An Integrated Approach using YOLOv8 and ResNet, SeResNet & Vision Transformer (ViT) Algorithms based on ROI Fracture Prediction in X-ray Images of the Elbow.

INTRODUCTION: In this study, we harnessed three cutting-edge algorithms' capabilities to refine the elbow fracture prediction process through X-ray image analysis. Employing the YOLOv8 (You only look once) algorithm, we first identified Regions of Interest (ROI) within the X-ray images, significantly augmenting fracture prediction accuracy. METHODS: Subsequently, we integrated and compared the ResNet, the SeResNet (Squeeze-and-Excitation Residual Network) ViT (Vision Transformer) algorithms to refine our predictive capabilities. Furthermore, to ensure optimal precision, we implemented a series of meticulous refinements. This included recalibrating ROI regions to enable finer-grained identification of diagnostically significant areas within the X-ray images. Additionally, advanced image enhancement techniques were applied to optimize the X-ray images' visual quality and structural clarity. RESULTS: These methodological enhancements synergistically contributed to a substantial improvement in the overall accuracy of our fracture predictions. The dataset utilized for training, testing & validation, and comprehensive evaluation exclusively comprised elbow X-ray images, where predicting the fracture with three algorithms: Resnet50; accuracy 0.97, precision 1, recall 0.95, SeResnet50; accuracy 0.97, precision 1, recall 0.95 & ViTB- 16 with high accuracy of 0.99, precision same as the other two algorithms, with a recall of 0.95. CONCLUSION: This approach has the potential to increase the precision of diagnoses, lessen the burden of radiologists, easily integrate into current medical imaging systems, and assist clinical decision-making, all of which could lead to better patient care and health outcomes overall.

Investigation of electrocatalysis for tiered-tower micro-electro-mechanical-system-based biosensors: application in the early detection of the thrombosis factor trimethylamine N-oxide.

Trimethylamine N-oxide (TMAO) has been recognized as a biomarker for the early detection of thrombosis. However, testing for TMAO typically requires expensive laboratory equipment and skilled technicians, making it unsuitable for home care pre-screening. To enable its widespread use in home applications, it is crucial to develop a scalable and sensitive device capable of catalyzing TMAO metabolism with a specific enzyme that is tailored for point-of-care use. This study presents an investigation of a MEMS-based two-tiered-tower biosensor array with a detection limit of 0.1 µM for TMAO, aiming to diagnose chronic metabolic diseases using urine or serum samples. Based on the augmented Cole-Cole model, the proposed parameters R_catalyzed, C_catalyzed, and Rp_catalyzed can predict the catalytic impedance of enzymatic activities such as the redox effects of analytes and characterize the small-signal current caused by catalysis. The proposed MEMS biosensor, integrated with a readout circuitry, demonstrates a high sensitivity of 41 ADC counts per µM TMAO (or 4.5 mV µM-1 TMAO), a response time of 1 second, a repetition rate of 98.9%, and a drift over time of 0.5 mV. The sensor effectively distinguishes TMAO based on minute capacitance changes induced by the TorA enzyme, resulting in a discernible distinction of 10.6%. These measurements were successfully compared to conventional cyclic voltammetry (CV) results, showing a variance of only 0.024%. The proposed biosensor is well-suited for pre-screening thrombosis factors for the early detection and prevention of thrombosis in point-of-care applications. The device is cost-effective, lightweight, and demonstrates excellent performance, with a conversion rate of 88% of TMAO and a selectivity rate of 97% for the by-product TMA, allowing for the prediction of cardiovascular risks.

Efficacy and safety of videolaryngoscopes for transesophageal echocardiography probe insertion: A trial sequential meta-analysis.

OBJECTIVE: This meta-analysis aimed to compare videolaryngoscope (VL)-assisted transesophageal echocardiography (TEE) probe insertion with conventional methods in terms of efficacy and safety. METHODS: Several major databases such as Medline and Embase were systematically searched to identified relevant studies from inception to June 2024. The primary outcome was complication rate, defined as the proportion of patients experiencing complications related to TEE probe insertion. Injuries at specific sites (e.g., posterior hypopharyngeal wall) from both groups were also analyzed. The secondary outcomes included the first-attempt success rate and total insertion time of VL and conventional methods. RESULTS: Seven trials involving 716 participants were identified. The use of VL was found to significantly reduce the complication rate (risk ratio[RR]:0.28, 95% confidence interval[CI]:0.17-0.46, P < 0.00001) and increased the first-attempt success rate [FASR] (RR:1.33, 95%CI: 1.10-1.60, P = 0.003) compared with conventional methods. These findings were confirmed by trial sequential analysis. No significant difference was found in the TEE insertion time among the two techniques (mean difference: -2.94s, 95%CI: -10.28-4.4, P = 0.43). VL significantly reduced the risk of trauma to the hypopharyngeal wall but showed no significant benefits in other areas (e.g., pyriform sinus). The certainty of evidence was moderate for the complication rate, very low for the FAS rate, and low for the TEE insertion time. CONCLUSION: The use of VL for TEE probe insertion is associated with a significantly lower complication rate and higher FAS rate than conventional methods. These findings suggest that VL enhances patient safety and improves the efficiency of TEE probe insertion.

Association between residential noise exposure and burnout among healthcare workers in Taiwan: a cross-sectional study.

Few studies have explored the association between residential noise exposure and burnout. In this study, we investigated the association between residential noise exposure and burnout prevalence among 5416 health-care workers in Taiwan from 2012 to 2017. Burnout was evaluated using the Mandarin version of the Copenhagen Burnout Inventory by considering both continuous and binary measures. We applied ordinary Kriging models to calculate the annual average residential noise exposure at an individual level. Multivariable linear regression models and logistic regression models were employed. Restricted cubic splines were used to explore dose-response relationships. The median age of the health-care workers was 31.5 years. In the multivariable linear regression models, exposure to residential noise (per 1 dBA) was associated with increases in personal burnout and work-related burnout scores by 1.59 ± 0.25 and 1.38 ± 0.20, respectively. In the multivariable logistic regression models, the adjusted odds ratios were 1.24 (95% confidence interval [CI]: 1.16, 1.32) for personal burnout and 1.19 (95% CI: 1.13, 1.26) for work-related burnout per 1-dBA increase in residential noise exposure. Linear dose-response associations of burnout with residential noise level were detected. Our findings suggest that exposure to residential noise may increase the risk of burnout among health-care workers.

The synergistic mechanisms of propofol with cisplatin or doxorubicin in human ovarian cancer cells.

BACKGROUND: Most ovarian cancer cases are diagnosed at an advanced stage, leading to poor outcomes and a relatively low 5-year survival rate. While tumor resection in the early stages can be highly effective, recurrence following primary treatment remains a significant cause of mortality. Propofol is a commonly used intravenous anesthetic agent in cancer resection surgery. Previous research has shown that propofol anesthesia was associated with improved survival in patients undergoing elective surgery for epithelial ovarian cancer. However, the underlying antitumor mechanisms are not yet fully understood. METHODS: This study aimed to uncover the antitumor properties of propofol alone and combined with cisplatin or doxorubicin, in human SKOV3 and OVCAR3 ovarian cancer cells. We applied flowcytometry analysis for mitochondrial membrane potential, apoptosis, and autophagy, colony formation, migration, and western blotting analysis. RESULTS: Given that chemotherapy is a primary clinical approach for managing advanced and recurrent ovarian cancer, it is essential to address the limitations of current chemotherapy, particularly in the use of cisplatin and doxorubicin, which are often constrained by their side effects and the development of resistance. First of all, propofol acted synergistically with cisplatin and doxorubicin in SKOV3 cells. Moreover, our data further showed that propofol suppressed colony formation, disrupted mitochondrial membrane potential, and induced apoptosis and autophagy in SKOV3 and OVCAR3 cells. Finally, the effects of combined propofol with cisplatin or doxorubicin on mitochondrial membrane potential, apoptosis, autophagy, and epithelial-mesenchymal transition were different in SKOV3 and OVCAR3 cells, depending on the p53 status. CONCLUSION: In summary, repurposing propofol could provide novel insights into the existing chemotherapy strategies for ovarian cancer. It holds promise for overcoming resistance to cisplatin or doxorubicin and may potentially reduce the required chemotherapy dosages and associated side effects, thus improving treatment outcomes.

Simultaneous lung and renal squamous cell carcinoma: A diagnostic and treatment challenge.

This article discusses a case study of a 68-year-old male patient with lung squamous cell carcinoma (LUSC) who developed solitary renal metastasis. The importance of routine imaging for detecting asymptomatic renal metastasis is highlighted. The efficacy of various treatment options, including nephrectomy, stereotactic body radiation therapy, and cryoablation, is explored. The study underscores the need for a multidisciplinary team approach in managing LUSC with renal metastasis, due to the lack of clear treatment guidelines.

Porous Silicon-Supported Catalytic Materials for Energy Conversion and Storage.

Porous silicon (Si) has a tetrahedral structure similar to that of sp3- hybridized carbon atoms in a typical diamond structure, which affords it unique chemical and physical properties including an adjustable intrinsic bandgap, a high-speed carrier transfer efficiency. It has shown great potential in photocatalysis, rechargeable batteries, solar cells, detectors, and electrocatalysis. This review introduces various porous Si-supported electrocatalysts and analyzes the reasons why porous Si is used as a new carrier/active sites from the perspectives of its molecular structure, electronic properties, synthesis methods, etc. The electrochemical applications of porous Si-based electrocatalysts in energy conversion reactions such as hydrogen evolution reaction, oxygen evolution reaction, oxygen reduction reaction, and total water decomposition together with lithium-ion batteries (LIBs) and supercapacitors in energy storage are summarized. The challenges and future research directions for porous Si are also discussed. This review aims to deepen the understanding of porous Si and promote the development and applications of this new type of Si material.

Inserting colloidal quantum dots into GaN mesa-array subsurface porous structures through electrochemical etching for display color conversion application.

High-efficiency photon color conversion is an approach of great potential for implementing color display. Inspired by the observation of emission enhancement in a nanoscale cavity, a novel technique to fabricate an array of color converter by mixing colloidal quantum dots (QDs) with the electrolyte of an electrochemical etching (ECE) process is demonstrated. In this process, QDs flow with the electrolyte into the etched subsurface nanoscale porous structure (PS) and settle inside. Since the PS formation and hence QD insertion are controlled by the flow path of the applied electric current in the ECE process, this technique can be used for fabricating any graphic pattern. The nanostructure of such a QD-inserted mesa is examined to confirm QD insertion. Although only single-color mesa arrays are demonstrated in this paper, this technique can be used for fabricating a multiple-color mesa array if a QD or a light-emitting nanoparticle of higher thermal stability is available.

Investigation of the abasic sites induced by hydrogen peroxide and methyl methanesulfonate in calf thymus DNA and BEAS-2B cells.

The primary goals of this study were to investigate the formation of abasic sites (AP sites) induced by methyl methanesulfonate (MMS) and hydrogen peroxide (H2O2), and to characterize specific types of these pro-mutagenic DNA lesions in calf thymus DNA (CT-DNA), and BEAS-2B human lung normal cell line. Furthermore, these profiles were compared with those observed in leukocytes derived from healthy controls (HC), breast cancer patients (BCP) before treatment, and 5-year survivors. Results indicated that both H2O2 and MMS induced the concentration- and time-dependent formation of AP sites in CT-DNA. To characterize the specific types of AP sites induced by H2O2 or MMS, we performed AP site cleavage assay using putrescine, T7 exonuclease (T7 Exo), and exonuclease III (Exo III). Results showed that the AP sites induced by H2O2 in CT-DNA were predominantly 5'-and 3'-nicked AP sites and no intact AP sites were detected. By contrast, the majority of AP sites generated by MMS in CT-DNA are not excisable and are classified as residual and intact AP sites. Similar approaches were performed in human BEAS-2B cells and comparable observations were confirmed in the cell-based model. Further investigation indicated that the profile of the AP sites observed in Taiwanese HC is identical to that of BEAS-2B cells treated with H2O2 whereas the pattern of AP sites detected in BCP is similar to that of CT-DNA exposed to H2O2, suggesting that these AP sites were produced primarily through reactive oxygen species (ROS) generation. More than 70 % of the AP sites in leukocytes derived from BCP were 5'-nicked and residual AP sites. Furthermore, the characteristics of the AP sites detected in 5-year survivors are comparable with the ones in HC by using putrescine cleavage assay. Overall, we speculate that deficiency in the DNA repair cascade may play a role in mediating the formation of specific types of AP sites detected in BCP.

Availability of Using Honeybees and Hive Products as Bioindicators of Ambient Pesticide Exposure in Taiwan.

Honeybees and hive products could be used as bioindicators of pesticide exposure in surrounding areas, but the associations have rarely been examined. We collected samples of bees, hive products and environmental dust from 12 apiaries during the blooming season in eastern Taiwan and assessed the relationships between pesticides in apiarian samples and the environment. Samples were analyzed for 14 pesticides using gas or liquid chromatography coupled with mass spectrometry. Sick bees, dead bees, bee pollen, beeswax and environmental dust in the outer rings (>150 m) surrounding the apiaries were contaminated with high levels of pesticides (mean concentration: >270 ng/g in total). In terms of concentrations of all pesticides, insecticides, herbicides and fungicides, most apiarian sample matrices were significantly correlated with environmental dust within a range of 2.5 km (ρ > 0.6, p < 0.05), suggesting their potential as bioindicators. Of those apiarian matrices with high contamination contents, dead bees or beeswax may be a good bioindicator for all pesticides but not for herbicides, because of the insignificant correlation with environmental dust (ρ < 0.5). For all types of pesticides, we recommend sick bees and bee pollen as choices for bioindicators, because of their high contamination levels for detection and complete representativeness of the environment.

A Comparative Analysis of U-Net and Vision Transformer Architectures in Semi-Supervised Prostate Zonal Segmentation.

The precise segmentation of different regions of the prostate is crucial in the diagnosis and treatment of prostate-related diseases. However, the scarcity of labeled prostate data poses a challenge for the accurate segmentation of its different regions. We perform the segmentation of different regions of the prostate using U-Net- and Vision Transformer (ViT)-based architectures. We use five semi-supervised learning methods, including entropy minimization, cross pseudo-supervision, mean teacher, uncertainty-aware mean teacher (UAMT), and interpolation consistency training (ICT) to compare the results with the state-of-the-art prostate semi-supervised segmentation network uncertainty-aware temporal self-learning (UATS). The UAMT method improves the prostate segmentation accuracy and provides stable prostate region segmentation results. ICT plays a more stable role in the prostate region segmentation results, which provides strong support for the medical image segmentation task, and demonstrates the robustness of U-Net for medical image segmentation. UATS is still more applicable to the U-Net backbone and has a very significant effect on a positive prediction rate. However, the performance of ViT in combination with semi-supervision still requires further optimization. This comparative analysis applies various semi-supervised learning methods to prostate zonal segmentation. It guides future prostate segmentation developments and offers insights into utilizing limited labeled data in medical imaging.

Comparing subjective quality of recovery between remimazolam- and propofol-based total intravenous anesthesia for surgical procedures: a meta-analysis.

BACKGROUND: Remimazolam is a novel ultra-short-acting benzodiazepine that has been recently introduced as an alternative to propofol for general anesthesia. While both agents have been compared in terms of safety and efficacy, their relative effects on postoperative quality of recovery (QoR) remain unclear. Therefore, this meta-analysis aimed to compare the effects of remimazolam and propofol on subjective QoR in surgical patients who underwent general anesthesia. METHODS: Medline, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched from inception to May 28, 2024 to identify randomized controlled trials comparing remimazolam and propofol in terms of postoperative QoR. The Cochrane risk-of-bias tool (RoB 2) was used to assess study quality. QoR score on postoperative day (POD) 1 (primary outcome), QoR scores on PODs 2-3, QoR dimensions, time to loss of consciousness, other recovery characteristics, and rescue analgesia requirement were evaluated using random-effects meta-analyses. RESULTS: This meta-analysis included 13 studies published between 2022 and 2024 involving 1,418 patients. QoR was evaluated using either the QoR-15 (10 studies) or QoR-40 (3 studies) questionnaire. The pooled results indicated no significant difference in the QoR scores on POD 1 (standardized mean difference: 0.02, 95% confidence interval [CI]: - 0.20, 0.23, P = 0.88, I2 = 73%) and PODs 2-3 between remimazolam and propofol. Furthermore, no significant differences were observed in QoR dimensions, length of postanesthesia care unit (PACU) stay, and time to extubation as well as in the risks of agitation and postoperative nausea and vomiting. Patients administered remimazolam exhibited slower anesthetic induction (mean difference (MD): 32.27 s) but faster recovery of consciousness (MD: - 1.60 min) than those administered propofol. Moreover, remimazolam was associated with a lower risk of rescue analgesia requirement in the PACU (risk ratio: 0.62, 95% CI: 0.43, 0.89, P = 0.009, I2 = 0%) but not in the ward. CONCLUSION: Remimazolam is a potential alternative to propofol for general anesthesia as it offers similar QoR to the latter and has advantages in terms of consciousness recovery and immediate postoperative analgesia requirement.

A novel protein SPECC1-415aa encoded by N6-methyladenosine modified circSPECC1 regulates the sensitivity of glioblastoma to TMZ.

BACKGROUND: Circular RNAs (circRNAs) can influence a variety of biological functions and act as a significant role in the progression and recurrence of glioblastoma (GBM). However, few coding circRNAs have been discovered in cancer, and their role in GBM is still unknown. The aim of this study was to identify coding circRNAs and explore their potential roles in the progression and recurrence of GBM. METHODS: CircSPECC1 was screened via circRNAs microarray of primary and recurrent GBM samples. To ascertain the characteristics and coding ability of circSPECC1, we conducted a number of experiments. Afterward, through in vivo and in vitro experiments, we investigated the biological functions of circSPECC1 and its encoded novel protein (SPECC1-415aa) in GBM, as well as their effects on TMZ sensitivity. RESULTS: By analyzing primary and recurrent GBM samples via circRNAs microarray, circSPECC1 was found to be a downregulated circRNA with coding potential in recurrent GBM compared with primary GBM. CircSPECC1 suppressed the proliferation, migration, invasion, and colony formation abilities of GBM cells by encoding a new protein known as SPECC1-415aa. CircSPECC1 restored TMZ sensitivity in TMZ-resistant GBM cells by encoding the new protein SPECC1-415aa. The m6A reader protein IGF2BP1 can bind to circSPECC1 to promote its expression and stability. Mechanistically, SPECC1-415aa can bind to ANXA2 and competitively inhibit the binding of ANXA2 to EGFR, thus resulting in the inhibition of the phosphorylation of EGFR (Tyr845) and its downstream pathway protein AKT (Ser473). In vivo experiments showed that the overexpression of circSPECC1 could combine with TMZ to treat TMZ-resistant GBM, thereby restoring the sensitivity of TMZ-resistant GBM to TMZ. CONCLUSIONS: CircSPECC1 was downregulated in recurrent GBM compared with primary GBM. The m6A reader protein IGF2BP1 could promote the expression and stability of circSPECC1. The sequence of SPECC1-415aa, which is encoded by circSPECC1, can inhibit the binding of ANXA2 to EGFR by competitively binding to ANXA2 and inhibiting the phosphorylation of EGFR and AKT, thereby restoring the sensitivity of TMZ-resistant GBM cells to TMZ.

Polystyrene microplastics alleviate the developmental toxicity of silver nanoparticles in embryo-larval zebrafish (Danio rerio) at the transcriptomic level.

Since silver nanoparticles (AgNPs) and polystyrene microplastics (PS-MP) share common environmental niches, their interactions can modulate their hazard impacts. Herein, we assessed the developmental toxicity of 1 mg/L PS-MP, 0.5 mg/L AgNPs and the mixtures of AgNPs and PS-MP on embryo-larval zebrafish. We found that AgNPs co-exposure with PS-MP remarkably decreased mortality rates, malformation rates, heart rates and yolk sac area, while it increased hatching rates and eye size compared to the AgNPs group. These phenomena revealed that the cell cycle, oxidative stress, apoptosis, lipid metabolism, ferroptosis and p53 signalling pathway were obviously affected by single AgNPs exposure at 96 hpf (hours post fertilization). Interestingly, all these effects were effectively ameliorated by co-exposure with PS-MP. The combination of transcriptomic and metabolomic analyses showed that the imbalance of DEGs (differentially expressed genes) and DEMs (differentially expressed metabolites) (PI, phosphatidylinositol and TAG-FA, triacylglycerol-fatty acid) disturbed both the cell cycle and lipid metabolism following single AgNPs exposure and co-exposure with PS-MP. These findings suggest that PS-MP attenuates the developmental toxicity of AgNPs on embryo-larval zebrafish. Overall, this study provides important insight into understanding the transcriptional responses and mechanisms of AgNPs alone or in combination with PS-MPs on embryo-larval zebrafish, providing a reference for ecological risk assessment of combined exposure to PS-MP and metal nanoparticles.

Interleukin-12p40 deficiency attenuates myocardial ferroptosis in doxorubicin-induced chronic cardiomyopathy by inhibiting Th17 differentiation and interleukin-17A production.

AIMS: Interleukin (IL)-12p40 is a common subunit of the bioactive cytokines IL-12 and IL-23, and it also has its own intrinsic functional activity. However, its role in doxorubicin-induced chronic cardiomyopathy (DICCM) as well as the underlying mechanisms are still unknown. METHODS AND RESULTS: In this study, we used IL-12p40-knockout mice, IL-23p19-knockout mice, Rag1-knockout mice, a ferroptosis inhibitor, recombinant IL-12 (rIL-12), rIL-23, rIL-12p40, rIL-12p80, and anti-IL17A to investigate the effects of IL-12p40 on DICCM and elucidate the underlying mechanisms. We found that myocardial ferroptosis were increased in DICCM and that the inhibition of ferroptosis protected against DICCM. The expression of IL-12p40 was upregulated, and IL-12p40 was predominantly expressed by CD4+ T cells in the hearts of mice with DICCM. IL-12p40 knockout attenuated cardiac dysfunction, fibrosis and ferroptosis in DICCM, and similar results were observed in the context of CD4+ T cell IL-12p40 deficiency in Rag1-/- mice. Treatment with rIL-23, but not rIL-12, rIL-12p40 monomer or rIL-12p80, abolished the protective effects of IL-12p40 knockout. Moreover, rIL-23 treatment and IL-23p19 knockout exacerbated and ameliorated DICCM, respectively. IL-12p40 knockout might protect against DICCM by inhibiting Th17 differentiation and IL-17A production but not Th1, Th2 and Treg differentiation. Neutralizing IL-17A with an antibody also attenuated cardiac dysfunction, fibrosis and ferroptosis. The IL-12p40/Th17/IL-17A axis might promote cardiomyocyte ferroptosis by activating TNF receptor-associated factor 6 (TRAF6)/mitogen-activated protein kinase (MAPK)/P53 signaling in DICCM. CONCLUSIONS: Interleukin-12p40 deficiency protects against DICCM by inhibiting Th17 differentiation and the production of IL-17A, which plays critical roles in cardiomyocyte ferroptosis in DICCM via activating TRAF6/MAPK/P53 signaling. Our study may provide novel insights for the identification of therapeutic targets for treating DICCM in the clinic.

Designing 2D carbon dot nanoreactors for alcohol oxidation coupled with hydrogen evolution.

The coupled green energy and chemical production by photocatalysis represents a promising sustainable pathway, which poses great challenges for the multifunction integration of catalytic systems. Here we show a promising green photocatalyst design using Cu-ZnIn2S4 nanosheets and carbon dots as building units, which enables the integration of reaction, mass transfer, and separation functions in the nano-space, mimicking a nanoreactor. This function integration results in great activity promotion for benzyl alcohol oxidation coupled H2 production, with H2/benzaldehyde production rates of 45.95/46.47 mmol g-1 h-1, 36.87 and 36.73 times to pure ZnIn2S4, respectively, owning to the enhanced charge accumulation and mass transfer according to in-situ spectroscopies and computational simulations of the built-in electrical field. Near-unity selectivity of benzaldehyde is achieved via the effective separation enabled by the Cu(II)-mediated conformation flipping of the intermediates and subsequent π-π conjugation. This work demonstrates an inspiring proof-of-concept nanoreactor design of photocatalysts for coupled sustainable systems.

Lag screw versus locking plate fixation for traumatic displaced medial malleolar fractures: a systematic review and meta-analysis.

BACKGROUND: Lag screw fixation (LSF) or locking plate fixation (LPF) are both recommended for the treatment of medial malleolar fractures (MMFs). However, no standard has been established for attaining optimal surgical treatment or functional recovery. We hypothesized that LPF for MMFs would result in superior outcomes compared to LSF. To test this hypothesis, we conducted a systematic review and meta-analysis of the clinical outcomes of LSF and LPF in the treatment of MMF. PATIENTS AND METHODS: We searched for studies published prior to November 2023 across the PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases. Standardization of individual effect sizes was conducted; subsequently, pooled effect sizes were derived by employing random-effects models. RESULTS: Five retrospective studies involving 394 patients were reviewed. American Orthopedic Foot and Ankle Society (AOFAS) scores were significantly higher among patients who received LPF (mean difference [MD]: 2.21; 95% confidence interval [CI]: 0.37-4.04; p = 0.02) than among those who received LSF. Pain scores were significantly lower among patients who received LPF (MD: -0.35; 95% CI: -0.64 to -0.05; p = 0.02) than among those who received LSF. No significant differences in delayed union was observed between the groups (Relative risk [RR]: 1.43; 95% CI, 0.37-4.04; p = 0.42). Fixation failure was slightly higher in patients who received LSF than in those who received LPF (RR: 3.11; 95% CI, 0.88-11.01; p = 0.08). DISCUSSION: Compared with LSF, LPF yields superior functional outcomes, superior patient comfort, and comparative complication rates. LPF is also better able to prevent rotation and apply compressive forces across fracture sites, which can facilitate the management of different types of MMF. Additional randomized controlled trials with larger sample sizes are warranted. LEVEL OF EVIDENCE: III.

Manufacturing CD20/CD19-targeted iCasp9 regulatable CAR-TSCM cells using a Quantum pBac-based CAR-T engineering system.

CD19-targeted chimeric antigen receptor (CAR) T cell therapies have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CD19-CAR-T-treated patients experience progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant numbers of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac™ (qPB), we developed a virus-free cell-engineering system for development and production of multiplex CAR-T therapies. Here, we demonstrate in vitro and in vivo that consistent, robust and functional CD20/CD19 dual-targeted CAR-T stem cell memory (CAR-TSCM) cells can be efficiently produced for clinical application using qPB™. In particular, we showed that qPB™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. Therefore, the simplicity of manufacturing multiplex CAR-T cells using the qPB™ system has the potential to improve efficacy and broaden the accessibility of CAR-T therapies.

A novel protein encoded by circCOPA inhibits the malignant phenotype of glioblastoma cells and increases their sensitivity to temozolomide by disrupting the NONO-SFPQ complex.

Glioblastoma (GBM) represents a primary malignant brain tumor. Temozolomide resistance is a major hurdle in GBM treatment. Proteins encoded by circular RNAs (circRNAs) can modulate the sensitivity of multiple tumor chemotherapies. However, the impact of circRNA-encoded proteins on GBM sensitivity to temozolomide remains unknown. Herein, we discover a circRNA (circCOPA) through the circRNA microarray profile in GBM samples, which can encode a novel 99 amino acid protein (COPA-99aa) through its internal ribosome entry site. Functionally, circCOPA overexpression in GBM cells inhibits cell proliferation, migration, and invasion in vitro and growth in vivo. Rather than itself, circCOPA mainly functions as a suppressive effector by encoding COPA-99aa. Moreover, we reveal that circCOPA is downregulated in GBM tissues and high expression of circCOPA is related to a better prognosis in GBM patients. Mechanistically, a heteromer of SFPQ and NONO is required for double-strand DNA break repair. COPA-99aa disrupts the dimerization of NONO and SFPQ by separately binding with the NONO and SFPQ proteins, thus resulting in the inhibition of proliferation or invasion and the increase of temozolomide-induced DNA damage in GBM cells. Collectively, our data suggest that circCOPA mainly contributes to inhibiting the GBM malignant phenotype through its encoded COPA-99aa and that COPA-99aa increases temozolomide-induced DNA damage by interfering with the dimerization of NONO and SFPQ. Restoring circCOPA or COPA-99aa may increase the sensitivity of patients to temozolomide.