excellent results in adults; validation in children is sparse. Objective: To develop and validate deep-learning models for liver, spleen, and pancreas segmentation on pediatric CT examinations. Methods: This retrospective study developed and validated deep-learning models for liver, spleen, and pancreas segmentation using 1731 CT examinations (1504 training, 221 testing), derived from three internal institutional pediatric (age ≤18) datasets (n=483) and three public datasets comprising pediatric and adult examinations with various pathologies (n=1248). Three deep-learning model architectures (SegResNet, DynUNet, and SwinUNETR) from the Medical Open Network for AI (MONAI) framework underwent training using native training (NT), relying solely on institutional datasets, and transfer learning (TL), incorporating pre-training on public datasets. For comparison, TotalSegmentator (TS), a publicly available segmentation model, was applied to test data without further training. Segmentation performance was evaluated using mean Dice similarity coefficient (DSC), with manual segmentations as reference. Results: For internal pediatric data, DSC for normal liver was 0.953 (TS), 0.964-0.965 (NT models), and 0.965-0.966 (TL models); normal spleen, 0.914 (TS), 0.942-0.945 (NT models), and 0.937-0.945 (TL models); normal pancreas, 0.733 (TS), 0.774-0.785 (NT models), and 0.775-0.786 (TL models); pancreas with pancreatitis, 0.703 (TS), 0.590-0.640 (NT models), and 0.667-0.711 (TL models). For public pediatric data, DSC for liver was 0.952 (TS), 0.876-0.908 (NT models), and 0.941-0.946 (TL models); spleen, 0.905 (TS), 0.771-0.827 (NT models), and 0.897-0.926 (TL models); pancreas, 0.700 (TS), 0.577-0.648 (NT models), and 0.693-0.736 (TL models). For public primarily adult data, DSC for liver was 0.991 (TS), 0.633-0.750 (NT models), and 0.926-0.952 (TL models); spleen, 0.983 (TS), 0.569-0.604 (NT models), and 0.923-0.947 (TL models); pancreas, 0.909 (TS), 0.148-0.241 (NT models), and 0.699-0.775 (TL models). DynUNet-TL was selected as the best-performing NT or TL model and was made available as an opensource MONAI bundle (https://github.com/cchmc-dll/pediatric_abdominal_segmentation_bundle.git). Conclusion: TL models trained on heterogeneous public datasets and fine-tuned using institutional pediatric data outperformed internal NT models and TotalSegmentator across internal and external pediatric test data. Segmentation performance was better in liver and spleen than in pancreas. Clinical Impact: The selected model may be used for various volumetry applications in pediatric imaging.

SPACA6P-AS: a trailblazer in breast cancer pathobiology and therapeutics.

OBJECTIVE: The primary objective of this investigation is to delve into the involvement of the long noncoding RNA (lncRNA) SPACA6P-AS in breast cancer (BC) development, focusing on its expression pattern, association with clinical-pathological features, impact on prognosis, as well as its molecular and immunological implications. METHODS: Bioinformatics analysis was conducted utilizing RNA sequencing data of 1083 BC patients from the TCGA database. Functional exploration of SPACA6P-AS was carried out through the construction of survival curves, GO and KEGG enrichment analysis, and single-sample gene set enrichment analysis (ssGSEA). Furthermore, its functionality was validated through in vitro cell experiments and in vivo nude mouse model experiments. RESULTS: SPACA6P-AS showed a remarkable increase in expression levels in BC tissues (p < 0.001) and demonstrated a close relationship to poor prognosis (overall survival HR = 1.616, progression-free interval HR = 1.40, disease-specific survival HR = 1.54). Enrichment analysis revealed that SPACA6P-AS could impact biological functions such as protease regulation, endopeptidase inhibitor activity, taste receptor activity, taste transduction, and maturity-onset diabetes of the young pathway. ssGSEA analysis indicated a negative correlation between SPACA6P-AS expression and immune cell infiltration like dendritic cells and neutrophils, while a positive correlation was observed with central memory T cells and T helper 2 cells. Results from in vitro and in vivo experiments illustrated that silencing SPACA6P-AS significantly inhibited the proliferation, migration, and invasion capabilities of BC cells. In vitro experiments also highlighted that dendritic cells with silenced SPACA6P-AS exhibited enhanced capabilities in promoting the proliferation of autologous CD3 + T cells and cytokine secretion. These discoveries elucidate the potential multifaceted roles of SPACA6P-AS in BC, including its potential involvement in modulating immune cell infiltration in the tumor microenvironment. CONCLUSION: The high expression of lncRNA SPACA6P-AS in BC is closely linked to poor prognosis and may facilitate tumor progression by influencing specific biological processes, signaling pathways, and the immune microenvironment. The regulatory role of SPACA6P-AS positions it as a prospective biomarker and target for therapeutic approaches for BC diagnosis and intervention.

Epidemiology of Vancomycin in Combination With Piperacillin/Tazobactam-Associated Acute Kidney Injury in Children: A Systematic Review and Meta-analysis.

BACKGROUND: Several studies have shown that vancomycin combined with piperacillin/tazobactam (VPT) increased the risk of acute kidney injury (AKI) compared with other antibiotics in children. However, the epidemiology of VPT-associated AKI in children is unknown. OBJECTIVE: To evaluate the incidence and risk factors of VPT-associated AKI in children. DATA SOURCES: Literature databases of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and China Biology Medicine Disc were searched from inception to November 2023. References of included studies were also manually checked. STUDY SELECTION AND DATA EXTRACTION: Two independent reviewers selected studies, extracted data, and quality assessment. Meta-analyses were performed to quantify the incidence and risk factors of VPT-associated AKI in children. DATA SYNTHESIS: Sixteen cohort studies were identified. Overall, the incidence of VPT-associated AKI in children was 24.3% (95% CI: 17.9%-30.6%). The incidence of VPT-associated AKI in critically ill children (26.6%) was higher than that in noncritically ill children (10.9%). Moreover, higher serum vancomycin trough concentration (>15 mg/L), use of vasopressors, combination of nephrotoxins and intensive care unit admission were risk factors for VPT-associated AKI in children (P < 0.05). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Identifying high-risk groups and determining safer treatments is critical to reducing the incidence of VPT-associated AKI in children. CONCLUSIONS: The incidence of VPT-associated AKI in children is high, especially in critically ill children. Medication regimens should be personalized based on the presence of individual risk factors. Moreover, renal function was regularly assessed throughout treatment with VPT.

Use of statins and risks of ovarian, uterine, and cervical diseases: a cohort study in the UK Biobank.

PURPOSE: To examine the associations between use of statins and risks of various ovarian, uterine, and cervical diseases, including ovarian cancer, endometrial cancer, cervical cancer, ovarian cyst, polycystic ovarian syndrome, endometriosis, endometrial hyperplasia, endometrial polyp, and cervical polyp. METHODS: We conducted a cohort study among female participants in the UK Biobank. Information on the use of statins was collected through verbal interview. Outcome information was obtained by linking to national cancer registry data and hospital inpatient data. We used Cox proportional hazards regression to examine the associations. RESULTS: A total of 180,855 female participants (18,403 statin users and 162,452 non-users) were included. Use of statins was significantly associated with increased risks of cervical cancer (adjusted hazard ratio (HR), 1.55; 95% confidence interval (95% CI), 1.05-2.30) and polycystic ovarian syndrome (adjusted HR, 4.39; 95% CI, 1.68-11.49). However, we observed no significant association between use of statins and risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial hyperplasia, endometrial polyp, or cervical polyp. CONCLUSION: Our findings suggest that use of statins is associated with increased risks of cervical cancer and polycystic ovarian syndrome, but is not associated with increased or decreased risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial polyp, or cervical polyp.

Structure-based design and synthesis of anti-fibrotic compounds derived from para-positioned 3,4,5-trisubstituted benzene.

Liver fibrosis is an abnormal wound-healing response to liver injuries. It can lead to liver cirrhosis, and even liver cancer and liver failure. There is a lack of treatment for liver fibrosis and it is of great importance to develop anti-fibrotic drugs. A pivotal event in the process of developing liver fibrosis is the activation of hepatic stellate cells (HSCs), in which the nuclear receptor Nur77 plays a crucial role. This study aimed to develop novel anti-fibrotic agents with Nur77 as the drug target by modifying the structure of THPN, a Nur77-binding and anti-melanoma compound. Specifically, a series of para-positioned 3,4,5-trisubstituted benzene ring compounds with long-chain backbone were generated and tested for anti-fibrotic activity. Among these compounds, compound A8 was with the most potent and Nur77-dependent inhibitory activity against TGF-ß1-induced activation of HSCs. In a crystal structure analysis, compound A8 bound Nur77 in a peg-in-hole mode as THPN did but adopted a different conformation that could interfere the Nur77 interaction with AKT, which was previous shown to be important for an anti-fibrotic activity. In a cell-based assay, compound A8 indeed impeded the interaction between Nur77 and AKT leading to the stabilization of Nur77 without the activation of AKT. In a mouse model, compound A8 effectively suppressed the activation of AKT signaling pathway and up-regulated the cellular level of Nur77 to attenuate the HSCs activation and ameliorate liver fibrosis with no significant toxic side effects. Collectively, this work demonstrated that Nur77-targeting compound A8 is a promising anti-fibrotic drug candidate.

Adverse drug reaction signal detection methods in spontaneous reporting system: A systematic review.

BACKGROUND: A series of signal detection methods have been developed to detect adverse drug reaction (ADR) signals in spontaneous reporting system. However, different signal detection methods yield quite different signal detection results, and we do not know which method has the best detection performance. How to choose the most suitable signal detection method is an urgent problem to be solved. In this study, we systematically reviewed the characteristics and application scopes of current signal detection methods, with the goal of providing references for the optimization selection of signal detection methods in spontaneous reporting system. METHODS: We searched six databases from inception to January 2023. The search strategy targeted literatures regarding signal detection methods in spontaneous reporting system. We used thematic analysis approach to summarize the advantages, disadvantages, and application scope of each signal detection method. RESULTS: A total of 93 literatures were included, including 27 reviews and 66 methodological studies. Moreover, 31 signal detection methods were identified in these literatures. Each signal detection method has its inherent advantages and disadvantages, resulting in different application scopes of these methods. CONCLUSION: Our systematic review finds that there are variabilities in the advantages, disadvantages, and application scopes of different signal detection methods. This finding indicates that the most suitable signal detection method varies across different drug safety scenarios. Moreover, when selecting signal detection method in a particular drug safety scenario, the following factors need to be considered: purpose of research, database size, drug characteristics, adverse event characteristics, and characteristics of the relations between drugs and adverse events.

Use of municipal solid waste incineration fly ash as a supplementary cementitious material: CO2 mineralization coupled with mechanochemical pretreatment.

The use of municipal solid waste incineration fly ash, commonly referred to as "fly ash", as a supplementary cementitious material (SCM), has been explored to mitigate the CO2 emissions resulting from cement production. Nevertheless, the incorporation of fly ash as an SCM in mortar has been shown to weaken its compressive strength and increase the risk of heavy metal leaching. In light of these challenges, this study aims to comprehensively evaluate the influence of CO2 pressure, temperature, and residual water/binder ratio on the CO2 uptake and compressive strength of mortar when combined with fly ash. Additionally, this study systematically examines the feasibility of mechanochemical pretreatment, which enhances the homogenization of fly ash and augments the density of the mortar's microstructure. The results indicate that the use of mechanochemical pretreatment leads to a notable 43.6% increase in 28-day compressive strength and diminishes the leaching of As, Ba, Ni, Pb, Se, and Zn by 17.9-77.8%. Finally, a reaction kinetics model is proposed to elucidate the CO2 sequestration process under varying conditions. These findings offer valuable guidance for incorporating fly ash as an SCM and CO2 sequestrator in mortar.

Sarcopenia is associated with leukopenia in urothelial carcinoma patients who receive tislelizumab combined with gemcitabine and cisplatin therapy.

BACKGROUND: In the era of combination therapy, there has been limited research on body composition. Specific body composition, such as sarcopenia, possesses the potential to serve as a predictive biomarker for toxic effects and clinical response in patients with urothelial carcinoma (UC) undergoing tislelizumab combined with gemcitabine and cisplatin (T + GC). MATERIALS AND METHODS: A total of 112 UC patients who received T + GC were selected at the Affiliated Hospital of Xuzhou Medical University from April 2020 to January 2023. Baseline patient characteristics and detailed hematological parameters were collected using the electronic medical system and laboratory examinations. The computed tomography images of patients were analyzed to calculate psoas muscle mass index (PMI). We evaluated the association between sarcopenia (PMI < 4.5 cm2/m2 in men; PMI < 3.3 cm2/m2 in women) and both hematological toxicity and tumor response. RESULTS: Overall, of the 112 patients (65.2% male, median age 56 years), 43 (38.4%) were defined as sarcopenia. Patients with sarcopenia were notably older (p = 0.037), more likely to have hypertension (p = 0.009), and had poorer ECOG-PS (p = 0.027). Patients with sarcopenia were more likely to develop leukopenia (OR 2.969, 95% CI 1.028-8.575, p = 0.044) after receiving at least two cycles of T + GC. However, these significant differences were not observed in thrombocytopenia and anemia. There were no significant differences in the tumor response and grade 3-4 hematological toxicity between patients with sarcopenia and those without sarcopenia. CONCLUSIONS: Patients with sarcopenia were more likely to develop leukopenia after receiving T + GC. There were no notable alterations observed in relation to anemia or thrombocytopenia. No significant difference was found between the sarcopenia group and non-sarcopenia group in terms of tumor response and grade 3-4 hematological toxicity.

Tuning active sites on biochars for remediation of mercury-contaminated soil: A comprehensive review.

Mercury (Hg) contamination is acknowledged as a global issue and has generated concerns globally due to its toxicity and persistence. Tunable surface-active sites (SASs) are one of the key features of efficient BCs for Hg remediation, and detailed documentation of their interactions with metal ions in soil medium is essential to support the applications of functionalized BC for Hg remediation. Although a specific active site exhibits identical behavior during the adsorption process, a systematic documentation of their syntheses and interactions with various metal ions in soil medium is crucial to promote the applications of functionalized biochars in Hg remediation. Hence, we summarized the BC's impact on Hg mobility in soils and discussed the potential mechanisms and role of various SASs of BC for Hg remediation, including oxygen-, nitrogen-, sulfur-, and X (chlorine, bromine, iodine)- functional groups (FGs), surface area, pores and pH. The review also categorized synthesis routes to introduce oxygen, nitrogen, and sulfur to BC surfaces to enhance their Hg adsorptive properties. Last but not the least, the direct mechanisms (e.g., Hg- BC binding) and indirect mechanisms (i.e., BC has a significant impact on the cycling of sulfur and thus the Hg-soil binding) that can be used to explain the adverse effects of BC on plants and microorganisms, as well as other related consequences and risk reduction strategies were highlighted. The future perspective will focus on functional BC for multiple heavy metal remediation and other potential applications; hence, future work should focus on designing intelligent/artificial BC for multiple purposes.

Negative family and interpersonal relationship are associated with centromedial amygdala functional connectivity alterations in adolescent depression.

The amygdala, known for its functional heterogeneity, plays a critical role in the neural mechanism of adolescent major depressive disorder (aMDD). However, changes in its subregional functional networks in relation to stressful factors remain unclear. We recruited 78 comorbidity-free, medication-naive aMDD patients and 40 matched healthy controls (HC) to explore changes in resting-state functional connectivity (FC) across four amygdala subregions: the centromedial nucleus (CM), the basolateral nucleus (LB), the superficial nucleus (SF), and the amygdalostriatal transition area (Astr). Then, we performed partial correlation analysis to investigate the relationship between amygdala subregional FC and stressful factors as measured by the Chinese Version of Family Environment Scale (FES-CV) and the Adolescent Self-Rated Life Events Scale (ASLEC). Compared to HC, aMDD patients demonstrated significantly decreased functional connectivity between the left CM and left precentral gyrus, as well as between left SF and left precentral gyrus, and between left LB and posterior cingulate gyrus (PCC)/precuneus. In aMDD group, left CM-precentral gyrus FC exhibited negative correlation with interpersonal relationship and punishment, and positive correlation with family cohesion and expressiveness. This study reveals distinct patterns of abnormal functional connectivity among amygdala subregions in aMDD. Our findings suggest that the CM network, in particular, may be involved in stress-related factors in aMDD, which provide a potential target for the prevention and treatment of adolescent depression.

Abnormal sleep patterns are associated with depressive symptoms in Chinese community-dwelling older adults.

OBJECTIVE: Depression is an important public health issue among older adults, often associated with their sleep-related problems. We aimed to investigate the association between sleep-related problems and depressive symptoms among Chinese community-dwelling older adults. METHODS: This cross-sectional study utilized self-reported data from 2896 participants (aged ≥60 years) from Shanghai, China. Nocturnal sleep duration and difficulty initiating sleep (DIS) symptoms were obtained through face-to-face questionnaires. Nocturnal sleep duration was categorized as 'short' (<7 h), 'normal' (7-8 h), and 'long' (>8 h). Subsequently, the 3 groups were further divided into 6 groups based on the presence of DIS, and the combined sleep behaviors were termed 'sleep patterns'. Logistic regression was conducted to assess the association of sleep variables and sleep patterns with the risk of depressive symptoms. RESULTS: Compared to the reference group, 'short sleep duration' and DIS symptoms were associated with depressive symptoms (with odds ratios (OR) of 1.50 and 1.79, respectively, with 95% confidence intervals (CI) of 1.14-1.97 and 1.39-2.31). When compared to 'normal sleep duration without DIS', both 'short sleep duration with DIS' (OR = 2.60, 95% CI: 1.81-3.72) and 'normal sleep duration with DIS' (OR = 1.60, 95% CI: 1.03-2.49) were statistically associated with depressive symptoms in adjusted regression models. CONCLUSION: Short sleep duration and DIS symptoms were found to be associated with depressive symptoms. Combining DIS symptoms with sleep duration, DIS was identified as a risk factor for elevated depressive symptoms in individuals with short and normal sleep durations. In managing depressive symptoms, it is imperative to thoroughly evaluate insomnia and nighttime sleep, which can provide valuable insights for nursing and medical policy.

Physicochemical Characterization, Antioxidant and Anticancer Activity Evaluation of an Acidic Polysaccharide from Alpinia officinarum Hance.

AHP-3a, a triple-helix acidic polysaccharide isolated from Alpinia officinarum Hance, was evaluated for its anticancer and antioxidant activities. The physicochemical properties and structure of AHP-3a were investigated through gel permeation chromatography, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. The weight-average molecular weight of AHP-3a was 484 kDa, with the molar percentages of GalA, Gal, Ara, Xyl, Rha, Glc, GlcA, and Fuc being 35.4%, 21.4%, 16.9%, 11.8%, 8.9%, 3.1%, 2.0%, and 0.5%, respectively. Based on the results of the monosaccharide composition analysis, methylation analysis, and NMR spectroscopy, the main chain of AHP-3a was presumed to consist of (1→4)-α-D-GalpA and (1→2)-α-L-Rhap residues, which is a pectic polysaccharide with homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) structural domains containing side chains. In addition, the results of the antioxidant activity assay revealed that the ability of AHP-3a to scavenge DPPH, ABTS, and OH free radicals increased with an increase in its concentration. Moreover, according to the results from the EdU, wound healing, and Transwell assays, AHP-3a can control the proliferation, migration, and invasion of HepG2 and Huh7 hepatocellular carcinoma cells without causing any damage to healthy cells. Thus, AHP-3a may be a natural antioxidant and anticancer component.

Polymer Nanoparticles with 2-HP-ß-Cyclodextrin for Enhanced Retention of Uptake into HCE-T Cells.

Triamcinolone acetonide (TA), a medium-potency synthetic glucocorticoid, is primarily employed to treat posterior ocular diseases using vitreous injection. This study aimed to design novel ocular nanoformulation drug delivery systems using PLGA carriers to overcome the ocular drug delivery barrier and facilitate effective delivery into the ocular tissues after topical administration. The surface of the PLGA nanodelivery system was made hydrophilic (2-HP-ß-CD) through an emulsified solvent volatilization method, followed by system characterization. The mechanism of cellular uptake across the corneal epithelial cell barrier used rhodamine B (Rh-B) to prepare fluorescent probes for delivery systems. The triamcinolone acetonide (TA)-loaded nanodelivery system was validated by in vitro release behavior, isolated corneal permeability, and in vivo atrial hydrodynamics. The results indicated that the fluorescent probes, viz., the Rh-B-(2-HP-ß-CD)/PLGA NPs and the drug-loaded TA-(2-HP-ß-CD)/PLGA NPs, were within 200 nm in size. Moreover, the system was homogeneous and stable. The in vitro transport mechanism across the epithelial barrier showed that the uptake of nanoparticles was time-dependent and that NPs were actively transported across the epithelial barrier. The in vitro release behavior of the TA-loaded nanodelivery systems revealed that (2-HP-ß-CD)/PLGA nanoparticles could prolong the drug release time to up to three times longer than the suspensions. The isolated corneal permeability demonstrated that TA-(2-HP-ß-CD)/PLGA NPs could extend the precorneal retention time and boost corneal permeability. Thus, they increased the cumulative release per unit area 7.99-fold at 8 h compared to the suspension. The pharmacokinetics within the aqueous humor showed that (2-HP-ß-CD)/PLGA nanoparticles could elevate the bioavailability of the drug, and its Cmax was 51.91 times higher than that of the triamcinolone acetonide aqueous solution. Therefore, (2-HP-ß-CD)/PLGA NPs can potentially elevate transmembrane uptake, promote corneal permeability, and improve the bioavailability of drugs inside the aqueous humor. This study provides a foundation for future research on transocular barrier nanoformulations for non-invasive drug delivery.

A novel collaborative self-supervised learning method for radiomic data.

The computer-aided disease diagnosis from radiomic data is important in many medical applications. However, developing such a technique relies on labeling radiological images, which is a time-consuming, labor-intensive, and expensive process. In this work, we present the first novel collaborative self-supervised learning method to solve the challenge of insufficient labeled radiomic data, whose characteristics are different from text and image data. To achieve this, we present two collaborative pretext tasks that explore the latent pathological or biological relationships between regions of interest and the similarity and dissimilarity of information between subjects. Our method collaboratively learns the robust latent feature representations from radiomic data in a self-supervised manner to reduce human annotation efforts, which benefits the disease diagnosis. We compared our proposed method with other state-of-the-art self-supervised learning methods on a simulation study and two independent datasets. Extensive experimental results demonstrated that our method outperforms other self-supervised learning methods on both classification and regression tasks. With further refinement, our method will have the potential advantage in automatic disease diagnosis with large-scale unlabeled data available.

Impairments in intrinsic functional networks in type 2 diabetes: A meta-analysis of resting-state functional connectivity.

Type 2 diabetes mellitus (T2DM) is associated with abnormal communication among large-scale brain networks, revealed by resting-state functional connectivity (rsFC), with inconsistent results between studies. We performed a meta-analysis of seed-based rsFC studies to identify consistent network connectivity alterations. Thirty-three datasets from 30 studies (1014 T2DM patients and 902 healthy controls [HC]) were included. Seed coordinates and between-group effects were extracted, and the seeds were divided into networks based on their location. Compared to HC, T2DM patients showed hyperconnectivity and hypoconnectivity within the DMN, DMN hypoconnectivity with the affective network (AN), ventral attention network (VAN) and frontal parietal network, and DMN hyperconnectivity with the VAN and visual network. T2DM patients also showed AN hypoconnectivity with the somatomotor network and hyperconnectivity with the VAN. T2DM illness durations negatively correlated with within-DMN rsFC. These DMN-centered impairments in large-scale brain networks in T2DM patients may help to explain the cognitive deficits associated with T2DM.