Diabetic uveopathy.

Diabetes can involve several ocular structures -- including the cornea, lens, and retina -- and cause vascular and neural changes in these tissues. Although retinopathy is the most common ocular complication of diabetes, uveopathy can also be observed. This includes vascular, neural, muscular, and basement membrane changes. The main clinical manifestations of diabetic uveopathy are anterior uveitis and abnormal pupillary dynamics. Fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography are ideal for the imaging of vascular changes of the iris and choroid, while dynamic pupillometry is a simple screening tool to detect neuropathy. Additionally, ultrasound biomicroscopy can provide clear images of the ciliary body. Iris abnormalities, primarily angiopathy and neuropathy, can appear as alterations in vascular diameter, neovascularization, and abnormal pupillary dynamics. Choroidal abnormalities primarily affect blood vessels, including alterations in vascular diameter, microaneurysm formation, and neovascularization. The abnormal manifestations in the ciliary body include a decrease in vessel count, alterations in their diameter, isolated angiomatous dilatation, and diffuse thickening of the basal membrane of the pigment epithelium.

Application of MIDD to accelerate the development of anti-infectives: Current status and future perspectives.

This review examines the role of model-informed drug development (MIDD) in advancing antibacterial and antiviral drug development, with an emphasis on the inclusion of host system dynamics into modeling efforts. Amidst the growing challenges of multidrug resistance and diminishing market returns, innovative methodologies are crucial for continuous drug discovery and development. The MIDD approach, with its robust capacity to integrate diverse data types, offers a promising solution. In particular, the utilization of appropriate modeling and simulation techniques for better characterization and early assessment of drug resistance are discussed. The evolution of MIDD practices across different infectious disease fields is also summarized, and compared to advancements achieved in oncology. Moving forward, the application of MIDD should expand into host system dynamics as these considerations are critical for the development of "live drugs" (e.g. chimeric antigen receptor T cells or bacteriophages) to address issues like antibiotic resistance or latent viral infections.

Serum ganciclovir drug exposure in children receiving standard ganciclovir dosing.

Intravenous ganciclovir (GCV) is used for the treatment of cytomegalovirus (CMV) infection in immunocompromised children. Although the therapeutic target for treatment is unclear, studies have shown a serum area under the concentration-time curve (AUC24h) ≥40 mg/L·h correlates with effective CMV prevention. This study aimed to externally validate existing GCV population pharmacokinetic (PopPK) models and develop a model if needed and evaluate the serum AUC24h achieved with standard GCV dosing and propose an optimized dosing strategy for immunocompromised children. Ganciclovir drug monitoring data from two pediatric hospitals were retrospectively collected, and published pediatric PopPK models were externally validated. The population AUC24h with standard GCV dosing (5 mg/kg twice daily) was calculated, and an optimized dosing strategy was determined using Monte Carlo simulations to achieve an AUC24h between 40 and 100 mg/L·h. Overall, 161 samples from 23 children with a median (range) age of 9.0 years (0.4-17.0) and weight of 28.2 kg (5.6-73.3) were analyzed. Transferability of published pediatric PopPK models was limited. Thus, a one-compartment model with first-order absorption and elimination with weight and serum creatinine as covariates was developed. The median (5th-95th percentiles) steady state AUC24h with standard dosing was 38.3 mg/L·h (24.8-329.2) with 13 children having an AUC24h <40 mg/L·h, particularly those aged <4 years (8/13). An optimized simulated GCV dosing regimen, ranging from 2 to 13 mg/kg twice daily for children with normal renal function, achieved 61%-78% probability of target attainment. Standard GCV dosing likely results in inadequate drug exposure in more than half of the children, particularly those aged <4 years. An optimized dosing regimen has been proposed for clinical validation.

Adaptive roles of cytokinins in enhancing plant resilience and yield against environmental stressors.

Innovative agricultural strategies are essential for addressing the urgent challenge of food security in light of climate change, population growth, and various environmental stressors. Cytokinins (CKs) play a pivotal role in enhancing plant resilience and productivity. These compounds, which include isoprenoid and aromatic types, are synthesized through pathways involving key enzymes such as isopentenyl transferase and cytokinin oxidase. Under abiotic stress conditions, CKs regulate critical physiological processes by improving photosynthetic efficiency, enhancing antioxidant enzyme activity, and optimizing root architecture. They also reduce the levels of reactive oxygen species and malondialdehyde, resulting in improved plant performance and yield. CKs interact intricately with other phytohormones, including abscisic acid, ethylene, salicylic acid, and jasmonic acid, to modulate stress-responsive pathways. This hormonal cross-talk is vital for finely tuning plant responses to stress. Additionally, CKs influence nutrient uptake and enhance responses to heavy metal stress, thereby bolstering overall plant resilience. The application of CKs helps plants maintain higher chlorophyll levels, boost antioxidant systems, and promote root and shoot growth. The strategic utilization of CKs presents an adaptive approach for developing robust crops capable of withstanding diverse environmental stressors, thus contributing to sustainable agricultural practices and global food security. Ongoing research into the mechanisms of CK action and their interactions with other hormones is essential for maximizing their agricultural potential. This underscores the necessity for continued innovation and research in agricultural practices, in alignment with global goals of sustainable productivity and food security.

Regulated anthocyanin release through novel pH-responsive peptide hydrogels in simulated digestive environment.

The instability of anthocyanins significantly reduces their bioavailability as food nutrients. This proof-of-concept study aimed to develop efficient carriers for anthocyanins to overcome this challenge. Characterization of the hydrogels via SEM (scanning electron microscope) and rheological analysis revealed the formation of typical gel structures. MTT (methyl thiazolyl tetrazolium) and hemolysis assays confirmed that their high biocompatibility. Encapsulation efficiency analysis and fluorescence microscopy images demonstrated successful and efficient encapsulation of anthocyanins by pH-responsive hydrogels. Stability studies further validated the effect of peptide hydrogels in helping anthocyanin molecules withstand factors such as gastric acid, high temperatures, and heavy metals. Subsequently, responsive studies in simulated gastric (intestinal) fluid demonstrated that the pH-responsive peptide hydrogels could protect anthocyanin molecules from gastric acid while achieving rapid and complete release in intestinal fluid environments. These results indicate that these peptide hydrogels could stabilize anthocyanins and facilitate their controlled release, potentially leading to personalized delivery systems.

Ivermectin therapy for young children with scabies infection: a multicentre phase 2 non-randomized trial.

Background: Ivermectin, an effective treatment for scabies, is not licensed for children weighing <15 kg. Pharmacokinetic modelling has shown a 3 mg dose in young children (2-4 years, weighing 10-14 kg) achieves comparable drug exposure to a 200 µg/kg dose in children aged ≥5 years. This trial evaluated a 3 mg dose in young children. Methods: Multicentre, phase 2 trial in five health centres in Lao PDR. Children aged 2-4 years, weighing 10-14 kg with scabies received 3 mg ivermectin and had two plasma concentrations determined (Clinicaltrials.gov ID NCT05500326). On day 14, clinical outcomes and adverse effects were assessed, and a second dose given to complete treatment. The primary outcome was the mean plasma ivermectin exposure (AUC0-∞) after the first dose (compared to a historical control of Indigenous Australian children aged ≥5 years weighing ≥15 kg receiving 200 µg/kg). Secondary outcomes were clinical improvement and adverse effects. Findings: Overall, 100 children with a median age of 3.0 years (IQR 2.6-3.9) and weight of 11.9 kg (IQR 11.0-13.1) were enrolled. The mean observed ivermectin AUC0-∞ was comparable to the historical control group aged 5-11 years (815 µg h/L vs 953 µg h/L, p = 0.256). Complete resolution of scabies occurred in 90/99 children by day 14. Adverse effects were mild, occurring in 7/99. Interpretation: A 3 mg ivermectin dose in children aged 2-4 years and weighing 10-14 kg achieved a mean plasma AUC0-∞ comparable to older children, was highly effective in treating scabies and well tolerated. This study supports extending ivermectin treatment to younger children improving global efforts to control this neglected disease. Funding: Project funding provided by a Thrasher Foundation Early Career Research Award.

Performances of a novel BAF with ferromanganese oxide modified biochar (FMBC) as the carriers for treating antibiotics, nitrogen and phosphorus in aquaculture wastewater.

In this paper, a biological aerated filter (BAF) based on ferromanganese oxide-biochar (FMBC) was constructed to investigated the removal performance and mechanism for conventional pollutants and four kinds of antibiotic, in contrast of conventional zeolite loaded BAF (BAF-A) and bamboo biochar filled BAF (BAF-B). Results showed that the average removal efficiency of total nitrogen (TN), total phosphorus (TP) and antibiotics in a FMBC-BAF (named by BAF-C) were 52.97 ± 2.27%, 51.58 ± 1.92% and 70.36 ± 1.00% ~ 81.65 ± 0.99% respectively in running period (39-100 d), which were significantly higher than those of BAF-A and BAF-B. In the BAF-C, the expression of denitrification enzyme activities and the secretion of extracellular polymeric substance (EPS) especially polyprotein (PN) were effectively stimulated, as well as accelerated electron transfer activity (ETSA) and lower electrochemical impedance spectroscopy (EIS) were acquired. After 100 days of operation, the abundance of nitrogen, phosphorus and antibiotic removal functional bacteria like Sphingorhabdus (4.52%), Bradyrhizobium (1.98%), Hyphomicrobium (2.49%), Ferruginibacter (7.80%), unclassified_f_Blastoca tellaceae (1.84%), norank_f_JG30-KF-CM45 (6.82%), norank_f_norank_o_SBR1031 (2.43%), Nitrospira (2.58%) norank_f_Caldilineaceae (1.53%) and Micropruina (1.11%) were enriched. Mechanism hypothesis of enhanced performances of nutrients and antibiotics removal pointed that: The phosphorus was removed by adsorption and precipitation, antibiotics removal was mainly achieved through the combined action of adsorption and biodegradation, while nitrogen removal was realized by biologic nitrification and denitrification in a FMBC-BAF for aquaculture wastewater treatment.

Incompatible packaging signals and impaired protein functions hinder reassortment of bat H17N10 or H18N11 segment 7 with human H1N1 influenza A viruses.

Novel bat H17N10 and H18N11 influenza A viruses (IAVs) are incapable of reassortment with conventional IAVs during co-infection. To date, the underlying mechanisms that inhibit bat and conventional IAV reassortment remain poorly understood. Herein, we used the bat influenza M gene in the PR8 H1N1 virus genetic background to determine the molecular basis that restricts reassortment of segment 7. Our results showed that NEP and M1 from bat H17N10 and H18N11 can interact with PR8 M1 and NEP, resulting in mediating PR8 viral ribonucleoprotein (vRNP) nuclear export and formation of virus-like particles with single vRNP. Further studies demonstrated that the incompatible packaging signals (PSs) of H17N10 or H18N11 M segment led to the failure to rescue recombinant viruses in the PR8 genetic background. Recombinant PR8 viruses (rPR8psH18M and rPR8psH17M) containing bat influenza M coding region flanked with the PR8 M PSs were rescued but displayed lower replication in contrast to the parental PR8 virus, which is due to a low efficiency of recombinant virus uncoating correlating with the functions of the bat M2. Our studies reveal molecular mechanisms of the M gene that hinder reassortment between bat and conventional IAVs, which will help to understand the biology of novel bat IAVs. IMPORTANCE: Reassortment is one of the mechanisms in fast evolution of influenza A viruses (IAVs) and responsible for generating pandemic strains. To date, why novel bat IAVs are incapable of reassorting with conventional IAVs remains completely understood. Here, we attempted to rescue recombinant PR8 viruses with M segment from bat IAVs to understand the molecular mechanisms in hindering their reassortment. Results showed that bat influenza NEP and M1 have similar functions as respective counterparts of PR8 to medicating viral ribonucleoprotein nuclear export. Moreover, the incompatible packaging signals of M genes from bat and conventional IAVs and impaired bat M2 functions are the major reasons to hinder their reassortment. Recombinant PR8 viruses with bat influenza M open reading frames were generated but showed attenuation, which correlated with the functions of the bat M2 protein. Our studies provide novel insights into the molecular mechanisms that restrict reassortment between bat and conventional IAVs.

Anthropogenic impacts on polycyclic aromatic hydrocarbons in surface water: Evidence from the COVID-19 lockdown.

The lockdown restrictions against coronavirus disease 2019 (COVID-19) have led to unprecedented reductions in global anthropogenic activities. Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic combustion-induced pollutants, but the influence of anthropogenic responses to COVID-19 on PAH contamination remains largely unknown. Here we quantified the impacts of lockdown restrictions on 16PAH pollution based on the data in concentrations dissolved in the water phase and absorbed on the suspended particulate matter (SPM) in the Elbe River from 2015 to 2021 and determined the changes in source contributions classified by individual years and stations. Results show that the annual average PAH concentrations in water and SPM were determined as 0.055 µg·L-1 and 3.77 mg·kg-1 from 2015 to 2021, respectively. Pronounced declines in PAH on SPM (up to -18 %) were observed during the three lockdowns in Germany from 2020 to 2021. However, dramatic rebounds of anthropogenic activities during the removal of the lockdown led to increases (up to 29 %) in ∑16PAH concentrations compared to the same period in previous years. Through the source apportionment method, vehicle and coal emissions were the two most predominant sources of PAHs in the river. Vehicle contribution decreased during the lockdown, while coal emissions increased by 5 %. Health risks for three age groups were assessed as potential low risk and decreased by 18 % from 1.54 × 10-4 in 2015 to 1.27 × 10-4 in 2019, and rebounded to 1.40 × 10-4 in 2020-2021. The findings of this study highlight the strong consistency between PAH concentrations and anthropogenic intensity, implying that source control from improved cleaner production is an effective pathway for mitigating PAH contamination in the aquatic environment.

Beyond algorithms: The human touch machine-generated titles for enhancing click-through rates on social media.

Artificial intelligence (AI) has the potential to revolutionize various domains by automating language-driven tasks. This study evaluates the effectiveness of an AI-assisted methodology, called the "POP Title AI Five-Step Optimization Method," in optimizing content titles on the RED social media platform. By leveraging advancements in natural language generation, this methodology aims to enhance the impact of titles by incorporating emotional sophistication and cultural proficiency, addressing existing gaps in AI capabilities. The methodology entails training generative models using human-authored examples that align with the aspirations of the target audience. By incorporating popular keywords derived from user searches, the relevance and discoverability of titles are enhanced. Audience-centric filtering is subsequently employed to further refine the generated outputs. Furthermore, human oversight is introduced to provide essential intuition that AI systems alone may lack. A total of one thousand titles, generated by AI, underwent linguistic and engagement analyses. Qualitatively, 65% of the titles exhibited intrigue and conveyed meaning comparable to those generated by humans. However, attaining full emotional sophistication remained a challenge. Quantitatively, titles emphasizing curiosity and contrast demonstrated positive correlations with user interactions, thus validating the efficacy of these techniques. Consequently, the machine-generated titles achieved coherence on par with 65% of human-generated titles, signifying significant progress and potential for further refinement. Nevertheless, achieving socio-cultural awareness is vital to match human understanding across diverse contexts, thus presenting a critical avenue for future improvement in the methodology. Continuous advancements in AI can enhance adaptability and reduce subjectivity by promoting flexibility instead of relying solely on manual reviews. As AI gains a deeper understanding of humanity, opportunities for its application across various industries through experiential reasoning abilities emerge. This case study exemplifies the nurturing of AI's potential by refining its skills through an evolutionary process.

Exploring the Impact of Short Term Travel on Gut Microbiota and Probiotic Bacteria Mediated Stability.

Although travelers are frequently accompanied by abdominal discomfort and even diarrhea, not every trip can cause this issue. Many studies have reported that intestinal microbes play an important role in it. However, little is known about the reason for the dynamics of these intestinal microbes. Here, we delved into the effects of short-term travel on the gut microbiota of 12 healthy individuals. A total of 72 fecal samples collected before and after one-week travel, alongside non-traveling controls, underwent amplicon sequencing and a series of bioinformatic analyses. We found that travel significantly increased intra-individual gut microbiota fluctuations without diarrhea symptoms. In addition, the initial composition of the gut microbiota before travel emerged as a crucial factor in understanding these fluctuations. Travelers with stable microbiota exhibited an enrichment of specific probiotic bacteria (Agathobaculum, Faecalibacterium, Bifidobacterium, Roseburia, Lactobacillus) before travel. Another batch of data validated their predictive role in distinguishing travelers with and without the gut microbial disorder. This work provided valuable insights into understanding the relationship between gut microbiota and travel. It offered a microbiota-centric perspective and a potential avenue for interventions to preserve gut health during travel.

Effects of N levels on land productivity and N2O emissions in maize-soybean relay intercropping.

BACKGROUND: Relay intercropping of maize and soybean can improve land productivity. However, the mechanism behind N2O emissions in this practice remains unclear. A two-factor randomized block field trial was conducted to reveal the mechanism of N2O emissions in a full additive maize-soybean relay intercropping. Factor A was three cropping systems - that is, monoculture maize (Zea mays L.), monoculture soybean (Glycine max L. Merr.) and maize-soybean relay intercropping. Factor B was different N supply, containing no N, reduced N and conventional N. Differences in N2O emissions, soil properties, rhizosphere bacterial communities and yield advantage were evaluated. RESULTS: The land equivalent ratio was 1.55-2.44, and the cumulative N2O emission ( C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ ) was notably lower by 60.2% in intercropping than in monoculture, respectively. Reduced N declined C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ without penalty on the yield advantages. The relay intercropping shifted soil properties - for example, soil organic matter, total N, NH 4 + $$ {\mathrm{NH}}_4^{+} $$ and protease activity - and improved the soil microorganism community - for example, Proteobacteria and Acidobacteria. Intercropping reduced C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ by directly suppressing nirS- and amoA-regulated N2O generation during soil N cycling, or nirS- and amoA-mediated soil properties shifted to reduce C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ indirectly. Reduced N directly reduced C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ by decreasing soil N content and reducing soil microorganism activities to alleviate N2O produced in soil N cycling. CONCLUSION: Conducting a full additive maize-soybean relay intercropping with reduced nitrogen supply provides a way to alleviate N2O emissions without the penalty on the yield advantage by changing rhizosphere bacterial communities and soil N cycling. © 2024 Society of Chemical Industry.

Systematic pan-cancer analysis identified RASSF1 as an immunological and prognostic biomarker and validated in lung cancer.

Background: Ras association domain family member 1 (RASSF1) encodes the RASSF1A protein, serving as a scaffold protein situated at the intersection of a complex signalling network. Aims: To evaluate the immunological and prognostic significance of RASSF1 expression in various types of human cancers, with a specific focus on lung cancer. Methods: Differential expression analysis of RASSF1 was conducted based on data from The Cancer Genome Atlas, Genotype-Tissue Expression, and Cancer Cell Line Encyclopaedia databases. Prognostic analysis was performed using the Cox regression test and Kaplan-Meier test. Spearman's test was utilized for correlation analysis. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) gene sets were employed to enrich the associated signaling pathways. Immunohistochemical staining and quantitative real-time PCR were employed to detect protein and mRNA expression levels, respectively. Results: RASSF1 expression was significantly lower in tumour tissues than in normal tissues in most cancers, and Cox regression analysis demonstrated a significant correlation between RASSF1 expression and the prognosis of over 12 types of cancer. Specifically, high RASSF1 expression was associated with poor OS in nine cancer types, including GBMLGG (HR = 4.98, P = 1.2e-31), LGG (HR = 3.72, P = 2.5e-10), and LAML (HR = 1.48, P = 2.4e-3). Further analysis showed that RASSF1 expression was significantly correlated with immune checkpoint- and immune-related genes. Moreover, RASSF1 expression is involved in tumour microenvironment (TME), RNA modification, genomic heterogeneity, and tumour stemness. GO and KEGG analyses showed that RASSF1 was closely related to tumour immune-related pathways. Finally, RASSF1A was moderately correlated with PD-L1 (R = 0.556), and RASSF1A overexpression significantly affected the expression of several genes involved in the Th17 cell differentiation signalling pathway in lung cancer. Conclusions: RASSF1 was differentially expressed in 29 human cancers and played a critical role in tumour immunity. Thus, RASSF1 has the potential to be used as a prognostic marker and reference for achieving more precise immunotherapy, particularly in lung cancer.

Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling.

It has been shown that the high expression of human epididymis protein 4 (HE4) in most lung cancers is related to the poor prognosis of patients, but the mechanism of pathological transformation of HE4 in lung cancer is still unclear. The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma (LUAD). Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies, and through analysis of The Cancer Genome Atlas (TCGA) dataset. Frequent HE4 overexpression was demonstrated in LUAD, but not in lung squamous cell carcinoma (LUSC), indicating that HE4 can serve as a biomarker to distinguish between LUAD and LUSC. HE4 knockdown significantly inhibited cell growth, colony formation, wound healing, and invasion, and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK pathways. The first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells, while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative effects. Moreover, we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in LUAD. Our findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.

Single-cell transcriptomic analysis of the immune microenvironment in pediatric acute leukemia.

Relapse and treatment resistance pose significant challenges in the management of pediatric B cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML). The efficacy of immunotherapy in leukemia remains limited due to factors such as the immunosuppressive tumor microenvironment (TME) and lack of suitable immunotherapeutic targets. Thus, an in-depth characterization of the TME in pediatric leukemia is warranted to improve the efficacy of immunotherapy. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the TME of pediatric B-ALL and AML, focusing specifically on bone-marrow-derived T cells. Moreover, we investigated the transcriptome changes during the initiation, remission, and relapse stages of pediatric AML. Our findings revealed that specific functional expression programs correlated with fluctuations in various T cell subsets, which may be associated with AML progression and relapse. Furthermore, our analysis of cellular communication networks led to the identification of VISTA, CD244, and TIM3 as potential immunotherapeutic targets in pediatric AML. Finally, we detected elevated proportions of γδ T cells and associated functional genes in samples from pediatric patients diagnosed with B-ALL and AML, which could inform the development of novel therapeutic approaches, potentially focusing on γδ T cells.

Development and Quality Control of a Population Pharmacokinetic Model Library for Caspofungin.

BACKGROUND: Caspofungin is an echinocandin antifungal agent commonly used as the first-line therapy for invasive candidiasis, salvage therapy for invasive aspergillosis, and empirical therapy for presumed fungal infections. Pharmacokinetic (PK) variabilities and suboptimal exposure have been reported for caspofungin, increasing the risk of insufficient efficacy. OBJECTIVE: This work aimed to develop a caspofungin population pharmacokinetic (popPK) library and demonstrate its utility by assessing the probability of target attainment across diverse settings. METHODS: We established a caspofungin popPK model library following a rigorous literature review, re-implementing selected models in R with rxode2. Quality control procedures included a comparison of different studies and assessing covariate impacts. Model libraries were primarily used to perform Monte Carlo simulations to estimate target attainment and guide personalized dosing in Candida infections. RESULTS: A total of 13 models, one- or two-compartment models, were included. The most significant covariates were body size (weight and body surface area), liver function, and albumin level. The results show that children and adults showed considerable differences in pharmacokinetics. For C. albicans and C. parapsilosis, none of the populations achieved a PTA of ≥90% at their respective susceptible MIC values. In contrast, for C. glabrata, 70% of the adult studies reached a PTA of ≥90%, while all pediatric studies achieved the same PTA level. CONCLUSION: At the recommended dosage, adult patients showed notably lower exposure to caspofungin compared to pediatric patients. Considering body size, liver function, and serum albumin is crucial when determining caspofungin dosage regimens. Furthermore, further research is required to comprehensively understand the pharmacokinetics of caspofungin in pediatric patients.

Comparative efficacy of six programmed cell death Protein-1 inhibitors as first-line treatment for advanced non-small cell lung cancer: a multicenter retrospective cohort study.

The purpose of this study was to assess the comparative efficacy of six programmed cell death-1 inhibitors (nivolumab, pembrolizumab, sintilimab, tislelizumab, toripalimab, and camrelizumab) that have been used as first-line therapy for Chinese patients with advanced non-small cell lung cancer (NSCLC), which remains unclear. We determined the differences in efficacy by observing patient survival data, with the goal of informing future treatment options. Retrospective data analysis from June 2015 to April 2023 included 913 patients across six groups: nivolumab (123%, 13.5%), pembrolizumab (421%, 46.1%), sintilimab (239%, 26.1%), tislelizumab (64%, 7.0%), toripalimab (39%, 4.3%), and camrelizumab (27%, 3.0%). The median progression-free survival (PFS) for each group was 16.0, 16.1, 18.4, 16.9, 23.7, and 12.8 months, and the median overall survival (OS) was 33.7, 36.1, 32.5, not reached, 30.9 and 46.0 months for the nivolumab, sintilimab, pembrolizumab, tislelizumab, toripalimab, and camrelizumab groups, respectively. While differences existed in the objective response rates among groups (p < 0.05), there were no significant differences (all p > 0.05) in PFS or OS. The findings suggest comparable efficacy among these PD-1 inhibitors for NSCLC treatment, underscoring their collective suitability and aiding treatment decisions.

Estimation of soybean yield based on high-throughput phenotyping and machine learning.

Introduction: Soybeans are an important crop used for food, oil, and feed. However, China's soybean self-sufficiency is highly inadequate, with an annual import volume exceeding 80%. RGB cameras serve as powerful tools for estimating crop yield, and machine learning is a practical method based on various features, providing improved yield predictions. However, selecting different input parameters and models, specifically optimal features and model effects, significantly influences soybean yield prediction. Methods: This study used an RGB camera to capture soybean canopy images from both the side and top perspectives during the R6 stage (pod filling stage) for 240 soybean varieties (a natural population formed by four provinces in China: Sichuan, Yunnan, Chongqing, and Guizhou). From these images, the morphological, color, and textural features of the soybeans were extracted. Subsequently, feature selection was performed on the image parameters using a Pearson correlation coefficient threshold ≥0.5. Five machine learning methods, namely, CatBoost, LightGBM, RF, GBDT, and MLP, were employed to establish soybean yield estimation models based on the individual and combined image parameters from the two perspectives extracted from RGB images. Results: (1) GBDT is the optimal model for predicting soybean yield, with a test set R2 value of 0.82, an RMSE of 1.99 g/plant, and an MAE of 3.12%. (2) The fusion of multiangle and multitype indicators is conducive to improving soybean yield prediction accuracy. Conclusion: Therefore, this combination of parameters extracted from RGB images via machine learning has great potential for estimating soybean yield, providing a theoretical basis and technical support for accelerating the soybean breeding process.

Flexural-Mode Piezoelectric Resonators: Structure, Performance, and Emerging Applications in Physical Sensing Technology, Micropower Systems, and Biomedicine.

Piezoelectric material-based devices have garnered considerable attention from scientists and engineers due to their unique physical characteristics, resulting in numerous intriguing and practical applications. Among these, flexural-mode piezoelectric resonators (FMPRs) are progressively gaining prominence due to their compact, precise, and efficient performance in diverse applications. FMPRs, resonators that utilize one- or two-dimensional piezoelectric materials as their resonant structure, vibrate in a flexural mode. The resonant properties of the resonator directly influence its performance, making in-depth research into the resonant characteristics of FMPRs practically significant for optimizing their design and enhancing their performance. With the swift advancement of micro-nano electronic technology, the application range of FMPRs continues to broaden. These resonators, representing a domain of piezoelectric material application in micro-nanoelectromechanical systems, have found extensive use in the field of physical sensing and are starting to be used in micropower systems and biomedicine. This paper reviews the structure, working principle, resonance characteristics, applications, and future prospects of FMPRs.

Encephalitozoon hellem infection after haploidentical allogeneic hematopoietic stem cell transplantation in children: a case report.

Background: Encephalitozoon hellem (E. hellem) infection is a zoonotic disease, rarely observed in individuals, causing various clinical manifestations including diarrhea, keratoconjunctivitis, cystitis, etc. E. hellem infection after hematopoietic stem-cell transplantation (HSCT) is a rare, serious complication. Case presentation: Herein, we present a case of E. hellem infection developing during HLA-haploidentical HSCT in a 9-year-old boy who suffered from aplastic anemia. On 15 days after HSCT, the patient developed recurrent and prolonged fever, diarrhea and hematuria. It is challenging to differentiate whether the symptoms mentioned in this case are caused by graft-versus-host disease (GVHD) or a specific infection. Based on the result of metagenomic next-generation sequencing (mNGS) and clinical observation, the patient was diagnosed as E. hellem infection, and received albendazole and decreased the immunosuppressive treatment. Finally, he had recovered. Conclusion: We should pay attention to the uncommon disease caused by the E. hellem infection after HSCT, especially in cases with immune reconstitution unrecovered. Among those rare infection, mNGS can be performed for better understanding the source of infection and targeted therapy, which can benefit the patients.