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Wastewater-based epidemiology (WBE) has the potential to produce reliable, efficient, and non-invasive measures of current psychoactive drug use. The aim of this study was to assess the feasibility and validity of using WBE to estimate current cocaine use among university students at a residential campus. We analyzed wastewater samples from four locations at a residential university campus during spring semester of 2021, testing for cocaine metabolites in addition to control comparison substances (acetaminophen and caffeine). We simultaneously administered a confidential self-report survey of recent substance use behaviors to a randomized sample of undergraduate students at this university. Self-reported survey estimates of cocaine use and point estimates of cocaine use derived from wastewater-based epidemiology are similar, but the survey is imprecise with a wide CI, and agreement is sensitive to key WBE assumptions; thus, results are consistent but not conclusive. The self-report survey results indicated 0.13% of respondents were regular cocaine users, which is equivalent to the estimate of 0.12% of students using cocaine as measured through WBE. This prevalence is also in line with the 0.14% National American College Health Association (NACHA) survey during the same semester. WBE shows promise as a complementary approach for estimating current cocaine use among students on a residential campus; with current data the WBE point estimate is similar to the survey point estimate, but uncertainty in both measures (especially the survey) requires further research.

A precise, scalable, and computationally efficient mathematical framework is proposed for region-wide autonomous electric vehicle (AEV) fleet management, sizing and infrastructure planning for urban ride-hailing services. A comprehensive techno-economic analysis in New York City is conducted not only to calculate the societal costs but also to quantify the environmental and health benefits resulting from reduced emissions. The results reveal that strategic fleet management can reduce fleet size and unnecessary cruising mileage by up to 40% and 70%, respectively. This alleviates traffic congestion, saves travel time, and further reduces fleet sizes. Besides, neither large-battery-size AEVs nor high-power charging infrastructure is necessary to achieve efficient service. This effectively alleviates financial and operational burdens on fleet operators and power systems. Moreover, the reduced travel time and emissions resulting from efficient fleet autonomy create an economic value that exceeds the total capital investment and operational costs of fleet services.

Objective Delayed fracture healing increases the suffering of patients. An in-depth investigation of the pathogenesis of delayed fracture healing may offer new direction for the prevention and treatment. Methods The study included 63 normal healing tibial fractures and 58 delayed healing tibial fractures patients. Long non-coding RNA (lncRNA)TRPM2-AS, microRNA-545-3p (miR-545-3p), bone morphogenetic protein 2 ( Bmp2 ) mRNA and osteogenic differentiation markers, including runt-related transcription factor 2 ( Runx2 ), osteocalcin ( Ocn ), and alkaline phosphatase ( Alp ) mRNA expression were determined by Real-time quantitative reverse transcription-polymerase chain reaction in serum and MC3T3-E1 cells. The prediction potential of TRPM2-AS in delayed healing fracture patients was verified by receiver operating characteristic curves. The binding relationship of TRPM2-AS/miR-545-3p/ Bmp2 was evaluated by dual luciferase reporter gene assay. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry. Results TRPM2-AS was remarkably down-regulated in patients with delayed fracture healing and could better predict the fracture healing status. TRPM2-AS downregulation inhibited osteogenic markers mRNA expression, restrained proliferation, and promoted apoptosis of MC3T3-E1 cells ( p  < 0.05). In delayed fracture healing, miR-545-3p was dramatically up-regulated and was negatively regulated by TRPM2-AS. Reducing miR-545-3p eliminate the negative effect of TRPM2-AS down-regulation on osteoblast proliferation and differentiation ( p  < 0.05). miR-545-3p targets Bmp2 , which plays a positive role in osteoblast differentiation ( p  < 0.05). Conclusion This study found that TRPM2-AS has the potential to be a diagnostic marker for delayed fracture healing and revealed that the TRPM2-AS/miR-545-3p/ Bmp2 axis affects fracture healing by regulating osteoblast.

Background Open distal tibial fractures pose significant challenges regarding treatment options and patient outcomes. This retrospective single-centre study aimed to compare the stability, clinical outcomes, complications, and financial implications of two surgical interventions, namely the external locking plate and the combined frame external fixator, to manage open distal tibial fractures. Methods Forty-four patients with distal open tibial (metaphyseal extraarticular) fractures treated between 2020 and 2022 were selected and formed into two main groups, Group A and Group B. Group A (19 patients) are patients that underwent treatment using the external locking plate technique, while Group B (25 patients) received the combined frame external fixator approach. Age, gender, inpatient stay, re-operation rates, complications, functional recovery (measured by the Johner-Wrush score), pain ratings (measured by the Visual Analogue Scale [VAS]), and cost analyses were evaluated for each group. Statistical analyses using SPSS were conducted to compare the outcomes between the two groups. Results The research found significant variations in clinical outcomes, complications, and cost consequences between Group A and Group B. Group A had fewer hospitalisation periods (23.687.74) than Group B (33.5619.47). Re-operation rates were also considerably lower in Group A (26.3%) than in Group B (48%), owing to a greater prevalence of pin-tract infections and subsequent pin loosening in the combination frame external fixator group. The estimated cost of both techniques was recorded and analysed with the locking average of 26,619.69 ± 9,602.352 and the combined frame average of 39,095.64 ± 20,070.077. Conclusion This study suggests that although the two approaches effectively manage open distal tibia fractures, the locking compression plate approach (Group A) has an advantage in treating open distal tibia fractures. Shorter hospitalisation times, reduced re-operation rates, and fewer complications will benefit patients, healthcare systems, and budget allocation. Group A's functional recovery results demonstrate the locking plate technique's ability to improve recovery and patient quality of life. According to the cost analysis, the locking plate technique's economic viability and cost-effectiveness may optimise healthcare resources for open distal tibia fractures. These findings might improve patient outcomes and inform evidence-based orthopaedic surgery.

The liquid–liquid phase separation (LLPS) of proteins has been found ubiquitously in eukaryotic cells, and is critical in the control of many biological processes by forming a temporary condensed phase with different bimolecular components. TDP-43 is recruited to stress granules in cells and is the main component of TDP-43 granules and proteinaceous amyloid inclusions in patients with amyotrophic lateral sclerosis (ALS). TDP-43 low complexity domain (LCD) is able to de-mix in solution, forming the protein condensed droplets, and amyloid aggregates would form from the droplets after incubation. The molecular interactions regulating TDP-43 LCD LLPS were investigated at the protein fusion equilibrium stage, when the droplets stopped growing after incubation. We found the molecules in the droplet were still liquid-like, but with enhanced intermolecular helix–helix interactions. The protein would only start to aggregate after a lag time and aggregate slower than at the condition when the protein does not phase separately into the droplets, or the molecules have a reduced intermolecular helix–helix interaction. In the protein condensed droplets, a structural transition intermediate toward protein aggregation was discovered involving a decrease in the intermolecular helix–helix interaction and a reduction in the helicity. Our results therefore indicate that different intermolecular interactions drive LLPS and fibril formation. The discovery that TDP-43 LCD aggregation was faster through the pathway without the first protein phase separation supports that LLPS and the intermolecular helical interaction could help maintain the stability of TDP-43 LCD.

•The fusion rate after OLIF was 94.4% at 2-year follow-up, with 86% satisfaction rate.•Cystic lesion may increase back pain in the early postoperative period.•Cage subsidence significantly increased the risk of non-union.•Cage subsidence was a significant risk factor for positive cyst formation.•Positive cyst sign was potentially an indirect predictor of non-union. To determine longitudinal effects of changes in endplate cystic lesions on oblique lumbar interbody fusion (OLIF), the relationship between bone healing and endplate cystic lesion changes, and clinical significance of cyst formation. A total of 107 segments in 67 patients who underwent OLIF between January 2013 and July 2016 were examined in this retrospective study. Using computed tomography, radiographic examinations of endplate cystic lesion, positive or negative cyst formation, cage subsidence, and fusion status were performed. Clinical outcomes were measured using visual analogue scale (VAS) pain scores, Oswestry disability index (ODI), and modified Macnab criteria. Outcomes were compared with preoperatively and postoperatively. A logistic regression analysis was performed to evaluate the relationship between measurements for endplate cysts. The fusion rate after OLIF was 94.4% at 2-year follow-up, with 86% of cases reporting satisfactory outcome (based on modified Macnab criteria). A significantly higher (P <  0.01) VAS score for back pain was observed in the cystic lesion group than non-cystic lesion group at 6-month follow-up. Cage subsidence significantly increased the risk of non-union (odds ratio [OR]: 17.24; 95% confidence interval [CI]: 1.67–178.09). Positive cyst sign was a significant risk factor for cage subsidence (OR: 8.52; 95% CI: 2.73–26.62) while cage subsidence was also a significant risk factor for positive cyst formation (OR: 8.37; 95% CI: 2.71–25.89). Cystic lesion may increase back pain in the early postoperative period. However, the preoperative cystic lesion does not aggravate a positive cyst formation or affect the final clinical result. Positive cyst formation was a significant risk factor for cage subsidence. In addition, cage subsidence was a significant predictor of non-union. Thus, the authors can speculate that positive cyst sign was potentially an indirect predictor of non-union.

Sediment pore-water dissolved organic matter (DOM) in two North Dakota prairie pothole lakes was quantified by dissolved organic carbon analysis (DOC) and its composition was characterized as a function of sediment depth for molecular weight distribution (MWD), molar absorptivity at 280 nm (ε280), and fluorescence properties. Fluorescence excitation emission matrices were further analyzed by creating a Parallel Factor Analysis (PARAFAC) model specific to sedimentary pore-water DOM. The range of absolute pore-water DOC concentrations (∼ 26–183 mg C L−1) greatly exceeded abundances reported for other wetlands and generally increased with depth. Significant changes occurred in e280 and fluorescence seasonally. Prairie pothole pore-water DOM is primarily allochthonous in nature and three ‘humic-like’ components explained ∼ 90% of total sample fluorescence, while a single ‘non-humic’ component was responsible for the remaining 10%. The contribution of the non-humic component, however, was more significant in the top 7 cm of sediment in samples collected in early autumn and is presumably derived from algal precursor material produced by primary production in the water column over the summer. The PARAFAC results corroborate ε280 and MWD changes in pore-water DOM composition over the growing season. This dynamic process could affect the type of DOM available for biogeochemical processes seasonally.

Cage subsidence frequently complicates lumbar fusion procedures, including lateral lumbar interbody fusion (LLIF), potentially leading to recurrent pain, impaired fusion, and accelerated degeneration of adjacent segments. A critical factor influencing cage subsidence is the selection of material. Polyetheretherketone (PEEK) and three-dimensional printed titanium (3D-Ti) cages are commonly used in LLIF procedures, each offering distinct advantages. However, these materials possess inherent property differences that may translate into divergent settling rates. To contribute to this discourse and offer insights, this systematic review and meta-analysis aims to compare the rates of cage subsidence between 3D-Ti and PEEK cages in LLIF. A meticulous systematic search that employs distinct MeSH terms was conducted in major electronic databases (MEDLINE, PubMed, Embase, Scopus, Web of Science, and Cochrane) up to December 20, 2023. The quality of inclusion was measured using the Newcastle-Ottawa Scale (NOS) for non-randomized trials. The primary outcome measure was cage subsidence, while the secondary outcome involved evaluating subsidence within each treatment segment using the Marchi classification. The review included 265 patients (441 segments) from three studies. All with NOS ratings exceeding 5 stars. In the analysis, 189 segments (42.9%) underwent LLIF with 3D-Ti cages, while 252 segments (57.1%) participated in LLIF with PEEK cages. Overall, the cage subsidence rate was significantly lower with 3D-Ti compared to PEEK (  < 0.00001, OR = 0.25; 95% CI 0.14 to 0.44). Specifically, the 3D-Ti group exhibited a markedly lower subsidence rate, categorized by grade I, II, and III, compared to the PEEK group (  < 0.05). Furthermore, the incidence of severe subsidence was significantly reduced in the 3D-Ti group compared to the PEEK group (  = 0.0004, OR = 0.17; 95% CI 0.07 to 0.46). The study concludes that the subsidence rate associated with 3D-Ti cages in LLIF is notably lower than that observed with PEEK cages, underscoring the potential advantages of 3D-Ti cages in mitigating cage subsidence.

Background Surgical treatment alone is not effective in addressing delayed fracture healing (DFH). This study nvestigates the molecular mechanism underlying fracture healing to identify improved therapeutic strategies. Methods Serum samples were collected from 76 normal fracture healing (NFH) and 70 DFH patients. RT-qPCR was performed to determine LINC00662, miR-330-3p, and PTEN mRNA expression in serum and Human Bone marrow mesenchymal stem cells (HBMSCs). The diagnostic potential of LINC00662 and miR-330-3p for DFH patients was evaluated via ROC analysis. Binding sites were predicted using bioinformatic databases and validated by dual-luciferase reporter assays. HBMSCs proliferation, apoptosis and osteogenic differentiation were analyzed using CCK-8, flow cytometry, andosteogenesis-related gene expression assays. Results LINC00662 was upregulated and miR-330-3p downregulated in DFH, and the two combined could efficiently diagnose DFH. LINC00662 knockdown promoted runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) mRNA expression, enhanced HBMSCs proliferation, and suppressed apoptosis. miR-330-3p inhibition reversed these effect. As a target of miR-330-3p, PTEN downregulation ameliorated the negative effects of miR-330-3p downregulation on HBMSCs. Conclusion LINC00662 and miR-330-3p synergistically could improve the diagnostic efficiency of DFH. LINC00662 impedes fracture healing by suppressing osteogenic differentiation and proliferation of HBMSCs while promoting apoptosis in HBMSCs via the miR-330-3p/PTEN axis.

Background Masquelet membrane induction technology is one of the treatment strategies for large bone defect (LBD). However, the angiogenesis ability of induced membrane decreases with time and autologous bone grafting is associated with donor site morbidity. This study investigates if the PRP-FG-nHA/PA66 scaffold can be used as a spacer instead of PMMA to improve the angiogenesis ability of induced membrane and reduce the amount of autologous bone graft. Methods Platelet rich plasma (PRP) was prepared and PRP-FG-nHA/PA66 scaffold was synthesized and observed. The sustained release of VEGFA and porosity of the scaffold were analyzed. We established a femur LBD model in male SD rats. 55 rats were randomly divided into four groups depending on the spacer filled in the defect area. “Defect only” group ( n  = 10), “PMMA” group ( n  = 15), “PRP-nHA/PA66” group ( n  = 15) and “PRP-FG-nHA/PA66” group ( n  = 15 ). At 6 weeks, the spacers were removed and the defects were grafted. The induced membrane and bone were collected and stained. The bone formation was detected by micro-CT and the callus union was scored on a three point system. Results The PRP-FG-nHA/PA66 scaffold was porosity and could maintain a high concentration of VEGFA after 30 days of preparation. The induced membrane in PRP-FG-nHA/PA66 group was thinner than PMMA, but the vessel density was higher.The weight of autogenous bone grafted in PRP-FG-nHA/PA66 group was significantly smaller than that of PMMA group. In PRP-FG-nHA/PA66 group, the bone defect was morphologically repaired. Conclusion The study showed that PRP-FG-nHA/PA66 scaffold can significantly reduce the amount of autologous bone graft, and can achieve similar bone defect repair effect as PMMA. Our findings provide some reference and theoretical support for the treatment of large segmental bone defects in humans.