In vivo effects of cell seeding technique in an ex vivo regional gene therapy model for bone regeneration.

When delivering cells on a scaffold to treat a bone defect, the cell seeding technique determines the number and distribution of cells within a scaffold, however the optimal technique has not been established. This study investigated if human adipose-derived stem cells (ASCs) transduced with a lentiviral vector to overexpress bone morphogenetic protein 2 (BMP-2) and loaded on a scaffold using dynamic orbital shaker could reduce the total cell dose required to heal a critical sized bone defect when compared with static seeding. Human ASCs were loaded onto a collagen/biphasic ceramic scaffold using static loading and dynamic orbital shaker techniques, compared with our labs standard loading technique, and implanted into femoral defects of nude rats. Both a low dose and standard dose of transduced cells were evaluated. Outcomes investigated included BMP-2 production, radiographic healing, micro-computerized tomography, histologic assessment, and biomechanical torsional testing. BMP-2 production was higher in the orbital shaker cohort compared with the static seeding cohort. No statistically significant differences were noted in radiographic, histomorphometric, and biomechanical outcomes between the low-dose static and dynamic seeding groups, however the standard-dose static seeding cohort had superior biomechanical properties. The standard-dose 5 million cell dose standard loading cohort had superior maximum torque and torsional stiffness on biomechanical testing. The use of orbital shaker technique was labor intensive and did not provide equivalent biomechanical results with the use of fewer cells.

Zeolite application mitigates NH3 and N2O emissions from pig slurry-applied field and improves nitrogen use efficiency in Italian ryegrass-maize crop rotation system for forage production.

The present study aimed to assess the efficiency of zeolite in mitigating the nitrogen (N) losses through ammonia (NH3) and nitrous oxide (N2O) emissions from pig slurry (PS) applied to Italian ryegrass (IRG)-maize fields under a crop rotation system and the consequent effect on nitrogen use efficiency (NUE) for forage production. PS was applied at rates of 150 and 200 kg N ha-1 for the IRG and maize growing seasons, respectively, with or without zeolite. Soil mineral N content and NH3 and N2O emissions were measured periodically throughout the year-round cultivation of IRG and maize. Forage yield and nutritional composition were also analyzed at the harvest time of each crop. The PS with/without zeolite application effects were interpreted by comparison with those obtained for the negative control (no-N fertilization). Soil ammonium (NH4+) content in the PS-applied plots sharply increased within the first week, then progressively decreased in both the IRG and maize growing seasons. Soil NH4+ contents in the zeolite-amended plots were higher compared to the treatment without zeolite except for the first 1 or 2 weeks after PS application when soil nitrate (NO3-) contents significantly decreased. The increase in soil NH4+ content as affected by zeolite application was more distinct in the maize growing season than in the IRG growing season. NH3 emission was predominant at the early 2 weeks after PS application. Zeolite application reduced the cumulative emission of NH3 from PS by 16.7% and 24.4% and that of N2O by 15.6% and 31.5% in the IRG growing and maize growing seasons, respectively. NUE for dry matter (DM) and total digestible nutrients (TDN) production significantly improved in annual yield basis of the IRG-maize cropping. Zeolite application in PS-applied field may represent effective management in mitigating N losses through odorous NH3 and greenhouse gas (N2O) emissions, thereby improving NUE forage production.

Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea, 2010-2018.

BACKGROUND: Inflammatory bowel disease (IBD) was previously regarded as a Western disease; however, its incidence is increasing in the East. The epidemiology of IBD in Asia differs significantly from the patterns in the West. AIM: To comprehensively investigate the epidemiology of IBD in South Korea, including its incidence, prevalence, medication trends, and outcomes. METHODS: We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases (RIDs), operated by the National Health Insurance Service of South Korea. Patients with IBD were identified based on the International Classification of Diseases, Tenth Revision, and RID diagnostic codes for Crohn's disease (CD) and ulcerative colitis (UC) from 2010 to 2018. RESULTS: In total, 14498 and 31409 patients were newly diagnosed with CD and UC, respectively, between 2010 and 2018. The annual average incidence of CD was 3.11 cases per 105 person-years, and that of UC was 6.74 cases per 105 person-years. Since 2014, the incidence rate of CD has been stable, while that of UC has steadily increased, shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in 2018. The CD and UC prevalence increased consistently over the study period; the use of 5-aminosalicylates and corticosteroids gradually decreased, while that of immunomodulators and biologics steadily increased in both CD and UC. The clinical outcomes of IBD, such as hospitalization and surgery, decreased during the study period. CONCLUSION: The CD incidence has been stable since 2014, but that of UC has increased with a shift to a younger age at peak incidence between 2010 and 2018. IBD clinical outcomes improved over time, with increased use of immunomodulators and biologics.

Overcoming BRAF and CDK4/6 inhibitor resistance by inhibiting MAP3K3-dependent protection against YAP lysosomal degradation.

Transcriptional programs governed by YAP play key roles in conferring resistance to various molecular-targeted anticancer agents. Strategies aimed at inhibiting YAP activity have garnered substantial interest as a means to overcome drug resistance. However, despite extensive research into the canonical Hippo-YAP pathway, few clinical agents are currently available to counteract YAP-associated drug resistance. Here, we present a novel mechanism of YAP stability regulation by MAP3K3 that is independent of Hippo kinases. Furthermore, we identified MAP3K3 as a target for overcoming anticancer drug resistance. Depletion of MAP3K3 led to a substantial reduction in the YAP protein level in melanoma and breast cancer cells. Mass spectrometry analysis revealed that MAP3K3 phosphorylates YAP at serine 405. This MAP3K3-mediated phosphorylation event hindered the binding of the E3 ubiquitin ligase FBXW7 to YAP, thereby preventing its p62-mediated lysosomal degradation. Robust YAP activation was observed in CDK4/6 inhibitor-resistant luminal breast cancer cells. Knockdown or pharmacological inhibition of MAP3K3 effectively suppressed YAP activity and restored CDK4/6 inhibitor sensitivity. Similarly, elevated MAP3K3 expression supported the prosurvival activity of YAP in BRAF inhibitor-resistant melanoma cells. Inhibition of MAP3K3 decreased YAP-dependent cell proliferation and successfully restored BRAF inhibitor sensitivity. In conclusion, our study reveals a previously unrecognized mechanism for the regulation of YAP stability, suggesting MAP3K3 inhibition as a promising strategy for overcoming resistance to CDK4/6 and BRAF inhibitors in cancer treatment.

Polarization-selective four-wave mixing in a degenerate multi-level system.

This paper describes the first observation of polarization-selective four-wave mixing signals in conventional coupling-probe spectroscopy, specifically, saturation absorption spectroscopy in 85Rb atoms. The four-wave mixing signal is induced by two counter-propagating laser beams in a degenerate multi-level atomic system, involving the F g = 3 → F e = 2 , 3 , and 4 transitions of the 85Rb D2 line. Consequently, the four-wave mixing signals copropagating along the probe beam induce polarization rotation of a linearly polarized probe beam. To distinguish these four-wave mixing signals from the resulting probe beam, we detect the polarization components orthogonal to the polarization direction of the input probe beam, depending on the linear polarization angles between the probe and coupling beams. The experimental findings demonstrate excellent agreement with theoretical results.

Predicting adequate segmental lordosis correction in lumbar spinal stenosis patients undergoing oblique lumbar interbody fusion: a focus on the discontinuous segment.

PURPOSE: To identify the factors associated with a correction of the segmental angle (SA) with a total change greater than 10° in each level following minimally invasive oblique lumbar interbody fusion (MIS-OLIF). METHODS: Patients with lumbar spinal stenosis who underwent single- or two-level MIS-OLIF were reviewed. Segments with adequate correction of the SA >10° after MIS-OLIF in immediate postoperative radiograph were categorized as discontinuous segments (D segments), whereas those without such improvement were assigned as continuous segments (C segments). Clinical and radiological parameters were compared, and multivariate logistic regression analysis was performed to identify factors associated with SA correction >10° after MIS-OLIF. RESULTS: Of 211 segments included, 38 segments (18.0%) were classified as D segments. Compared with C segments, D segments demonstrated a significantly smaller preoperative SA (mean ± standard deviation [SD], - 1.1° ± 6.7° vs. 6.6° ± 6.3°, p < 0.001), larger change of SA (mean ± SD, 13.5° ± 3.4° vs. 3.1° ± 3.9°, p < 0.001), and a higher rate of presence of facet effusion (76.3% vs. 48.6%, p = 0.002). Logistic regression revealed preoperative SA (odds ratio (OR) [95% confidence interval (CI)]:0.733 [0.639-0.840], p < 0.001) and facet effusion (OR [95% CI]:14.054 [1.758-112.377], p = 0.027) as significant predictors for >10° SA correction after MIS-OLIF. CONCLUSION: Preoperative kyphotic SA and facet effusion can predict SA correction >10° following MIS-OLIF. For patients with lordotic SA and no preoperative facet effusion, supplemental procedures, such as anterior column release or posterior osteotomy, should be prepared for additional lumbar lordosis correction required for remnant global sagittal imbalance after MIS-OLIF.

Drinkable in situ-forming tough hydrogels for gastrointestinal therapeutics.

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing.

Comparison of influence of intercalation and substitution of Cu on electrical and thermoelectric transport properties of InSe alloys.

Layered post-transition-metal chalcogenides, such as InSe, In4Se3, SnSe, and SnSe2, have recently been investigated as semiconducting electronic materials and thermoelectric materials owing to their adjustable electrical transport properties either by doping or alloying. Herein, the influence of intercalation doping and substitutional doping of Cu in layered InSe alloys on electrical and thermoelectric transport properties was investigated and compared by synthesizing varied compositions of CuxInSe and In1-yCuySe. It was found that Cu was intercalated in CuxInSe samples (x = 0.01 and 0.02) and behaved as an electron donor, resulting in an increase in the electron concentration and a decrease in the activation energy. Therefore, the power factor of CuxInSe samples was increased compared to that of InSe. In contrast, the substituted Cu in the In site of In1-yCuySe samples (y = 0.01 and 0.02) acted as an acceptor, and the power factor decreased owing to a decrease in the electron concentration and activation energy. Moreover, a decrease in thermal conductivity was seen for CuxInSe and In1-yCuySe samples due to increased phonon scattering after the addition of Cu. Consequently, an enhanced thermoelectric figure of merit (zT) was only observed for intercalated CuxInSe samples due to the increased power factor and decreased thermal conductivity, while substituted In1-yCuySe samples only show degraded zT. A maximum zT value of 0.062 was observed for the CuxInSe (x = 0.02) sample at 700 K, which showed a 77% enhancement compared to that of InSe.

Partial Molar Solvation Volume of the Hydrated Electron Simulated Via DFT.

Different simulation models of the hydrated electron produce different solvation structures, but it has been challenging to determine which simulated solvation structure, if any, is the most comparable to experiment. In a recent work, Neupane et al. [J. Phys. Chem. B 2023, 127, 5941-5947] showed using Kirkwood-Buff theory that the partial molar volume of the hydrated electron, which is known experimentally, can be readily computed from an integral over the simulated electron-water radial distribution function. This provides a sensitive way to directly compare the hydration structure of different simulation models of the hydrated electron with experiment. Here, we compute the partial molar volume of an ab-initio-simulated hydrated electron model based on density-functional theory (DFT) with a hybrid functional at different simulated system sizes. We find that the partial molar volume of the DFT-simulated hydrated electron is not converged with respect to the system size for simulations with up to 128 waters. We show that even at the largest simulation sizes, the partial molar volume of DFT-simulated hydrated electrons is underestimated by a factor of 2 with respect to experiment, and at the standard 64-water size commonly used in the literature, DFT-based simulations underestimate the experimental solvation volume by a factor of ∼3.5. An extrapolation to larger box sizes does predict the experimental partial molar volume correctly; however, larger system sizes than those explored here are currently intractable without the use of machine-learned potentials. These results bring into question what aspects of the predicted hydrated electron radial distribution function, as calculated by DFT-based simulations with the PBEh-D3 functional, deviate from the true solvation structure.

Incidence and survival rates of primary cutaneous malignancies in Korea, 1999-2019: A nationwide population-based study.

Primary cutaneous malignancies are among the most commonly diagnosed types of cancer worldwide. We aimed to examine the incidence and 5-year survival rates of all types of primary cutaneous malignancies in the Korean population. Data from the Korean Nationwide Cancer Registry from 1999 to 2019 were analyzed. The crude incidence rates, age-standardized incidence rates, and 5-year relative survival rates of each type of skin cancer were calculated. A total of 89 965 patients were diagnosed with primary cutaneous malignancies, which was a 7-fold increase from 1999 to 2019. The age-standardized incidence rates increased 3.4-fold in basal cell carcinoma (3.7/100 000 person-years), 2.0-fold in squamous cell carcinoma (1.6/100 000 person-years), 12.0-fold in Bowen disease (1.2/100 000 person-years), and 1.8-fold in malignant melanoma (0.7/10 000 person-years) in 2019. Average annual percentage changes in age-standardized incidence rates were statistically significant in basal cell carcinoma (15.8%), Bowen disease (5.8%), squamous cell carcinoma (5.1%), malignant melanoma (1.2%), melanoma in situ (1.1%), dermatofibrosarcoma protuberans (1.2%), mycosis fungoides (0.5%), primary cutaneous CD30+ T-cell proliferations (0.5%), adnexal and skin appendage carcinoma (0.4%), extramammary Paget's disease (0.2%), and Merkel cell carcinoma (0.2%). The 5-year relative survival rates were the highest in basal cell carcinoma (103.3%), followed by dermatofibrosarcoma protuberans (99.7%) and mycosis fungoides (96.6%), and lowest in angiosarcoma (24.7%). The 5-year relative survival rates steadily increased in extramammary Paget's disease (23.6%), cutaneous B-cell lymphoma (21.3%), mycosis fungoides (20.2%), extranodal NK/T-cell lymphoma, nasal type (18.1%), and malignant melanoma (16.1%) from 1996-2000 to 2015-2019. Most primary cutaneous malignancies have increased in incidence and survival rates in the Korean population, but to varying extents depending on the type of skin cancer.

Reduction of Upper Gastrointestinal Bleeding Risk With Proton Pump Inhibitor Therapy in Asian Patients With Atrial Fibrillation Receiving Direct Oral Anticoagulant: A Nationwide Population-based Cohort Study.

BACKGROUND & AIMS: In patients with atrial fibrillation (AF) receiving direct oral anticoagulant (DOAC), upper gastrointestinal bleeding (UGIB) is a serious complication. There are limited data on the benefit of preventive proton pump inhibitor (PPI) use to reduce the risk of UGIB in DOAC users. METHODS: We included patients with AF receiving DOAC from 2015 to 2020 based on the Korean Health Insurance Review and Assessment database. The propensity score (PS) weighting method was used to compare patients with PPI use and those without PPI use. The primary outcome was hospitalization for UGIB. Weighted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were evaluated using the Cox proportional hazards regression model. RESULTS: A total of 165,624 patients were included (mean age: 72.2 ± 10.8 years; mean CHA2DS2-VASc score: 4.3 ± 1.8; mean HAS-BLED score: 3.3 ± 1.2). Among them, 99,868 and 65,756 were in the non-PPI group and PPI group, respectively. During a median follow-up of 1.5 years, the PPI group was associated with lower risks of hospitalization for UGIB and UGIB requiring red blood cell transfusion than non-PPI group (weighted HR, 0.825; 95% CI, 0.761-0.894 and 0.798; 95% CI, 0.717-0.887, respectively, both P < .001). The benefits of PPI on the risk of hospitalization for UGIB were greater in those with older age (≥75 years), higher HAS-BLED score (≥3), prior GIB history, and concomitant use of antiplatelet agent (all P-for-interaction < .1). Low-dose PPI was consistently associated with a lower risk of significant UGIB by 43.6-49.3% (P < .001). CONCLUSIONS: In this large Asian cohort of patients with AF on DOAC, PPI co-therapy is beneficial for reducing the risk of hospitalization for UGIB, particularly in high-risk patients.

An additively manufactured model for preclinical testing of cervical devices.

Purpose: Composite models have become commonplace for the assessment of fixation and stability of total joint replacements; however, there are no comparable models for the cervical spine to evaluate fixation. The goal of this study was to create the framework for a tunable non-homogeneous model of cervical vertebral body by identifying the relationships between strength, in-fill density, and lattice structure and creating a final architectural framework for specific strengths to be applied to the model. Methods: The range of material properties for cervical spine were identified from literature. Using additive manufacturing software, rectangular prints with three lattice structures, gyroid, triangle, zig-zag, and a range of in-fill densities were 3D-printed. The compressive and shear strengths for all combinations were calculated in the axial and coronal planes. Eleven unique vertebral regions were selected to represent the distribution of density. Each bone density was converted to strength and subsequently correlated to the lattice structure and in-fill density with the desired material properties. Finally, a complete cervical vertebra model was 3D-printed to ensure sufficient print quality. Results: Materials testing identified a relationship between in-fill densities and strength for all lattice structures. The axial compressive strength of the gyroid specimens ranged from 1.5 MPa at 10% infill to 31.3 MPa at 100% infill and the triangle structure ranged from 2.7 MPa at 10% infill to 58.4 MPa at 100% infill. Based on these results, a cervical vertebra model was created utilizing cervical cancellous strength values and the corresponding in-fill density and lattice structure combination. This model was then printed with 11 different in-fill densities ranging from 33% gyroid to 84% triangle to ensure successful integration of the non-homogeneous in-fill densities and lattice structures. Conclusions: The findings from this study introduced a framework for using additive manufacturing to create a tunable, customizable biomimetic model of a cervical vertebra.

Cumulative exposure to impaired fasting glucose and gastrointestinal cancer risk: A nationwide cohort study.

BACKGROUND: Impaired fasting glucose (IFG) is associated with the risk of various cancers, but the cumulative effect of IFG on gastrointestinal cancer risk remains unclear. This study evaluated the association between the cumulative exposure to IFG and gastrointestinal cancer risk. METHODS: The authors extracted data from the Korean National Health Insurance Service and health examination data sets. Among individuals ≥40 years old who were free of diabetes or cancer, 1,430,054 who underwent national health examinations over 4 consecutive years from 2009 to 2012 were selected and followed up until gastrointestinal cancer diagnosis, death, or December 31, 2019. The IFG exposure score (range, 0-4) was based on the number of IFG diagnoses over 4 years. RESULTS: The median follow-up duration was 6.4 years. Consistent normoglycemia for 4 years was found in 44.3% of the population, whereas 5.0% had persistent IFG and 50.7% had intermittent IFG. Compared to the group with an IFG exposure score of 0, groups with IFG exposure scores of 1, 2, 3, and 4 had a 5%, 8%, 9%, and 12% increased risk of gastrointestinal cancer, respectively (score 1: adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 1.01-1.08; score 2: aHR, 1.08; 95% CI, 1.04-1.12; score 3: aHR, 1.09; 95% CI, 1.05-1.14; score 4: aHR, 1.12; 95% CI, 1.06-1.19). Persistent IFG exposure was also associated with higher risks of individual cancer types (colorectum, stomach, pancreas, biliary tract, and esophagus). CONCLUSIONS: Cumulative exposure to IFG is associated with an increased risk of developing gastrointestinal cancer, in a dose-dependent manner. PLAIN LANGUAGE SUMMARY: Hyperglycemia, including both diabetes and prediabetes, has been associated with an increased risk of various cancers. However, the cumulative effect of impaired fasting glucose on the risk of developing gastrointestinal cancer remains unclear. A frequent diagnosis of impaired fasting glucose was dose-dependently associated with a higher risk of developing overall gastrointestinal cancer. Furthermore, risks of individual cancer types increased with persistent impaired fasting glucose. Early detection of hyperglycemia and strict glycemic control can lower the risk of gastrointestinal cancer by reducing hyperglycemic burden. Additionally, for some individuals, lifestyle changes such as managing metabolic syndrome or abstaining from alcohol may also be helpful.

Multi-Modal Multi-Array Electrochemical and Optical Sensor Suite for a Biological CubeSat Payload.

CubeSats have emerged as cost-effective platforms for biological research in low Earth orbit (LEO). However, they have traditionally been limited to optical absorbance sensors for studying microbial growth. This work has made improvements to the sensing capabilities of these small satellites by incorporating electrochemical ion-selective pH and pNa sensors with optical absorbance sensors to enrich biological experimentation and greatly expand the capabilities of these payloads. We have designed, built, and tested a multi-modal multi-array electrochemical-optical sensor module and its ancillary systems, including a fluidic card and an on-board payload computer with custom firmware. Laboratory tests showed that the module could endure high flow rates (1 mL/min) without leakage, and the 27-well, 81-electrode sensor card accurately detected pH (71.0 mV/pH), sodium ion concentration (75.2 mV/pNa), and absorbance (0.067 AU), with the sensors demonstrating precise linear responses (R2 ≈ 0.99) in various test solutions. The successful development and integration of this technology conclude that CubeSat bio-payloads are now poised for more complex and detailed investigations of biological phenomena in space, marking a significant enhancement of small-satellite research capabilities.

The crosstalk between PTEN-induced kinase 1-mediated mitophagy and the inflammasome in the pathogenesis of alopecia areata.

Alopecia areata (AA) is a T-cell-mediated autoimmune disease that causes chronic, relapsing hair loss; however, its precise pathogenesis remains to be elucidated. Recent studies have provided compelling evidence of crosstalk between inflammasomes and mitophagy-a process that contributes to the removal of damaged mitochondria. Our previous studies showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome is important for eliciting and progressing inflammation in AA. In this study, we detected mitochondrial DNA damage in AA-affected scalp tissues and IFNγ and poly(I:C) treated outer root sheath (ORS) cells. In addition, IFNγ and poly(I:C) treatment increased mitochondrial reactive oxygen species (ROS) levels in ORS cells. Moreover, we showed that mitophagy induction alleviates IFNγ and poly(I:C)-induced NLRP3 inflammasome activation in ORS cells. Lastly, PTEN-induced kinase 1 (PINK1) knockdown increased NLRP3 inflammasome activation, indicating that PINK1-mediated mitophagy plays a critical role in NLRP3 inflammasome activation in ORS cells. This study supports previous studies showing that oxidative stress disrupts immune privilege status and promotes autoimmunity in AA. The results emphasize the significance of crosstalk between mitophagy and inflammasomes in the pathogenesis of AA. Finally, mitophagy factors regulating mitochondrial dysfunction and inhibiting inflammasome activation could be novel therapeutic targets for AA.

Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease.

Human embryonic stem cell (hESC)-derived midbrain dopaminergic (mDA) cell transplantation is a promising therapeutic strategy for Parkinson's disease (PD). Here, we present the derivation of high-purity mDA progenitors from clinical-grade hESCs on a large scale under rigorous good manufacturing practice (GMP) conditions. We also assessed the toxicity, biodistribution, and tumorigenicity of these cells in immunodeficient rats in good laboratory practice (GLP)-compliant facilities. Various doses of mDA progenitors were transplanted into hemi-parkinsonian rats, and a significant dose-dependent behavioral improvement was observed with a minimal effective dose range of 5,000-10,000 mDA progenitor cells. These results provided insights into determining a low cell dosage (3.15 million cells) for human clinical trials. Based on these results, approval for a phase 1/2a clinical trial for PD cell therapy was obtained from the Ministry of Food and Drug Safety in Korea, and a clinical trial for treating patients with PD has commenced.

Machine learning-based water quality prediction using octennial in-situ Daphnia magna biological early warning system data.

Biological early warning system (BEWS) has been globally used for surface water quality monitoring. Despite its extensive use, BEWS has exhibited limitations, including difficulties in biological interpretation and low alarm reproducibility. This study addressed these issues by applying machine learning (ML) models to eight years of in-situ BEWS data for Daphnia magna. Six ML models were adopted to predict contamination alarms from Daphnia behavioral parameters. The light gradient boosting machine model demonstrated the most significant improvement in predicting alarms from Daphnia behaviors. Compared with the traditional BEWS alarm index, the ML model enhanced the precision and recall by 29.50% and 43.41%, respectively. The speed distribution index and swimming speed were significant parameters for predicting water quality warnings. The nonlinear relationships between the monitored Daphnia behaviors and water physicochemical water quality parameters (i.e., flow rate, Chlorophyll-a concentration, water temperature, and conductivity) were identified by ML models for simulating Daphnia behavior based on the water contaminants. These findings suggest that ML models have the potential to establish a robust framework for advancing the predictive capabilities of BEWS, providing a promising avenue for real-time and accurate assessment of water quality. Thereby, it can contribute to more proactive and effective water quality management strategies.

Association between dental diseases and oral hygiene care and the risk of vertebral fracture: a nationwide cohort study.

Periodontal disease and increased missing teeth were associated with incident vertebral fractures. In contrast, professional dental cleaning and frequent tooth brushing, was associated with a lower risk of vertebral fracture. Better oral hygiene care attenuated the risk associated with dental diseases. PURPOSE: To investigate the association between oral health and the risk of vertebral fractures. METHODS: We included 2,532,253 individuals aged ≥40 years who underwent the Korean National Health Insurance Service health examinations in 2008 and followed up until December 31, 2017. We performed multivariable Cox proportional hazard regression analyses to evaluate the association between dental diseases and oral hygiene care and the risk of vertebral fractures. RESULTS: Over the 9.3-year median follow-up, 1.46% (n = 36,857) experienced vertebral fractures. Individuals with dental diseases had a higher risk of vertebral fracture than those without (hazard ratio [HR] 1.04, 95% confidence interval [CI]: 1.02-1.07 for periodontal diseases; 1.02, 1.00-1.05 for dental caries; 1.12, 1.05-1.20 for ≥15 missing teeth). Good oral hygiene care was associated with a lower vertebral fracture risk (HR 0.89, 95% CI: 0.86-0.91 for ≥1 time/year [vs. <1 time/year] of professional dental cleaning; 0.90, 0.87-0.93 for ≥2 times/day [vs. 0-1 time/day] of toothbrushing). The combined dental diseases was significantly associated with an increased vertebral fracture risk, whereas combined oral hygiene care was associated with further risk reduction. Better oral hygiene care reduced vertebral fracture risk associated with dental diseases (all P <0.001). CONCLUSION: Periodontal disease, dental caries, and an increased number of missing teeth were independently associated with higher risks for vertebral fractures. Conversely, improved oral hygiene care, such as personal dental cleaning and frequent tooth brushing, may modify vertebral fracture risks associated with dental disease.

The Fate of Pre-Existing L5-S1 Degeneration following Oblique Lumbar Interbody Fusion of L4-L5 and Above.

BACKGROUND: Previous studies have identified various risk factors for adjacent segment disease (ASD) at the L5-S1 level after fusion surgery, including preoperative sagittal imbalance, longer fusion, and preoperative disc degeneration. However, only a few studies have explored the risk factors for ASD at the L5-S1 level after oblique lumbar interbody fusion (OLIF) at the L4-L5 level and above. This study aimed to identify the risk factors for symptomatic ASD at the L5-S1 level in patients with pre-existing degeneration after OLIF at L4-L5 and above. METHODS: We retrospectively reviewed the data of patients who underwent OLIF at L4-L5 and above, with a minimum follow-up period of 2 years. Patients with central stenosis or Lee grade 2 or 3 foraminal stenosis at L5-S1 preoperatively were excluded. Patients were divided into ASD and non-ASD groups based on the occurrence of new-onset L5 or S1 radicular pain requiring epidural steroid injection (ESI). The clinical and radiological factors were analyzed. Logistic regression was used to identify the risk factors for ASD of L5-S1. RESULTS: A total of 191 patients with a mean age ± standard deviation of 68.6 ± 8.3 years were included. Thirty-four (21.7%) patients underwent ESI at the L5 root after OLIF. In the logistic regression analyses, severe disc degeneration (OR (95% confidence interval (CI)): 2.65 (1.16-6.09)), the presence of facet effusion (OR (95% CI): 2.55 (1.05-6.23)), and severe paraspinal muscle fatty degeneration (OR (95% CI): 4.47 (1.53-13.05)) were significant risk factors for ASD in L5-S1. CONCLUSIONS: In this study, the presence of facet effusion, severe disc degeneration, and severe paraspinal muscle fatty degeneration at the L5-S1 level were associated with the development of ASD at L5-S1 following OLIF at L4-L5 and above. For patients with these conditions, surgeons could consider including L5-S1 in the fusion when considering OLIF at the L4-L5 level and above.