Search

Abstract In a multicenter case–control investigation, we assessed the efficacy of the Electrooculogram Signal Analysis (EOG-SA) method, which integrates attention-related visual evocation, electrooculography, and nonlinear analysis, for distinguishing between intellectual and developmental disabilities (IDD) and typical development (TD) in children. Analyzing 127 participants (63 IDD, 64 TD), we applied nonlinear dynamics for feature extraction. Results indicated EOG-SA’s capability to distinguish IDD, with higher template thresholds and Correlation Dimension values correlating with clinical severity. The template threshold proved a robust indicator, with higher values denoting severe IDD. Discriminative metrics showed areas under the curve of 0.91 (template threshold) and 0.85/0.91 (D2), with sensitivities and specificities of 77.6%/95.9% and 93.5%/71.0%, respectively. EOG-SA emerges as a promising tool, offering interpretable neural biomarkers for early and nuanced diagnosis of IDD.

Abstract Background To make the best use of health resources, it is crucial to understand the healthcare needs of a population—including how needs will evolve and respond to changing epidemiological context and patient behaviour—and how this compares to the capabilities to deliver healthcare with the existing workforce. Existing approaches to planning either rely on using observed healthcare demand from a fixed historical period or using models to estimate healthcare needs within a narrow domain (e.g., a specific disease area or health programme). A new data-grounded modelling method is proposed by which healthcare needs and the capabilities of the healthcare workforce can be compared and analysed under a range of scenarios: in particular, when there is much greater propensity for healthcare seeking. Methods A model representation of the healthcare workforce, one that formalises how the time of the different cadres is drawn into the provision of units of healthcare, was integrated with an individual-based epidemiological model—the Thanzi La Onse model—that represents mechanistically the development of disease and ill-health and patients’ healthcare seeking behaviour. The model was applied in Malawi using routinely available data and the estimates of the volume of health service delivered were tested against officially recorded data. Model estimates of the “time needed” and “time available” for each cadre were compared under different assumptions for whether vacant (or established) posts are filled and healthcare seeking behaviour. Results The model estimates of volume of each type of service delivered were in good agreement with the available data. The “time needed” for the healthcare workforce greatly exceeded the “time available” (overall by 1.82-fold), especially for pharmacists (6.37-fold) and clinicians (2.83-fold). This discrepancy would be largely mitigated if all vacant posts were filled, but the large discrepancy would remain for pharmacists (2.49-fold). However, if all of those becoming ill did seek care immediately, the “time needed” would increase dramatically and exceed “time supply” (2.11-fold for nurses and midwives, 5.60-fold for clinicians, 9.98-fold for pharmacists) even when there were no vacant positions. Conclusions The results suggest that services are being delivered in less time on average than they should be, or that healthcare workers are working more time than contracted, or a combination of the two. Moreover, the analysis shows that the healthcare system could become overwhelmed if patients were more likely to seek care. It is not yet known what the health consequences of such changes would be but this new model provides—for the first time—a means to examine such questions.

Objective: The objective of this study is to explore the optimal ratio of Glycyrrhiza Radix (GR, Glycyrrhizae radix et Rhizoma) and Platycodonis Radix (PR, Platycodon grandiflorum A. DC) and its potential mechanism for treating respiratory syncytial virus (RSV) pneumonia in mice. Materials and Methods: Aqueous extracts of GR-PR with different ratios (1:1, 2:1, and 1:2 w/w) were prepared and analyzed using ultra-performance liquid chromatography coupled with a linear ion trap quadrupole Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap-MS). The effects of various ratios of GR-PR were investigated in BALB/c mice. Changes in body weight were recorded, histopathology was evaluated, and relative mRNA levels of inflammatory mediators were measured. In addition, lipidomic analysis was performed to investigate the effects of GR-PR on lipids and related signaling pathways. Results: The aqueous extracts of GR-PR improved body weight and reduced lung inflammation compared to the RSV group, with the optimal therapeutic effect achieved with a 1:2 ratio of GR to PR. RSV infection disrupted several serum lipids, particularly sphingomyelin (SM) and ceramide (CER), which were partially restored by GR-PR administration. Overall, GR-PR significantly improved the metabolic disorder of SM-CER-induced inflammation and apoptosis, along with decreased mRNA levels of caspase-1, nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3), and toll-like receptor 3 (TLR3), and protein expression of NLRP3, pro-caspase-1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), interleukin-1β (IL-1β), IL-18, gasdermin D (GSDMD), nuclear factor kappa-B (NF-κB), Bcl2-associated X protein (BAX), caspase-3, and caspase-8. The involvement of the TLR3-NF-κB-NLRP3 signaling pathway in this process was confirmed. Conclusions: The aqueous extracts of GR-PR, particularly at a ratio of 1:2, demonstrate potential therapeutic benefits for RSV-induced pneumonia by improving lipid metabolism and inhibiting the activation of TLR3-NF-κB-NLRP3 signaling pathway.

Abstract Living kidney donors have been regarded as those people having earned the healthiest status level after having undergone scrutiny. Although one’s post-donation GFR is expected to fall to 50% of their pre-donation value, it is well documented that there is a compensatory increase in GFR which subsequently reaches approximately 60–70% of the donor’s pre-donation value. Data regarding gout/hyperuricemia in living kidney donors has remained scarce until now. This study involved kidney donors enrolled within the years 2000 to 2017, where those who were selected to be matched to those in group of case cohort by age, year of index date, gender and co-morbidity were considered as the control cohort. During the 17-year study period 2,716 participants were enrolled. Results revealed that kidney donors experienced a risk of new onset gout/ hyperuricemia (adjusted HR = 1.73; 95%CI = 1.27, 2.36), and new onset CKD (adjusted HR = 6.7; 95% CI = 4.4, 10.21) were found to be higher in kidney donors. Our findings suggest that people after kidney donation are significantly associated with a higher risk of new onset gout/hyperuricemia. Clinical professionals therefore need to be cautious of new onset gouy/hyperuricemia after donation surgery.

Abstract The CPT invariant vacuum states of a scalar field in de Sitter space, called α-vacua, are not unique. We explore the α-vacua from the quantum information perspective by a pair of static Unruh-DeWitt (UDW) detectors coupled to a scalar field with either monopole or dipole coupling, which are in time-like zero separation or space-like antipodal separation. The analytical form of the reduced final state of the UDW detector is derived. We study the entanglement harvesting and quantum discord of the reduced state, which characterize the quantum entanglement and quantum correlation of the underlying α-vacua, respectively. Our results imply that the quantum entanglement gravitated by de Sitter gravity behaves quite differently for time-like and space-like separations. It experiences “sudden death” for the former and grows for the latter as the measuring time or the value of α increases. This demonstrates the nonlocal nature of quantum entanglement. For the quantum discord, we find no “sudden death” behavior, and it experiences superhorizon suppression, which explains the superhorizon decoherence in the inflationary universe scenario. Overall, the time-like or space-like quantum entanglement and correlation behave differently on their dependence of α, measuring time and spectral gaps, with details discussed in this work.

Abstract Objective Transfer RNA-derived fragments (tRFs) are short non-coding RNA (ncRNA) sequences, ranging from 14 to 30 nucleotides, produced through the precise cleavage of precursor and mature tRNAs. While tRFs have been implicated in various diseases, including cancer, their role in lung adenocarcinoma (LUAD) remains underexplored. This study aims to investigate the impact of tRF-Val-CAC-010, a specific tRF molecule, on the phenotype of LUAD cells and its role in tumorigenesis and progression in vivo. Methods The expression level of tRF-Val-CAC-010 was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Specific inhibitors and mimics of tRF-Val-CAC-010 were synthesized for transient transfection. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8), while cell invasion and migration were evaluated through Transwell invasion and scratch assays. Flow cytometry was utilized to analyze cell cycle and apoptosis. The in vivo effects of tRF-Val-CAC-010 on tumor growth and metastasis were determined through tumor formation and metastasis imaging experiments in nude mice. Results The expression level of tRF-Val-CAC-010 was upregulated in A549 and PC9 LUAD cells (P

Abstract Background A better understanding of the association between chronic kidney disease (CKD) and glaucoma is required to optimize clinical outcomes. Therefore, this study aimed to investigate the association of chronic kidney disease (CKD) with new diagnoses of glaucoma over time from January 2009 to December 2019. Method This retrospective propensity-matched cohort study utilizing Taiwanese electronic health records examined the incidence of newly diagnosed glaucoma in patients with and without chronic kidney disease (CKD). The exposure variable was the diagnosis of CKD, identified through diagnostic codes. The primary outcome was the incidence of new-onset glaucoma. Subgroup analyses on glaucoma risk included age, gender, comorbidities, glaucoma subtypes, and dialysis status. Statistical analyses included Kaplan–Meier analysis, Cox proportional hazards models, and Poisson regression models, with the associated hazard ratios and confidence intervals reported. Results Seven hundred twenty-three thousand two hundred sixteen patients with CKD (42.3% female; mean [SD] age at index, 66.3 [15.6] years) and 723,216 patients without CKD (42.3% female; mean [SD] age at index, 66.3 [15.7]) were recruited. We showed a significantly increased risk of glaucoma irrespective of subtypes in CKD patients compared to those without CKD (HR: 1.29 [CI: 1.26–1.32], p 80: aHR 1.29 [CI: 1.21–1.37]); all income brackets and all urbanization status were associated with significantly increased risk of glaucoma from among the CKD cohort when compared to their respective non-CKD cohort (p

Abstract The high-intactness and ultraclean fabrication of suspended 2D materials has always been a challenge due to their atomically thin nature. Here, we present a universal polymer-free transfer approach for fabricating suspended 2D materials by using volatile micro-molecule cyclododecane as the transfer medium, thus ensuring the ultraclean and intact surface of suspended 2D materials. For the fabricated monolayer suspended graphene, the intactness reaches 99% for size below 10 µm and suspended size reaches 36 µm. Owing to the advantages of ultra-cleanness and large size, the thermal conductivity reaches 4914 $${\rm{W}}\,{{\rm{m}}}^{-1}{{\rm{K}}}^{-1}$$ W m − 1 K − 1 at 338 K. Moreover, this strategy can also realize efficient batch transfer of suspended graphene and is applicable for fabricating other 2D suspended materials such as MoS2. Our research not only establishes foundation for potential applications and investigations of intrinsic properties of large-area suspended 2D materials, but also accelerates the wide applications of suspended graphene grid in ultrahigh-resolution TEM characterization.

Abstract Background Forest soils are usually highly weathered and abundant in mineral-weathering bacteria, which have not been used to mobilize soil minerals for crop production. Here, we used an acidic forest soil with low available phosphorus (P), potassium (K), and silicon (Si) to isolate bacteria capable of co-solubilizing P, K, and Si (PKSi-solubilizing) and the model rice plant to test their potential to mobilize soil P, K, and Si for crop nutrition. Results Six PKSi-solubilizing strains representative of common mineral-weathering proteobacteria taxa (genera Burkholderia, Paraburkholderia, Collimonas, Pseudomonas, and Agrobacterium) were screened out. They showed diverse P-, K-, or Si-solubilizing activities and produced diverse organic acids. Their mineral-solubilizing activities were positively correlated with the levels of medium pH reduction and gluconic acid production. They promoted the growth of rice seedlings grown in the forest soil by increasing soil available P and Si, plant P, K, and Si cumulative contents and dry weight, and the corresponding root-to-shoot ratios. The growth of rice seedlings alone and with the inoculated PKSi-solubilizing stains in the acidic forest soil did not reduce the soil pH. Conclusions The forest soil with low available P, K, and Si is a valuable resource for high-performance PKSi-solubilizing bacteria improving soil fertility and crop nutrition. The PKSi-solubilizing bacteria screened out can promote rice seedling growth by mobilizing P, K, and Si from soil to plant in the acidic soil with low available P, K, and Si. They show potentials to mitigate soil P, K, and Si deficiency and promote crop growth, and to recover soluble P, K, and Si from chemical fertilizers and improve the use efficiency of chemical fertilizers, thus reducing the input of chemical fertilizers. They may retard soil acidification by Si-solubilization and improve soil quality. Graphical Abstract

Abstract Background Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. Methods Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. Results We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. Conclusion Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.

Abstract Background and Objective The complex risk factors of liver injury have prevented the establishment of causal relationships. This study aimed to explore the effects of antidepressant class, cumulative days of medication exposure, presence of comorbidities, and the use of confounding drugs on the risk of antidepressant-induced liver injury. Methods The population-based case–control study sample included individuals registered on the Taiwan National Health Insurance Database between 2000 and 2018. Hospitalized patients with suspected drug-induced liver injury were considered as cases, while control subjects were matched 1:1 by age, gender, and index date (the first observed diagnosis of liver injury). Multivariable regression models were performed to evaluate the association between antidepressants and liver injury. Results The findings showed that antidepressant users exhibited a higher risk of liver injury (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.12–1.20), particularly those prescribed non-selective serotonin reuptake inhibitors (NSRIs; aOR 1.05; 95% CI 1.01–1.10), selective serotonin reuptake inhibitors (SSRIs; aOR 1.22; 95% CI 1.16–1.29), serotonin-norepinephrine reuptake inhibitors (SNRIs; aOR 1.18; 95% CI 1.13–1.24), and others (aOR 1.27; 95% CI 1.14–1.42). Moreover, cases exhibited a more significant proportion of antidepressant usage and longer durations of treatment compared with controls. The risk of liver injury was higher in the first 30 days of use across all classes of antidepressants (aOR 1.24; 95% CI 1.18–1.29). Conclusion SSRIs or SNRIs are commonly used to treat depression and other psychological disorders, and consideration of their potential effects on the liver is essential.

Abstract Following a recent proposal to describe inelastic eikonal scattering processes in terms of gravitationally dressed elastic eikonal amplitudes, we motivate a collinear double graviton dressing and investigate its properties. This is derived from a generalized Wilson line operator in the worldline formalism by integrating over fluctuations of the eikonal trajectories of external particles in gravitationally interacting theories. The dressing can be expressed as a product of exponential terms — a coherent piece with contributions to all odd orders in the gravitational coupling constant and a term quadratic in graviton modes, with the former providing classical gravitational wave observables. In particular, the coherent dressing involves O κ 3 $$ \mathcal{O}\left({\kappa}^3\right) $$ subleading double graviton corrections to the Weinberg soft factor. We use this dressing to derive expressions for the waveform, radiative momentum spectrum and angular momentum. In a limiting case of the waveform, we derive the nonlinear memory effect resulting from the emission of nearly soft gravitons from a scattering process.

Abstract In this note, we propose a factorization formula for gauge-theory scattering amplitudes up to two loops in the high-energy boosted limit. Our formula extends existing results in the literature by incorporating the contributions from massive loops. We derive the new ingredients in our formula using the method of regions with analytic regulators for the rapidity divergences. We verify our results with various form factors and the scattering amplitudes for top-quark pair production. Our results can be used to obtain approximate expressions for complicated two-loop massive amplitudes from simpler massless ones, and can be used to resum the mass logarithms to all orders in the coupling constant.

CD44 is associated with a high risk of metastasis, recurrence, and drug resistance in various cancers. Here we report that platelet endothelial aggregation receptor 1 (PEAR1) is a CD44 chaperone protein that protected CD44 from endocytosis-mediated degradation and enhances cleavage of the CD44 intracellular domain (CD44-ICD). Furthermore, we found that lysyl oxidase-like protein 2 (LOXL2), an endogenous ligand of PEAR1, bound to the PEAR1-EMI domain and facilitated the interaction between PEAR1 and CD44 by inducing PEAR1 Ser891 phosphorylation in a manner that was independent of its enzyme activity. Levels of PEAR1 protein and PEAR1 phosphorylation at Ser891 were increased in patients with triple-negative breast cancer (TNBC), were positively correlated with expression of LOXL2 and CD44, and were negatively correlated with overall survival. The level of PEAR1 Ser891 phosphorylation was identified as the best independent prognostic factor in TNBC patients. The prognostic efficacy of the combination of PEAR1 phosphorylation at Ser891 and CD44 expression was superior to that of PEAR1 phosphorylation at Ser891 alone. Blocking the interaction between LOXL2 and PEAR1 with monoclonal antibodies significantly inhibited TNBC metastasis, representing a promising therapeutic strategy for TNBC., Introduction Breast cancer is the most prevalent malignancy in women, and its incidence is increasing (1). Of particular concern is triple-negative breast cancer (TNBC), which is an exceptionally aggressive and [...]

It is unknown which posttranscriptional regulatory mechanisms are required for oncogenic competence. Here, we show that the LIN28 family of RNA-binding proteins (RBPs), which facilitate posttranscriptional RNA metabolism within ribonucleoprotein networks, is essential for the initiation of diverse oncotypes of hepatocellular carcinoma (HCC). In HCC models driven by [NRAS.sup.G12V]/Tp53, CTNNB1/YAP/TpS3, or AKT/Tp53, mice without Lin28a and Lin28b were markedly impaired in cancer initiation. We biochemically defined an oncofetal regulon of 15 factors connected to LIN28 through direct mRNA and protein interactions. Interestingly, all were RBPs and only 1 of 15 was a Let-7 target. Polysome profiling and reporter assays showed that LIN28B directly increased the translation of 8 of these 15 RBPs. As expected, overexpression of LIN28B and IGFBP1-3 was able to genetically rescue cancer initiation. Using this platform to probe components downstream of LIN28, we found that 8 target RBPs were able to restore [NRAS.sup.G12V]/Tp53 cancer formation in Lin28a/Lin28b-deficient mice. Furthermore, these LIN28B targets promote cancer initiation through an increase in protein synthesis. LIN28B, central to an RNP regulon that increases translation of RBPs, is important for tumor initiation in the liver., Introduction In chronically inflamed tissues subject to field cancerization, tumor initiation occurs repeatedly in different parts of the organ over long time periods. For cancer mutations to drive transformation, cells [...]

BackgroundMost of patients with prostate cancer (PCa) are elderly and have a long course of disease. Preoperative assessment of the patient's clinical nutritional status facilitates early intervention and improves patient prognosis.MethodsWe assessed the nutritional status of PCa patients utilizing the Nutritional Risk Index (NRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT) scoring systems. Survival comparisons between groups were conducted using Kaplan-Meier curve analysis and log-rank tests, while Cox proportional hazards regression analysis was employed to identify independent prognostic factors. Furthermore, we implemented bootstrap-based optimism correction methods to validate the scoring systems and applied decision curve analysis to evaluate the non-inferiority of these three clinical nutrition scoring systems relative to the conventional American Joint Committee on Cancer (AJCC) staging.ResultsIn this study, malnutrition was diagnosed in 31.51% of the patients using the NRI, 13.02% using the PNI, and 88.28% using the CONUT score. After adjusting for confounders, normal nutritional status as defined by NRI and PNI emerged as an independent prognostic factor for prostate-specific antigen progression-free survival (PSA-PFS). However, nutritional status assessed by CONUT inaccurately predicted PSA-PFS. Normal nutritional status, as determined by all three scoring systems, was found to be an independent prognostic factor for progression-free survival (PFS). Following adjustments for optimistic estimates, the C-index for NRI in predicting both PSA-PFS and PFS remained the highest among the three scoring systems. The results of the DCA indicated that the C-index of all three scoring systems was higher than that of AJCC stage.ConclusionsNRI, PNI, and CONUT are convenient and clinically applicable scoring systems. A clinical malnutrition intervention may improve the prognosis of prostate cancer patients.

Background: As a rare subcutaneous infection, protothecosis is easily misdiagnosed. Similar to other subcutaneous infection, there is no unified standard for treatment, for cases not suitable for surgery, clinicians often use antifungal drugs based on their experience, and the course of treatment varies from several months to several years. Based on the fact that there are few relevant materials and researches on photodynamic therapy (PDT), we conducted a study based on a clinical case that used oral itraconazole combined with 5-aminolevylinic acid photodynamic therapy (ALA-PDT) to treat a patient with cutaneous protothecosis caused by Prototheca wicherhamii. Methods: Different concentrations of ALA and different light doses were used to investigate the effects of ALA-PDT on the growth inhibition of P. wickerhamii in vitro with Colony-counting Methods. And we used transmission electron microscopy (TEM) to visualize the structural changes and the effects of ALA-PDT treating on cellular structures of the P. wickerhamii. Futher, we performed the susceptibility test of P. wickerhamii to itraconazole before and after ALA-PDT in vitro. Results: We have successfully treated a patient with cutaneous protothecosis caused by P. wickerhamii by using combination therapy in a total of 9-week course of treatment. In vitro, ALA-PDT can inhibit the growth of P. wickerhamii when the ALA concentration was 5 mg/mL (P < 0.01), and this effect became stronger as the concentration of ALA or light dose is increased. Using TEM, we confirmed that ALA-PDT can disrupt the cell wall structure and partition structure of P. wickerhamii, which may contribute to its inhibitory effect. Further studies showed that the MIC of itraconazole for P. wickerhamii was decreased after ALA-PDT. Conclusions: ALA-PDT combined with oral itraconazole can be used to treat cutaneous protothecosis. Accordingly, ALA-PDT can destroy the cell wall and partition structure of P. wickerhamii leading to an inhibitory effect on it in vitro, and the effect is enhanced with the increase of ALA concentration and light dose. Also, the sensitivity of P. wickerhamii to itraconazole is observed increased after ALA-PDT. So our study provides a theoretical basis for the promising treatment against cutaneus protothecosis.