Factors Associated With Decision to Use and Dosing of Sugammadex in Children: A Retrospective Cross-Sectional Observational Study.

BACKGROUND: Sugammadex was initially approved for reversal of neuromuscular blockade in adults in the United States in 2015. Limited data suggest sugammadex is widely used in pediatric anesthesia practice however the factors influencing use are not known. We explore patient, surgical, and institutional factors associated with the decision to use sugammadex versus neostigmine or no reversal, and the decision to use 2 mg/kg vs 4 mg/kg dosing. METHODS: Using data from the Multicenter Perioperative Outcomes Group (MPOG) database, an EHR-derived registry, we conducted a retrospective cross-sectional study. Eligible cases were performed between January 1, 2016 and December 31, 2020, for children 0 to 17 years at US hospitals. Cases involved general anesthesia with endotracheal intubation and administration of rocuronium or vecuronium. Using generalized linear mixed models with institution and anesthesiologist-specific random intercepts, we measured the importance of a variety of patient, clinician, institution, anesthetic, and surgical risk factors in the decision to use sugammadex versus neostigmine, and the decision to use a 2 mg/kg vs 4 mg/kg dose. We then used intraclass correlation statistics to evaluate the proportion of variance contributed by institution and anesthesiologist specifically. RESULTS: There were 97,654 eligible anesthetics across 30 institutions. Of these 47.1% received sugammadex, 43.1% received neostigmine, and 9.8% received no reversal agent. Variability in the choice to use sugammadex was attributable primarily to institution (40.4%) and attending anesthesiologist (27.1%). Factors associated with sugammadex use (compared to neostigmine) include time from first institutional use of sugammadex (odds ratio [OR], 1.08, 95% confidence interval [CI], 1.08-1.09, per month, P < .001), younger patient age groups (0-27 days OR, 2.59 [2.00-3.34], P < .001; 28 days-1 year OR, 2.72 [2.16-3.43], P < .001 vs 12-17 years), increased American Society of Anesthesiologists [ASA] physical status (ASA III: OR, 1.32 [1.23-1.42], P < .001 ASA IV OR, 1.71 [1.46-2.00], P < .001 vs ASA I), neuromuscular disease (OR, 1.14 (1.04-1.26], P = .006), cardiac surgery (OR, 1.76 [1.40-2.22], P < .001), dose of neuromuscular blockade within the hour before reversal (>2 ED95s/kg OR, 4.58 (4.14-5.07], P < .001 vs none), and shorter case duration (case duration <60 minutes OR, 2.06 [1.75-2.43], P < .001 vs >300 minutes). CONCLUSIONS: Variation in sugammadex use was primarily explained by institution and attending anesthesiologist. Patient factors associated with the decision to use sugammadex included younger age, higher doses of neuromuscular blocking agents, and increased medical complexity.

Patterns of use of symptomatic treatments for Alzheimer's disease dementia (AD).

BACKGROUND: Symptomatic treatment for Alzheimer's disease (AD) dementia could temporarily slow symptom worsening and improve the quality of life for both AD dementia patients and their caregivers. A comprehensive evaluation of symptomatic treatment patterns using recent data for newly diagnosed AD dementia has not been performed and compared across different countries. METHODS: The drug name, time to the first therapy, duration, discontinuation or switches were described in newly diagnosed AD dementia patients in two databases (a major U.S. health plan [US] and UK-Clinical Practice Research Datalink [CPRD GOLD]). This analysis included patients with newly diagnosed AD dementia in 2018-2019, who initiated symptomatic AD drug therapy, with ≥ 1 year baseline period and ≥ 1 year of follow-up. RESULTS: Over median follow-ups of 698 and 645 days, 63% and 65% of AD dementia patients used symptomatic treatments, with 34% and 77% newly initiating therapy, constituting analytic samples of 7637 patients in the US database and 4470 patients in the CPRD, respectively. The median time to the first therapy was 14 days for US and 49 days for CPRD; donepezil ranked the as most frequently used (69% vs 61%), followed by memantine (19% vs 28%) in the US database and CPRD, respectively. Median time on first therapy was 213 and 334 days, and 30% and 12% of patients proceeded to a second treatment in the US and CPRD databases, respectively. CONCLUSION: Approximately two thirds of newly diagnosed AD dementia patients utilized approved symptomatic treatment. Time on first therapy was relatively short (< 1 year) and the majority did not move to a second therapy, highlighting the need for better adherence and persistence to existing AD symptomatic therapies and the need for additional therapies to alleviate the significant burden of AD dementia.

Contribution of Comorbid Conditions to the Diagnosis of Insomnia: A Database Study in a Commercially Insured Population.

ABSTRACT: Insomnia is a common sleep disorder characterized as dissatisfaction with sleep quantity or quality resulting in distress or impairment of social, occupational, or other daily functioning. It is unknown if there are medical conditions that have strong associations with insomnia but are unrecognized in previous literature. In this cross-sectional study based on IBM Marketscan Research Databases, we measured insomnia and 78 medical conditions in patients with 2-year continuous enrollment during 2018-2019. We selected important comorbidities associated with insomnia for eight age-sex groups and built logistic regression models to measure the associations. The prevalence of diagnosed insomnia increased with age, from <0.4% in the age group 0-17 to 4%-5% in the age group ≥65. Females had a higher prevalence of insomnia than males. Anxiety and depression were two important comorbidities across all age-sex subgroups. Most odds ratios of comorbidities remained significant after adjusting for other comorbidities in regression models. We did not find any new medical conditions that had strong associations with insomnia but were unrecognized in previous literature. The findings can help physicians use comorbidities to identify patients with high risk of insomnia.

The usefulness of platelet-rich plasma to manage skin wounds: A meta-analysis.

A meta-analysis investigation to measure the usefulness of platelet-rich plasma (PRP) to manage skin wounds (SWs). A comprehensive literature inspection till February 2023 was applied and 1349 interrelated investigations were reviewed. The 22 chosen investigations enclosed animals' SWs were in the chosen investigations' starting point, 3348 of them were treated with PRP, and 2259 were control. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the usefulness of PRP to manage SWs by the dichotomous and continuous approaches and a fixed or random model. PRP significantly higher percent of decreases in open wound area (OWA) (MD, 10.07; 95% CI, 6.55-13.59, P < 0.001), and lower healing time (HT) (MD, -6.31; 95% CI, -10.69 to -1.93, P = 0.005) compared to control in animals' SWs. PRP had a significantly higher percent of decreases in OWA and lower HT compared to control in animals' SWs. However, caused of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values.

Holistic Impact Evaluation of Human Activities on the Coastal Fish Biodiversity in the Chinese Coastal Environment.

Ecological qualities and resources in coasts are threatened by various human activities, such as pollution and fishery. Impact evaluation of environmental stressors over a wide coastal stretch has been limited due to lack of efficient and standardizable biodiversity monitoring and assessment tools. Integrating environmental DNA (eDNA) and ecological traits, a holistic approach was developed to assess the impact of pollution and aquaculture on fish biodiversity in Chinese coastal areas. Taking the Yalujiang Estuary (YLJK) from the Yellow Sea and the Nan'ao Island Area (NAO) from the South China Sea as cases, the performance of the eDNA biomonitoring workflow was validated. First, the eDNA results of 22 sampling sites reached more than 85% of the asymptotes of species or ASVs in each area. A total of 115 fish species in both areas were detected and NAO was 1.8 times richer than YLJK using eDNA and the fish eDNA composition was consistent with the historical data. eDNA recovered distinct variations of fish sequence, taxonomic and functional diversity, and the corresponding trends following the offshore distance between the two areas. Fish sequence diversity was decreased primarily by estuarine pollution factors (chemical oxygen demand and zinc) in the YLJK. Compared with no breeding areas, lower fish sequence diversity was in breeding areas in the NAO. By integrating ecological traits, the eDNA approach offers promising opportunities for future fish biodiversity monitoring and assessment in national and global coastal environments.

Effect-Directed Analysis Based on the Reduced Human Transcriptome (RHT) to Identify Organic Contaminants in Source and Tap Waters along the Yangtze River.

Since a large number of contaminants are detected in source waters (SWs) and tap waters (TWs), it is important to perform a comprehensive effect evaluation and key contributor identification. A reduced human transcriptome (RHT)-based effect-directed analysis, which consisted of a concentration-dependent RHT to reveal the comprehensive effects and noteworthy pathways and systematic identification of key contributors based on the interactions between compounds and pathway effects, was developed and applied to typical SWs and TWs along the Yangtze River. By RHT, 42% more differentially expressed genes and 33% more pathways were identified in the middle and lower reaches, indicating heavier pollution. Hormone and immune pathways were prioritized based on the detection frequency, sensitivity, and removal efficiency, among which the estrogen receptor pathway was the most noteworthy. Consistent with RHT, estrogenic effects were widespread along the Yangtze River based on in vitro evaluations. Furthermore, 38 of 100 targets, 39 pathway-related suspects, and 16 estrogenic nontargets were systematically identified. Among them, diethylstilbestrol was the dominant contributor, with the estradiol equivalent (EEQ) significantly correlated with EEQwater. In addition, zearalenone and niclosamide explained up to 54% of the EEQwater. The RHT-based EDA method could support the effect evaluation, contributor identification, and risk management of micropolluted waters.

CRISPR/dCas9 for hepatic fibrosis therapy: implications and challenges.

Hepatic fibrosis is a pathological reaction of tissue damage and repair caused by various pathogenic factors acting on liver. At present, there is no effective anti-fibrotic specific therapy. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (dCas9) system is a new generation of gene editing technology. The CRISPR/dCas9 system provides a platform for studying site-specific transcriptional regulation, which has high efficiency in gene transcriptional activation for achieving robust. This system holds promise for hepatic fibrosis therapy via acting on liver fibrosis effector cells. However, there are some challenges associated with this novel technology, such as large structural variants at on-target, off-target sites, and targeted delivery efficiency. In this review, we present the potential implications and describe the challenges of CRISPR/dCas9 system that might be encountered in hepatic fibrosis therapy.

Neuromuscular Blocking Agents and Reversal Agents Among Hospitalized Children: A Cerner Database Study.

Background: Sugammadex (Bridion) was approved by the US Food and Drug Administration (FDA) in December 2015 for the reversal of neuromuscular block (NMB) induced by rocuronium and vecuronium bromide in adults undergoing surgery and approved for use in both adults and children in the European Union in 2008. Sugammadex use in children has been reported in the United States, but to what extent is not clear. Aims: The aim was to describe the utilization pattern of NMB agents and factors associated with the use of reversal agents (neostigmine and sugammadex) in US children. Methods: Cross-sectional study of children with exposure to NMB agents between 2015 and 2017 in the Cerner Health Facts® database, which is an electronic health record (EHR) database across 600 facilities in the United States. Logistic regression estimated factors associated with the use of sugammadex vs neostigmine. Results: A total of 27 094 pediatric clinical encounters were exposed to neuromuscular blocking agents (NMBAs), in which 21 845 were exposed to rocuronium (76%), vecuronium (18%), or both (6%). Among children with exposure to rocuronium and vecuronium, the use of sugammadex was 1.7% in 2016 and 7.6% in 2017. The multivariable logistic model suggested that children who were older (age 12-17 years vs 0-1 year; odds ratio [OR] 1.96; 95% confidence interval [CI], 1.36-2.83), Hispanic or Latino ethnicity and other ethnicities (vs non-Hispanic or Latino; OR 2.03 and 1.56; 95% CI, 1.55-2.67 and 1.15-2.13, respectively), in teaching facilities (OR 1.26; 95% CI, 1.00-1.59), or admitted through emergency departments (OR 1.65; 95% CI, 1.06-2.58) were independently more likely to receive sugammadex than neostigmine after controlling for other covariates. Conclusions: In Cerner Health Facts database 2015 to 2017, among children, rocuronium was more commonly used than vecuronium, and sugammadex use was observed since 2016. Sugammadex and neostigmine users varied by demographic, clinical, and site-level characteristics.

Early Monitoring Drug Resistant Mutation T790M with a Two-Dimensional Simultaneous Discrimination Nanopore Strategy.

With the aim of detecting low frequency of drug resistant mutation T790M against wild-type sequences, we reported a two-dimensional signal analysis strategy by combining a three locked nucleic acids (LNAs)-modified probe (LP15-3t) and an α-HL nanopore. The specific hybridization of the LP15-3t probe with the T790M generated unique long two-level signals, including characteristic blocking current and characteristic dwell time. Due to the significant dwell time difference (114.2-fold) and the blocking current difference ranging from 81% to 96%, this two-dimensional signal analysis strategy can simultaneously distinguish T790M sequences with a sensitivity of 0.0001% against wild-type sequences. The LOD of T790M was 0.1 pM. This high discrimination capability would have great potential in the detection of rare mutation sequences and the early monitoring of clinical outcome of NSCLC patients with TKI drug resistance.

Circ-SLC8A1 regulates osteoporosis through blocking the inhibitory effect of miR-516b-5p on AKAP2 expression.

BACKGROUND: Osteoporosis is a disease characterized by bone loss, imbalance of bone metabolism and destruction of trabecular microarchitecture. Circular RNAs (circRNAs) have been revealed as important biological regulators in human diseases. The expression characteristics and mechanism of circRNAs in osteoporosis are unclear. METHODS: The binding sites of miR-516b-5p on circ-SLC8A1 and AKAP2 mRNA were predicted using circAtlas (http://circatlas.biols.ac.cn) and miRDB (http://mirdb.org). Target sites of miR-516b-5p on circ-SLC8A1 and AKAP2 mRNA were confirmed by a dual luciferase assay. The relationship between miR-516b-5p and AKAP2 was determined by a quantitative reverse transcriptase-polymerase chain reaction. Alizarin red S staining and alkaline phosphatase staining were used to observe the level of osteogenic differentiation after transfection. RESULTS: The first six circRNAs captured from the 30 circRNAs with highest expression in the bone marrow were examined in a mouse model of osteoporosis and the expression of circ-SLC8A1 was found to be significantly reduced in osteoporosis. Circ-SLC8A1 negatively regulated the expression of miR-516b-5p. Overexpression of circ-SLC8A1 blocked the inhibition of AKAP2 by miR-516b-5p. CONCLUSIONS: Circ-SLC8A1 blocks the inhibitory effect of miR-516b-5p on the downstream target gene AKAP2 and promotes osteoporosis. The findings of the present might help to provide a new strategy for the treatment of osteoporosis.

Genipin inhibits the scleral expression of miR-29 and MMP2 and promotes COL1A1 expression in myopic eyes of guinea pigs.

PURPOSE: High myopia can lead to blindness. Genipin is a collagen cross-linking agent that may be used to treat myopia. However, the mechanism of action of genipin for the treatment of myopia is unclear. This study investigated the effect of genipin on the scleral expression of the miR-29 cluster, matrix metalloproteinase 2 (MMP2), and collagen alpha1 chain of type I (COL1A1) in a guinea pig model of myopia. METHODS: The model of myopia was established by treating guinea pigs with a - 8D lens on both eyes for 21 days, and eyes with a refractive error of - 6D or greater were included. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to examine the mRNA and protein expression, respectively. A dual-luciferase assay was used to determine the direct targeting of the miR-29 cluster on the 3'-untranslated region (UTR) of the COL1A1 gene. RESULTS: The scleral expression of miR-29a, miR-29b, and miR-29c as well as MMP2 was significantly increased, and the scleral expression of COL1A1 was significantly decreased in the myopia group. Genipin treatment reversed these effects in myopic eyes. The dual-luciferase assay showed that the luciferase activities were significantly decreased in human embryonic kidney (HEK) cells transfected with miR-29a and miR-29b, but not miR-29c, compared with those transfected with control miRNAs. CONCLUSIONS: Genipin inhibits the scleral expression of the miR-29 cluster and MMP2 and promotes COL1A1 expression in a guinea pig model of myopia. Thus, genipin may promote COL1A1 expression by reducing the expression of the miR-29 cluster.

Pediatric exposure to opioid and sedation medications during terminal hospitalizations in the United States, 2007-2011.

OBJECTIVE: To describe the use of opioids and sedatives to pediatric patients dying in the hospital in the 2 weeks preceding death. STUDY DESIGN: We conducted a retrospective study on opioid and sedation medication exposure among children who die in hospitals in the US by using large administrative data sources. We described patterns of exposure to these medications for deceased inpatients (<21 years of age) between 2007 and 2011 (n = 37,459) and factors associated with the exposure. Multivariable logistic regression models were used to estimate the ORs. RESULTS: Overall, 74% patients were exposed to opioids or sedatives in the 14 days before death. Among patients with 6 or more hospital days before death, the daily exposure rate ranged from 73% (the sixth day before death) to 89% (the day of death). The most commonly used medications were fentanyl (52%), midazolam (44%), and morphine (40%). Older age (ORs 1.6-3.7), black race (ORs 0.8), longer hospital stay (ORs 6.6-9.3), receiving medical interventions (including mechanical ventilation, surgery, and stay in the intensive care unit, ORs 1.7-2.6), having comorbidities (ORs 1.7-2.4), and being hospitalized in children's hospitals (ORs 4.0-4.5) were associated with exposure of opioid and sedation medication on adjusted analysis. CONCLUSION: Although most pediatric patients terminally hospitalized are exposed to opioid and sedation medication, some patients do not receive such medications before death. Given that patient and hospital characteristics were associated with opioid/sedative exposure, these findings suggest areas of potential quality improvement and further research.

Pulse wave velocity and cognitive function in older adults.

Arterial stiffness may be associated with cognitive function. In this study, pulse wave velocity (PWV) was measured from the carotid to femoral (CF-PWV) and from the carotid to radial (CR-PWV) with the Complior SP System. Cognitive function was measured by 6 tests of executive function, psychomotor speed, memory, and language fluency. A total of 1433 participants were included (mean age 75 y, 43% men). Adjusting for age, sex, education, pulse rate, hemoglobin A1C, high-density lipoprotein cholesterol, hypertension, cardiovascular disease history, smoking, drinking, and depression symptoms, a CF-PWV>12 m/s was associated with a lower Mini-Mental State Examination score (coefficient: -0.31, SE: 0.11, P=0.005), fewer words recalled on Auditory Verbal Learning Test (coefficient: -1.10, SE: 0.43, P=0.01), and lower score on the composite cognition score (coefficient: -0.10, SE: 0.05, P=0.04) and marginally significantly associated with longer time to complete Trail Making Test-part B (coefficient: 6.30, SE: 3.41, P=0.06), CF-PWV was not associated with Trail Making Test-part A, Digit Symbol Substation Test, or Verbal Fluency Test. No associations were found between CR-PWV and cognitive performance measures. Higher large artery stiffness was associated with worse cognitive function, and longitudinal studies are needed to confirm these associations.

Time trends of antidepressant drug prescriptions in men versus women in a geographically defined US population.

The aim of this work was to study time trends of antidepressant drug (AD) prescriptions in a geographically defined US population between 2005 and 2011 for men and women separately. Using the Rochester Epidemiology Project medical records-linkage system, we identified all Olmsted County, MN residents who received AD outpatient prescriptions between 2005 and 2011 (7 years). We calculated the annual age- and sex-specific prevalence over 7 years and used generalized estimating equation models to test for time trends. The prevalence of subjects receiving at least one AD prescription was approximately two times higher in women than in men consistently across the 7 years of the study. The standardized annual prevalence increased from 10.8 % in 2005 to 14.4 % in 2011 overall, from 7.0 % in 2005 to 9.9 % in 2011 for men, and from 14.4 % in 2005 to 18.6 % in 2011 for women. The absolute percent increase was greater in women (4.2 vs. 2.9 %; standardized); however, the relative percent increase was greater in men (41.4 vs. 29.2 %; standardized). The relative percent increase was greater in the age group 65+ years for both men and women. AD prescriptions are increasing over time, especially in the elderly. Women receive more AD prescriptions than men. However, the relative increase in AD prescriptions over time is greater in men than women.

Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation.

BACKGROUND: The pediatric complex chronic conditions (CCC) classification system, developed in 2000, requires revision to accommodate the International Classification of Disease 10th Revision (ICD-10). To update the CCC classification system, we incorporated ICD-9 diagnostic codes that had been either omitted or incorrectly specified in the original system, and then translated between ICD-9 and ICD-10 using General Equivalence Mappings (GEMs). We further reviewed all codes in the ICD-9 and ICD-10 systems to include both diagnostic and procedural codes indicative of technology dependence or organ transplantation. We applied the provisional CCC version 2 (v2) system to death certificate information and 2 databases of health utilization, reviewed the resulting CCC classifications, and corrected any misclassifications. Finally, we evaluated performance of the CCC v2 system by assessing: 1) the stability of the system between ICD-9 and ICD-10 codes using data which included both ICD-9 codes and ICD-10 codes; 2) the year-to-year stability before and after ICD-10 implementation; and 3) the proportions of patients classified as having a CCC in both the v1 and v2 systems. RESULTS: The CCC v2 classification system consists of diagnostic and procedural codes that incorporate a new neonatal CCC category as well as domains of complexity arising from technology dependence or organ transplantation. CCC v2 demonstrated close comparability between ICD-9 and ICD-10 and did not detect significant discontinuity in temporal trends of death in the United States. Compared to the original system, CCC v2 resulted in a 1.0% absolute (10% relative) increase in the number of patients identified as having a CCC in national hospitalization dataset, and a 0.4% absolute (24% relative) increase in a national emergency department dataset. CONCLUSIONS: The updated CCC v2 system is comprehensive and multidimensional, and provides a necessary update to accommodate widespread implementation of ICD-10.

Norditerpenoids from Flickingeria fimbriata and their inhibitory activities on nitric oxide and tumor necrosis factor-α production in mouse macrophages.

Bioassay-guided fractionation of the ethanolic extract of the leaves of Flickingeria flimbriata led to the isolation of two new degraded diterpenoids 1 and 2, a new ent-pimarane type diterpenoid 3, and four known steroids 4-7. The structures of 1-3 were elucidated by spectroscopic analysis, and their absolute configurations were determined by chemical methods, TDDFT quantum chemical calculations of ECD spectra, and CD exiton chirality method. Compounds 1 and 2, named flickinflimilins A and B, possess a rare 15,16-dinor-ent-pimarane skeleton. Compounds 1-7 were screened for the inhibitory activity against lipopolysaccharide (LPS)-induced NO and TNF-α production in RAW264.7 cells. Compounds 1-3 exhibited potent inhibitory activities, with IC50 values of less than 10 µM.

The therapeutic effectiveness of artificial intelligence-based chatbots in alleviation of depressive and anxiety symptoms in short-course treatments: A systematic review and meta-analysis.

BACKGROUND: The emergence of artificial intelligence-based chatbot has revolutionized the field of clinical psychology and psychotherapy, granting individuals unprecedented access to professional assistance, overcoming time constraints and geographical limitations with cost-effective convenience. However, despite its potential, there has been a noticeable gap in the literature regarding their effectiveness in addressing common mental health issues like depression and anxiety. This meta-analysis aims to evaluate the efficacy of AI-based chatbots in treating these conditions. METHODS: A systematic search was executed across multiple databases, including PubMed, Cochrane Library, Web of Science, PsycINFO, and Embase on April 4th, 2024. The effect size of treatment efficacy was calculated using the standardized mean difference (Hedge's g). Quality assessment measures were implemented to ensure trial's quality. RESULTS: In our analysis of 18 randomized controlled trials involving 3477 participants, we observed noteworthy improvements in depression (g = -0.26, 95 % CI = -0.34, -0.17) and anxiety (g = -0.19, 95 % CI = -0.29, -0.09) symptoms. The most significant benefits were evident after 8 weeks of treatment. However, at the three-month follow-up, no substantial effects were detected for either condition. LIMITATIONS: Several limitations should be considered. These include the lack of diversity in the study populations, variations in chatbot design, and the use of different psychotherapeutic approaches. These factors may limit the generalizability of our findings. CONCLUSION: This meta-analysis highlights the promising role of AI-based chatbot interventions in alleviating depressive and anxiety symptoms among adults. Our results indicate that these interventions can yield substantial improvements over a relatively brief treatment period.

Evaluating eDNA and eRNA metabarcoding for aquatic biodiversity assessment: From bacteria to vertebrates.

The monitoring and management of aquatic ecosystems depend on precise estimates of biodiversity. Metabarcoding analyses of environmental nucleic acids (eNAs), including environmental DNA (eDNA) and environmental RNA (eRNA), have garnered attention for their cost-effective and non-invasive biomonitoring capabilities. However, the accuracy of biodiversity estimates obtained through eNAs can vary among different organismal groups. Here we evaluate the performance of eDNA and eRNA metabarcoding across nine organismal groups, ranging from bacteria to terrestrial vertebrates, in three cross-sections of the Yangtze River, China. We observe robust complementarity between eDNA and eRNA data. The relative detectability of eNAs was notably influenced by major taxonomic groups and organismal sizes, with eDNA providing more robust signals for larger organisms. Both eDNA and eRNA exhibited similar cross-sectional and longitudinal patterns. However, the detectability of larger organisms declined in eRNA metabarcoding, possibly due to differential RNA release and decay among different organismal groups or sizes. While underscoring the potential of eDNA and eRNA in large river biomonitoring, we emphasize the need for differential interpretation of eDNA versus eRNA data. This highlights the importance of careful method selection and interpretation in biomonitoring studies.

[Spatial-temporal Distribution and Source Analysis of Polycyclic Aromatic Hydrocarbons in the Sediments of Poyang Lake].

The concentrations, spatial-temporal distribution, and influencing factors of 16 polycyclic aromatic hydrocarbons (PAHs) in the sediments of Poyang Lake were studied, and a quantitative source analysis of PAHs in different areas of the lake was conducted. PAHs were widespread within the sediments. The concentrations of ∑16PAHs in the surface sediments of all sites ranged from 203 to 2 318 µg·kg-1. The concentrations of PAHs in the surface sediments of the lake body were higher than those in the surface sediments of the inlet rivers. The ratio of PAHs in Poyang Lake was 4 rings > 5 rings > 6 rings > 3 rings > 2 rings; the composition of 4-ring PAHs was dominant, and its content accounted for 86.11% of ∑16PAHs. The 2- and 3-ring and some 4-ring PAHs, including Flua and Pyr, were more susceptible to SOM, and the 4 through 6-ring PAHs were more susceptible to ORP and heavy metals and other environmental factors. Spatially, the higher concentration of ∑16PAHs occurred in the area of the lake adjacent to Duchang County and Poyang County, where the terrain was relatively closed, and the water exchange with the surrounding area was less than that in other sections, which was not conducive to the migration, transformation, and degradation of pollutants. In the temporal distribution, the changes in PAHs concentration level and the development of GDP in Jiangxi Province showed high consistency, and the influence of economic development and human activities might have been the main reason for the increasing PAHs concentration level. The main sources of PAHs in surface sediments of Poyang Lake included petroleum pollution and oil and coal and biomass combustion sources, and there were some spatial differences in PAHs sources in different regions. This study can provide a reference for PAHs pollution in surface sediments of Poyang Lake, which is important for the ecological environmental protection and management of Poyang Lake.

Prevalence and prognosis of hypoxia-inducible factor-2α (HIF-2α) pathway gene mutations across advanced solid tumors.

INTRODUCTION: Hypoxia-inducible factor-2α (HIF-2α) modulates the hypoxic response pathway in tumors; however, mutations in pathways (including SDHA, SDHB, SDHC, SDHD, FH, and VHL genes) that are suspected to activate HIF-2α are poorly understood, with limited understanding of the prevalence and clinical prognosis. METHODS: This retrospective observational study used a de-identified nationwide (US-based) clinico-genomic database (CGDB) across 15 available tumor types. RESULTS: Among the 9467 adult patients with advanced/metastatic solid tumors included in the analysis, any mutation at the above-mentioned six genes was observed in 1.8% (95% CI: 1.5-2.1) of patients. The mutation prevalence ranged from 0.05% of SDHD to 0.93% of VHL. When further stratified by tumor type, the prevalence of gene mutation in each tumor type was well below 1%, except for VHL with 44% in renal cell carcinomas (RCC). Excluding RCC, the prevalence of any HIF-2α gene mutations in the study population was 0.9% (95% CI: 0.8-1.2). The median overall survival (OS) from 1 and 2 L therapy among patients with any HIF-2α gene mutation was 14.5 (95% CI: 11.5-24.2) and 9.3 (95% CI: 6.0-18.1) months, respectively, compared with 13.4 (95% CI: 12.9-13.9) and 9.8 (95% CI: 9.3-10.4) months among patients without HIF-2α gene mutations. DISCUSSION AND CONCLUSIONS: The prevalence of HIF-2α related gene mutations was generally low (<1%) across the 15 solid tumor types, except for VHL in RCC. No significant association between HIF-2α gene mutation status and OS was identified among patients evaluated in this study.