Small non-coding RNAome changes during human chondrocyte senescence as potential epigenetic targets in age-related osteoarthritis.

Chondrocyte senescence is a decisive component of age-related osteoarthritis, however, the function of small noncoding RNAs (sncRNAs) in chondrocyte senescence remains underexplored. Human hip joint cartilage chondrocytes were cultivated up to passage 4 to induce senescence. RNA samples were extracted and then analyzed using small RNA sequencing and qPCR. ß-galactosidase staining was used to detect the effect of sncRNA on chondrocyte aging. Results of small RNA sequencing showed that 279 miRNAs, 136 snoRNAs, 30 snRNAs, 102 piRNAs, and 5 rasiRNAs were differentially expressed in senescent chondrocytes. The differential expression of 150 sncRNAs was further validated by qPCR. Transfection of sncRNAs and ß-galactosidase staining were also performed to further revealed that hsa-miR-135b-5p, SNORA80B-201, and RNU5E-1-201 have the function to restrain chondrocyte senescence, while has-piR-019102 has the function to promote chondrocyte senescence. Our data suggest that sncRNAs have therapeutic potential as novel epigenetic targets in age-related osteoarthritis.

Predicting spatiotemporally-resolved mean air temperature over Sweden from satellite data using an ensemble model.

Mapping of air temperature (Ta) at high spatiotemporal resolution is critical to reducing exposure assessment errors in epidemiological studies on the health effects of air temperature. In this study, we applied a three-stage ensemble model to estimate daily mean Ta from satellite-based land surface temperature (Ts) over Sweden during 2001-2019 at a high spatial resolution of 1 × 1 km2. The ensemble model incorporated four base models, including a generalized additive model (GAM), a generalized additive mixed model (GAMM), and two machine learning models (random forest [RF] and extreme gradient boosting [XGBoost]), and allowed the weights for each model to vary over space, with the best-performing model for each grid cell assigned the highest weight. Various spatial predictors were included as adjustment variables in all the base models, including land cover type, normalized difference vegetation index (NDVI), and elevation. The ensemble model showed high performance with an overall R2 of 0.98 and a root mean square error of 1.38 °C in the ten-fold cross-validation, and outperformed each of the four base models. Although each base model performed well, the two machine learning models (RF [R2 = 0.97], XGBoost [R2 = 0.98]) had better performance than the two regression models (GAM [R2 = 0.95], GAMM [R2 = 0.96]). In the machine learning models, Ts was the dominant predictor of Ta, followed by day of year, NDVI, latitude, elevation, and longitude. The highly spatiotemporally-resolved Ta can improve temperature exposure assessment in future epidemiological studies.

Associations between short-term ambient ozone exposure and cause-specific mortality in rural and urban areas of Jiangsu, China.

Most previous studies on the acute health effects of ozone are limited to urban areas, largely due to the paucity of air pollutant measurements in rural areas. We here estimated the county-specific daily maximum 8-h average ozone concentration in Jiangsu Province, China during 2015-2018, using a recently developed spatiotemporal machine learning model at a spatial resolution of 0.1° × 0.1° (∼11 × 11 km). Counties were equally divided into urban and rural groups based on the median of the percentage of urban residents across Jiangsu counties obtained from the National Population Census in 2010. We first conducted time-series analyses to estimate the county-specific effect of ozone using generalized linear models, then pooled the effect estimates by random-effects modeling. A 10 µg/m3 increase in the 4-day moving average (lag 0-3) of ambient ozone exposure was associated with increases of 0.66% (95% confidence interval [CI] 0.36%-0.95%) in daily nonaccidental mortality in rural areas and 0.42% in urban areas (95% CI, 0.27%-0.56%). Short-term ambient ozone exposure was associated with an increased risk of mortality caused by chronic obstructive pulmonary disease, hypertension, ischemic heart disease, and stroke. Our finding suggests that both urban and rural residents suffer adverse health effects from short-term ozone exposure.

Particulate matter pollution and risk of outpatient visits for psychological diseases in Nanjing, China.

Exposure to air pollution has been associated with increased risk for a range of adverse mental health conditions. Less is known about whether air pollution is also associated with increases in the utilization of mental health services, especially outpatient mental health service utilization. This study aimed to examine the association between the number of daily outpatient visits at the psychological disease departments of two major hospitals (PSYC) and daily average concentrations of PM2.5 and PM10 in a heavily polluted city in China, Nanjing, from 2013/7/1 to 2019/2/28, using generalized additive models with a quasi-Poisson regression. Results showed that each 10 µg/m3 increase in PM2.5 concentration on lag0 day was associated with a 0.40% increase (95% CI: 0.07-0.72) in PSYC visits, and each 10 µg/m3 increase in PM10 concentration on the same day a 0.31% increase (95% CI: 0.09-0.54) in PSYC visits. Exposure-response curves suggested linear relationships between PM concentration and daily PSYC outpatient visits, without evidence of a threshold. Associations remained positive, but were non-significant, with adjustment for co-pollutants, SO2, NO2 and CO. Significantly larger effects were found for older and male participants, vs. their counterparts. These findings add to the growing literature linking air pollution to mental health service utilization, demonstrating the critical need for both air pollution mitigation measures and increased capacity of the mental health system in China.

Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal.

The clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8+ cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy.

Open Source Remote Monitoring of Research Lasers.

An open source remote monitoring system is designed and built to address the needs of researchers to provide basic illuminated visual indication of laser operation for university research laboratories that are equipped with multiple types of high-powered lasers and have limited financial resources. The 3D printed remote monitoring system selectively monitors either the total current running through a laser or a TTL shutter signal to wirelessly indicate at the laboratory entrances that a laser is in use. Several lasers can be monitored in a single room and each room entrance can have its own wireless laser activity indicator. The wireless feature eliminates the expense of in-wall wiring for the system. An emergency shut off switch is included as an optional attachment. This article describes the design of the readily deployed open source laser monitoring system, including how it was built and tested for integration into a microscopy research laboratory.

Surface functionalization of titanium with zinc/strontium-doped titanium dioxide microporous coating via microarc oxidation.

Deficient osseointegration and implant-related infections are pivotal issues for the long-term clinical success of titanium (Ti) implants. Zinc (Zn) and strontium (Sr) serve dual functions by promoting osteogenesis and inhibiting bone destruction, and Zn has good antibacterial activity. As such, this study examined the preparation of a Zn/Sr-doped titanium dioxide microporous coating (MT-Zn/Sr) on a Ti surface using microarc oxidation (MAO), with Zn and Sr evenly distributed throughout the coating. In vitro, the coating could promote the adhesion, proliferation, differentiation and mineralization of osteoblasts, showing good biological activity. Antibacterial testing demonstrated the good antibacterial activity of the coating, as it inhibited the proliferation of Staphylococcus. In vivo, MT-Zn/Sr promoted early osseointegration between the Ti substrate and the bone tissue. This work is expected to provide a new method for improving the biological activity of Ti implants and thus has important theoretical significance and great clinical prospects.

Canadian Wildfire Smoke and Asthma Syndrome Emergency Department Visits in New York City.

This study examines the association between the Canadian wildfires that occurred in summer 2023 with emergency department visits for asthma symptoms in New York City.

Single-Level Rigid Fixation Combined with Coflex: A Biomechanical Study.

BACKGROUND: The purpose of this biomechanical in vitro study was to compare the kinematics and intradiscal pressure achieved with 2 methods: L4-L5 pedicle screw-rod fixation (PSRF) with an upper L3-L4 Coflex device and L4-L5 PSRF alone. The results were used to characterize the biomechanics of the topping-off operation with a Coflex device for the lumbar motion segment adjacent to single-level rigid fixation. MATERIAL/METHODS: Six human cadaveric spine specimens were biomechanically tested in vitro (6 males, 0 females). The 3-dimensional specimen motion in response to applied loads during flexibility tests was determined. Loads were applied along anatomic axes to induce flexion-extension, lateral bending, and axial rotation. All specimens were first studied with intact lumbar motion segments, then with L4-L5 PSRF alone, and finally with L4-L5 PSRF with an upper L3-L4 Coflex device. A non-paired comparison of the 3 configurations under 3 different conditions was made. RESULTS: PSRF, with or without a Coflex device, significantly increased the range of motion (ROM) in the upper adjacent motion segments in all directions of loading. The intradiscal pressure (IDP) changed slightly. A correlation analysis showed that the ROM and IDP are significantly positively correlated. The application of the upper motion segment of the Coflex device provided greater stability in all directions of motion than did PSRF alone, particularly for extension (p<0.05), while use of a Coflex device did not significantly decrease the IDP compared with PSRF alone (p>0.05). CONCLUSIONS: These results suggest that L4-L5 PSRF with an L3-L4 Coflex device is more stable than L4-L5 PSRF alone. PSRF with an upper Coflex device is a promising alternative to PSRF alone. Based on these biomechanical tests, it might be considered a protective method to prevent adjacent segment degeneration (ASD), although some limitations with this in vitro study must be addressed in the future.

Short-Term Exposure to Fine Particulate Matter and Nitrogen Dioxide and Mortality in 4 Countries.

Importance: The association between short-term exposure to air pollution and mortality has been widely documented worldwide; however, few studies have applied causal modeling approaches to account for unmeasured confounders that vary across time and space. Objective: To estimate the association between short-term changes in fine particulate matter (PM2.5) and nitrogen dioxide (NO2) concentrations and changes in daily all-cause mortality rates using a causal modeling approach. Design, Setting, and Participants: This cross-sectional study used air pollution and mortality data from Jiangsu, China; California; central-southern Italy; and Germany with interactive fixed-effects models to control for both measured and unmeasured spatiotemporal confounders. A total of 8 963 352 deaths in these 4 regions from January 1, 2015, to December 31, 2019, were included in the study. Data were analyzed from June 1, 2021, to October 30, 2023. Exposure: Day-to-day changes in county- or municipality-level mean PM2.5 and NO2 concentrations. Main Outcomes and Measures: Day-to-day changes in county- or municipality-level all-cause mortality rates. Results: Among the 8 963 352 deaths in the 4 study regions, a 10-µg/m3 increase in daily PM2.5 concentration was associated with an increase in daily all-cause deaths per 100 000 people of 0.01 (95% CI, 0.001-0.01) in Jiangsu, 0.03 (95% CI, 0.004-0.05) in California, 0.10 (95% CI, 0.07-0.14) in central-southern Italy, and 0.04 (95% CI, 0.02- 0.05) in Germany. The corresponding increases in mortality rates for a 10-µg/m3 increase in NO2 concentration were 0.04 (95% CI, 0.03-0.05) in Jiangsu, 0.03 (95% CI, 0.01-0.04) in California, 0.10 (95% CI, 0.05-0.15) in central-southern Italy, and 0.05 (95% CI, 0.04-0.06) in Germany. Significant effect modifications by age were observed in all regions, by sex in Germany (eg, 0.05 [95% CI, 0.03-0.06] for females in the single-pollutant model of PM2.5), and by urbanicity in Jiangsu (0.07 [95% CI, 0.04-0.10] for rural counties in the 2-pollutant model of NO2). Conclusions and Relevance: The findings of this cross-sectional study contribute to the growing body of evidence that increases in short-term exposures to PM2.5 and NO2 may be associated with increases in all-cause mortality rates. The interactive fixed-effects model, which controls for unmeasured spatial and temporal confounders, including unmeasured time-varying confounders in different spatial units, can be used to estimate associations between changes in short-term exposure to air pollution and changes in health outcomes.

Long-term exposure to wildfire smoke PM2.5 and mortality in the contiguous United States.

Despite the growing evidence on the health effects of short-term exposure to wildfire smoke fine particles (PM2.5), the impacts of long-term wildfire smoke PM2.5 exposure remain unclear. We investigated the association between long-term exposure to wildfire smoke PM2.5 and all-cause mortality and mortality from a wide range of specific causes in all 3,108 counties in the contiguous U.S., 2007-2020. Monthly county-level mortality data were collected from the National Center for Health Statistics. Wildfire smoke PM2.5 concentration was derived from a 10×10 km2 resolution spatiotemporal model. Controlling for non-smoke PM2.5, air temperature, and unmeasured spatial and temporal confounders, we found a non-linear association between 12-month moving average concentration of smoke PM2.5 and monthly all-cause mortality rate. Relative to a month with the long-term smoke PM2.5 exposure below 0.1 µg/m3, all-cause mortality increased by 0.40-1.54 and 3.65 deaths per 100,000 people per month when the 12-month moving average of PM2.5 concentration was of 0.1-5 and 5+ µg/m3, respectively. Cardiovascular, ischemic heart disease, digestive, endocrine, diabetes, mental, suicide, and chronic kidney disease mortality were all found to be associated with long-term wildfire smoke PM2.5 exposure. Smoke PM2.5 contributed to approximately 30,180 all-cause deaths/year (95% CI: 21,449, 38,910) in the contiguous U.S. Higher smoke PM2.5-related increases in mortality rates were found for people aged 65 above and racial minority populations. Positive interaction effects with extreme heat were also observed. Our study identified the detrimental effects of long-term exposure to wildfire smoke PM2.5 on a wide range of mortality outcomes, underscoring the need for public health actions and communication to prepare communities and individuals to mitigate smoke exposure.

Air pollution changes due to COVID-19 lockdowns and attributable mortality changes in four countries.

COVID-19 lockdowns reduced nitrogen dioxide (NO2) and fine particulate matter (PM2.5) emissions in many countries. We aim to quantify the changes in these pollutants and to assess the attributable changes in mortality in Jiangsu, China; California, U.S.; Central-southern Italy; and Germany during COVID-19 lockdowns in early 2020. Accounting for meteorological impacts and air pollution time trends, we use a machine learning-based meteorological normalization technique and the difference-in-differences approach to quantify the changes in NO2 and PM2.5 concentrations due to lockdowns. Using region-specific estimates of the association between air pollution and mortality derived from a causal modeling approach using data from 2015 to 2019, we assess the changes in mortality attributable to the air pollution changes caused by the lockdowns in early 2020. During the lockdowns, NO2 reductions avoided 1.41 (95% empirical confidence interval [eCI]: 0.94, 1.88), 0.44 (95% eCI: 0.17, 0.71), and 4.66 (95% eCI: 2.03, 7.44) deaths per 100,000 people in Jiangsu, China; California, U.S.; and Central-southern Italy, respectively. Mortality benefits attributable to PM2.5 reductions were also significant, albeit of a smaller magnitude. For Germany, the mortality benefits attributable to NO2 changes were not significant (0.11; 95% eCI: -0.03, 0.25), and an increase in PM2.5 concentrations was associated with an increase in mortality of 0.35 (95% eCI: 0.22, 0.48) deaths per 100,000 people during the lockdown. COVID-19 lockdowns overall improved air quality and brought attributable health benefits, especially associated with NO2 improvements, with notable heterogeneity across regions. This study underscores the importance of accounting for local characteristics when policymakers adapt successful emission control strategies from other regions.

Fully automatic online geometric calibration for non-circular cone-beam CT orbits using fiducials with unknown placement.

BACKGROUND: Cone-beam CT (CBCT) with non-circular scanning orbits can improve image quality for 3D intraoperative image guidance. However, geometric calibration of such scans can be challenging. Existing methods typically require a prior image, specialized phantoms, presumed repeatable orbits, or long computation time. PURPOSE: We propose a novel fully automatic online geometric calibration algorithm that does not require prior knowledge of fiducial configuration. The algorithm is fast, accurate, and can accommodate arbitrary scanning orbits and fiducial configurations. METHODS: The algorithm uses an automatic initialization process to eliminate human intervention in fiducial localization and an iterative refinement process to ensure robustness and accuracy. We provide a detailed explanation and implementation of the proposed algorithm. Physical experiments on a lab test bench and a clinical robotic C-arm scanner were conducted to evaluate spatial resolution performance and robustness under realistic constraints. RESULTS: Qualitative and quantitative results from the physical experiments demonstrate high accuracy, efficiency, and robustness of the proposed method. The spatial resolution performance matched that of our existing benchmark method, which used a 3D-2D registration-based geometric calibration algorithm. CONCLUSIONS: We have demonstrated an automatic online geometric calibration method that delivers high spatial resolution and robustness performance. This methodology enables arbitrary scan trajectories and should facilitate translation of such acquisition methods in a clinical setting.

Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse.

Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36-40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36-40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.

MAT2A inhibits the ferroptosis in osteosarcoma progression regulated by miR-26b-5p.

Osteosarcoma (OS) is the most frequent primary malignant bone tumor. Ferroptosis, a form of regulated cell death, is a key tumor suppression mechanism. Although methionine adenosyltransferase II alpha (MAT2A) has been reported to inhibit several tumor cells, it is unclear whether inhibition of MAT2A in OS cells can reduce ferroptosis. CCK-8, flow cytometry, and Transwell assays were performed to evaluate cell viability, cell apoptosis/cycle, and cell migration, respectively. The levels of ferrous iron and glutathione (GSH) levels in cells were measured to evaluate the degree of cell ferroptosis. Western blot analysis was performed to detect protein levels of MAT2A, p-STAT3 (Ser727)/STAT3, and solute carrier family 7 member 11 (SLC7A11) in OS cells. MAT2A was significantly upregulated in OS specimens and high MAT2A expression was associated with a poorer prognosis in OS patients. shRNA targeting MAT2A significantly increased OS cell apoptosis, triggered cell cycle arrest in the G2 phase, and attenuated migration ability in vitro. MAT2A depletion dramatically inhibited tumor progression of OS in vivo. Overexpression of MAT2A rescued the tumor inhibition caused by miR-26b-5p. MAT2A knockdown promoted OS cell ferroptosis. miR-26b-5p/MAT2A regulates tumor malignant progression and OS cell ferroptosis by controlling p-STAT3 and SLC7A11 expressions. Taken together, our study displayed that miR-26b-5p/MAT2A triggers ferroptosis in OS cells by increasing intracellular ferrous iron levels and inhibiting the STAT3/SLC7A11 axis. Our results reveal a MAT2A-mediated ferroptosis defense mechanism used by OS cells and propose a potential ferroptosis-inducing strategy for the treatment of OS patients.

Racial/ethnic disparities in PM2.5-attributable cardiovascular mortality burden in the United States.

Average ambient fine particulate matter (PM2.5) concentrations have decreased in the US in recent years, but the health benefits of this improvement among different racial/ethnic groups are unknown. We estimate the associations between long-term exposure to ambient PM2.5 and cause-specific cardiovascular disease (CVD) mortality rate and assess the PM2.5-attributable CVD deaths by race/ethnicity across 3,103 US counties during 2001-2016 (n = 595,776 county-months). A 1 µg m-3 increase in PM2.5 concentration was associated with increases of 7.16 (95% confidence interval (CI): 3.81, 10.51) CVD deaths per 1,000,000 Black people per month, significantly higher than the estimates for non-Hispanic white people (1.76 (95% CI: 1.37, 2.15); difference in coefficients: 5.40 (95% CI: 2.03, 8.77), P = 0.001). No significant difference in this association was observed between Hispanic (2.66 (95% CI: -0.03, 5.35)) and non-Hispanic white people (difference in coefficients: 0.90 (95% CI: -1.81, 3.61), P = 0.523). From 2001 to 2016, the absolute disparity in PM2.5-attributable CVD mortality burden was reduced by 44.04% between non-Hispanic Black and white people and by 2.61% between Hispanic and non-Hispanic white people. However, in 2016, the burden remained 3.47 times higher for non-Hispanic Black people and 0.45 times higher for Hispanic people than for non-Hispanic white people. We call for policies that aim to reduce both exposure and vulnerability to PM2.5 for racial/ethnic minorities.

Peptide-Appended Nanosonosensitizers Targeting Tumor Glycolysis for Synergistic Sonodynamic-Immunometabolic Therapy of Spinal-Metastasized Tumors.

Despite recent advancements in cancer immunotherapy, challenges have yet to be surmounted to achieve two major goals of magnifying antitumor immunity and remodeling the immunosuppressive tumor microenvironment. Here, a nanosystem (ODM-R) that integrates oxygen-deficient molybdenum oxide (ODM) nanosonosensitizers and R7 peptides with tumor metabolism regulation effects is designed and fabricated for synergistic sonodynamic-immunometabolic therapy of spinal-metastasized tumors. The ODM generates reactive oxygen species upon ultrasound irradiation to implement sonodynamic therapy (SDT), inducing cancer cell apoptosis and immunogenic cell death. The R7 attached on ODM markedly inhibits the uptake of glucose and excretion of lactic acid in cancer cells by perturbing the glycolysis process. The combination of SDT and tumor glycolysis obstruction by ODM-R guarantees satisfactory efficacy in synergizing with PD-L1 antibody to eradicate spinal-metastasized tumors, achieving concurrent sonodynamic-triggered immune activation and immunosuppressive tumor microenvironment remodeling. This work provides a proof-of-concept of nanosonosensitizers for boosting cancer immunotherapy by SDT and tumor metabolic regulation.

Technical note: Extended longitudinal and lateral 3D imaging with a continuous dual-isocenter CBCT scan.

BACKGROUND: The clinical benefits of intraoperative cone beam CT (CBCT) during orthopedic procedures include (1) improved accuracy for procedures involving the placement of hardware and (2) providing immediate surgical verification. PURPOSE: Orthopedic interventions often involve long and wide anatomical sites (e.g., lower extremities). Therefore, in order to ensure that the clinical benefits are available to all orthopedic procedures, we investigate the feasibility of a novel imaging trajectory to simultaneously expand the CBCT field-of-view longitudinally and laterally. METHODS: A continuous dual-isocenter imaging trajectory was implemented on a clinical robotic CBCT system using additional real-time control hardware. The trajectory consisted of 200° circular arcs separated by alternating lateral and longitudinal table translations. Due to hardware constraints, the direction of rotation (clockwise/anticlockwise) and lateral table translation (left/right) was reversed every 400°. X-ray projections were continuously acquired at 15 frames/s throughout all movements. A whole-body phantom was used to verify the trajectory. As comparator, a series of conventional large volume acquisitions were stitched together. Image quality was quantified using Root Mean Square Deviation (RMSD), Mean Absolute Percentage Deviation (MAPD), Structural Similarity Index Metric (SSIM) and Contrast-to-Noise Ratio (CNR). RESULTS: The imaging volume produced by the continuous dual-isocenter trajectory had dimensions of L = 95 cm × W = 45 cm × H = 45 cm. This enabled the hips to the feet of the whole-body phantom to be captured in approximately half the imaging dose and acquisition time of the 11 stitched conventional acquisitions required to match the longitudinal and lateral imaging dimensions. Compared to the stitched conventional images, the continuous dual-isocenter acquisition had RMSD of 4.84, MAPD of 6.58% and SSIM of 0.99. The CNR of the continuous dual-isocenter and stitched conventional acquisitions were 1.998 and 1.999, respectively. CONCLUSION: Extended longitudinal and lateral intraoperative volumetric imaging is feasible on clinical robotic CBCT systems.

Revealing pelvic structures in the presence of metal hip prothesis via non-circular CBCT orbits.

As the expansion of Cone Beam CT (CBCT) to new interventional procedures continues, the burdensome challenge of metal artifacts remains. Photon starvation and beam hardening from metallic implants and surgical tools in the field of view can result in the anatomy of interest being partially or fully obscured by imaging artifacts. Leveraging the flexibility of modern robotic CBCT imaging systems, implementing non-circular orbits designed for reducing metal artifacts by ensuring data-completeness during acquisition has become a reality. Here, we investigate using non-circular orbits to reduce metal artifacts arising from metallic hip prostheses when imaging pelvic anatomy. As a first proof-of-concept, we implement a sinusoidal and a double-circle-arc orbit on a CBCT test bench, imaging a physical pelvis phantom, with two metal hip prostheses, housing a 3D-printed iodine-filled radial line-pair target. A standard circular orbit implemented with the CBCT test bench acted as comparator. Imaging data collection and processing, geometric calibration and image reconstruction was completed using in-house developed software programs. Imaging with the standard circular orbit, image artifacts were observed in the pelvic bones and only 33 out of the possible 45 line-pairs of the radial line-pair target were partially resolvable in the reconstructed images. Comparatively, imaging with both the sinusoid and double-circle-arc orbits reduced artifacts in the surrounding anatomy and enabled all 45 line-pairs to be visibly resolved in the reconstructed images. These results indicate the potential of non-circular orbits to assist in revealing previously obstructed structures in the pelvic region in the presence of metal hip prosthesis.

Biomimetic Structural Protein Based Magnetic Responsive Scaffold for Enhancing Bone Regeneration by Physical Stimulation on Intracellular Calcium Homeostasis.

The bone matrix has distinct architecture and biochemistry which present a barrier to synthesizing bone-mimetic regenerative scaffolds. To mimic the natural structures and components of bone, biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) are prepared using a facile synthetic methodology. The ECM/RSF/MNP scaffold is a hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers. The scaffold demonstrates saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the ß-sheet crystalline domain of RSF and the chelated MNP could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by ≈20%. The results indicate that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promotes cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro, and new bone formation in a critical-size femur defect rat model. RNA sequencing reveals that the molecular mechanisms underlying this osteogenic effect involve calsequestrin-2-mediated Ca2+ release from the endoplasmic reticulum to activate Ca2+ /calmodulin/calmodulin-dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition, and external physical stimulation on intracellular Ca2+ homeostasis.