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Abstract This study investigated the effect of various storage media on the physicochemical properties of plasma-treated 3-mol% yttria-stabilized tetragonal zirconia: air, vacuum, deionized water (DIW), and plasma-activated water (PAW). Each group was divided into five subgroups based on storage periods: immediately after NTP irradiation (T0), and after 1 week (T1), 2 weeks (T2), 3 weeks (T3), and 4 weeks (T4). The control group (C) received no treatment. The storage groups were monitored weekly using various analytical techniques, including contact angle measurements, scanning electron microscopy (SEM), focused ion beam (FIB)-SEM, confocal laser scanning microscopy (CLSM), x-ray photoelectron spectroscopy (XPS), and x-ray diffraction (XRD). Our results demonstrate that plasma-treated zirconia surfaces stored in DIW retained or even increased their hydrophilicity due to the formation of hydrogen bonds and preservation of nitrogen functionalities. In contrast, surfaces stored in air exhibited significant hydrophobic recovery. FIB-SEM analysis showed no adverse internal structural changes regardless of storage medium. The roughness of the zirconia surface slightly increased after plasma treatment and was generally retained across all storage groups for 4 weeks, except for the air storage group. This study concludes that storage in DIW effectively preserves the enhanced surface properties of plasma-activated zirconia for up to 4 weeks.

Abstract Non-thermal plasma (NTP) is an emerging technology with extensive applications in biomedicine, including treatment of abnormal pigmentation. However, very few studies have investigated how plasma induces anti-melanogenesis. Here, liquid plasma was prepared by treating an NTP jet with helium and oxygen (as carrier gases) for 15 min in serum-free culture media. In the zebrafish model, pigmentation ratio was observed with or without liquid plasma. The anti-melanogenic effect of liquid plasma was evaluated in human melanocytes by assessing the expression of melanogenesis-related genes using western blotting, RT-PCR, and immunohistochemistry. Liquid plasma reduced pigmentation in the zebrafish model and inhibited melanin synthesis in primary human melanocytes. Intracellular reactive oxygen species levels decreased and Nrf2 expression increased in liquid plasma–treated melanocytes. Liquid plasma affected microphthalmia-associated transcription factor (MITF) and tyrosinase mRNA and protein levels, tyrosinase activity, and melanin content. Considering the role of Wnt/β-catenin and PI3K/Akt pathways in melanogenesis, the effect of liquid plasma on this pathway was determined; liquid plasma decreased active β-catenin, LEF1/TCF4, MITF, and tyrosinase levels in a time-dependent manner and inhibited the nuclear translocation of β-catenin. This inhibition subsequently suppressed melanogenesis by downregulating MITF and tyrosinase. These results suggest that liquid plasma may be used for treating pigmentary disorders.

Abstract Background Anticancer treatments aim to selectively target cancer cells without harming normal cells. While non-thermal atmospheric pressure plasma (NTAPP) has shown anticancer potential across various studies, the mechanisms behind its selective action on cancer cells remain inadequately understood. This study explores the mechanism of NTAPP-induced selective cell death and assesses its application in cancer therapy. Methods We treated HT1080 fibrosarcoma cells with NTAPP and assessed the intracellular levels of mitochondria-derived reactive oxygen species (ROS), mitochondrial function, and cell death mechanisms. We employed N-acetylcysteine to investigate ROS’s role in NTAPP-induced cell death. Additionally, single-cell RNA sequencing was used to compare gene expression in NTAPP-treated HT1080 cells and human normal fibroblasts (NF). Western blotting and immunofluorescence staining examined the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), a key antioxidant gene transcription factor. We also evaluated autophagy activity through fluorescence staining and transmission electron microscopy. Results NTAPP treatment increased ROS levels and induced mitochondrial dysfunction, leading to apoptosis in HT1080 cells. The involvement of ROS in selective cancer cell death was confirmed by N-acetylcysteine treatment. Distinct gene expression patterns were observed between NTAPP-treated NF and HT1080 cells, with NF showing upregulated antioxidant gene expression. Notably, NRF2 expression and nuclear translocation increased in NF but not in HT1080 cells. Furthermore, autophagy activity was significantly higher in normal cells compared to cancer cells. Conclusions Our study demonstrates that NTAPP induces selective cell death in fibrosarcoma cells through the downregulation of the NRF2-induced ROS scavenger system and inhibition of autophagy. These findings suggest NTAPP’s potential as a cancer therapy that minimizes damage to normal cells while effectively targeting cancer cells.

Abstract Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.

Abstract We aimed to compare the extent of bone turnover suppression between patients with atypical femoral fractures (AFFs) and osteoporotic hip fractures (typical femur fractures, TFFs) using a one-to-one matching strategy. A single-center retrospective comparison of females aged ≥ 60 years who underwent operative treatment for AFFs and TFFs between January 2010 and March 2021 was conducted. Demographic characteristics and clinical data including fracture site, past medical history, bone mineral density (BMD), bisphosphonate (BP) medication history, and serum bone turnover marker (BTM) levels were examined. Moreover, we performed a logistic regression analysis to determine the risk factors for AFFs and a one-to-one matched-pair analysis to compare various BTMs. Overall, 336 consecutive females were included: 113 with AFFs and 213 with TFFs. The mean age, BMI, and lowest BMD T-score were 78.6 years, 22.8 kg/m2, and −3.3, respectively. Patients with AFF were younger, had lower BMD, higher BMI, higher prevalence of rheumatoid arthritis, a greater proportion with previous steroid or BP use, and a longer history of BP use than patients with TFF. The 48:48 matched-pair analysis revealed higher serum 25(OH) vitamin-D (30.5 vs 18.2 ng/mL, P

Abstract Background Antimicrobial resistance is considered one of the greatest threats to human health, according to the World Health Organization (WHO). Gram-negative bacteria, especially carbapenem-resistant Enterobacteriaceae (CRE), have become a significant concern in antimicrobial-resistant bacteria’s global emergence and spread. Among CRE pathogens, carbapenem-resistant Klebsiella pneumoniae (CRKP) has recently been reported as a highly infectious strain associated with high mortality and morbidity in adults and immunocompromised patients. Additionally, CRKP-related infections are challenging to treat, as carbapenems are the last resort of antibiotics. Therefore, developing novel drugs with different mechanisms of action from existing drugs is urgently required to defeat this lethal menace. Under such circumstances, probiotics can be therapeutic candidates for inhibiting pathogens. Thus, our research team has been focusing on probiotics for a long time to develop potential anti-CRKP drug agents. Methods After extensive efforts, we finally found a novel probiotic strain, Lactobacillus sakei PMC104, suitable for treating CRKP infection. It was isolated from kimchi. As part of our expansion into therapeutic development, we evaluated the L. sakei strain effect against CRKP pathogens in both in vitro and in vivo experiments. Moreover, we conducted media optimization at food grade and then established a scale-up process on a pilot scale. Subsequently, a lyophilizate was obtained and used in a mouse model infected with CRKP. Results Data demonstrated that the L. sakei strain has an inhibitory effect against CRKP infection both in in vitro and in vivo experiments and also increases the level of short-chain fatty acids in the feces of mice after receiving L. sakei strain treatment for 10 days. Furthermore, treatment with L. sakei powder remarkably diminished body weight loss, mortality, and illness severity in CRKP-infected mice, showing a preventive effect of our PMC 104 against CRKP infection. Discussion Our results demonstrate the potential therapeutic effect of our candidate probiotic strain against CRKP, suggesting that L. sakei PMC 104 could be considered an antimicrobial candidate for treating CRKP infections. However, extensive studies, including additional toxicity tests and clinical trials, are still essential to develop it as a new anti-CRKP therapeutic agent.

Immune checkpoint blockers (ICBs) targeting programmed cell death protein 1 (PD‐1) have been proven to be an effective first‐line therapy against programmed cell death 1 ligand 1 (PD‐L1; also known as CD274 molecule)‐expressing head and neck squamous cell carcinoma (HNSCC) in recent KEYNOTE‐048 trial. However, associated changes in the tumor microenvironment (TME) and underlying mechanisms remain elusive. Oral tumors in C57/BL6 mice were induced by administering 7,12‐dimethylbenzanthracene into the buccal mucosa. Single‐cell suspension was isolated from tumor tissue; proliferating cells were injected subcutaneously into the left flank of mice to establish Ajou oral cancer (AOC) cell lines. Subsequently, a syngeneic PD‐L1‐expressing HNSCC model was developed by injecting AOC cells into the buccal or tongue area. The model recapitulated human HNSCC molecular features and showed reliable in vivo tumorigenicity with significant PD‐L1 expression. ICB monotherapy induced global changes in the TME, including vascular normalization. Furthermore, the antitumor effect of ICB monotherapy was superior to those of other therapeutic agents, including cisplatin and inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2). The ICB‐induced antitumorigenicity and TME normalization were alleviated by blocking the type I interferon pathway. In summary, ICB monotherapy is sufficient to induce TME normalization in the syngeneic model; the type I interferon pathway is indispensable in realizing the effects of ICBs. Furthermore, these results explain the underlying mechanism of the efficacy of ICB monotherapy against PD‐L1‐expressing HNSCC in the KEYNOTE‐048 trial.

Abstract This case study investigated the impact of SCS on alterations in blood pressure during constant‐load exercise in a female patient with heart failure. Three different SCS frequencies [No SCS (~0 Hz), Low SCS (~100 Hz), and High SCS (~1000 Hz)] with and without ischaemic stimulation of the legs (cuffs) were randomly applied during constant‐load exercise. To determine cardiovascular and ventilatory responses to exercise following SCS frequencies, BP, heart rate (HR), and respiratory gas exchange were measured. This experiment was duplicated in visit 1 and visit 2 with a random application of SCS frequency order and the data were averaged. There were no significant differences among three frequencies with no leg ischaemia. However, High SCS demonstrated lower BP, HR, and respiratory gas exchange relative to No SCS and Low SCS. SCS may be effective in improving cardiovascular and ventilatory responses in HF and high‐frequency stimulation provides more clinical benefit; however, further studies are needed.

Objectives Arthroscopic treatment is indicated for external snapping hip (ESH) syndrome in patients refractory to conservative treatment, but snapping does not disappear completely in some case. No previous studies have described the clinical course of ESH syndrome in patients who presented with persistent snapping after an arthroscopic procedure. We demonstrated the clinical outcomes following an incomplete arthroscopic iliotibial band (ITB) release for ESH syndrome. Methods This retrospective observational study was performed at two teaching hospitals between October 2015 and December 2021. We reviewed the data of 33 patients (34 hips) aged ≥18 years, diagnosed with ESH syndrome, who were treated with arthroscopic ITB release. Patients who presented with persistent snapping despite sufficient arthroscopic ITB release following systematic order were defined as having an incomplete release. We collected the data for recurrent symptomatic snapping hip as the primary outcome after a minimum 2‐year follow‐up. The visual analogue scale (VAS) and modified Harris hip (mHHS) scores were measured as secondary outcome. Results “Incomplete release” was identified in three of the 34 hips (8.9%). Cases of recurrent symptomatic snapping or conversion to open surgery were not observed. The symptoms of residual snapping spontaneously disappeared in all cases following routine postoperative rehabilitation within a 3‐month follow‐up period. The VAS (4 ± 1) and mHHS (17 ± 6) scores of all the patients improved. Conclusion When refractory ESH syndrome is identified during arthroscopic surgery, appropriate ITB release and removal of the major lesion causing snapping are expected to lead to resolution of residual symptoms without conversion to open surgery.

Abstract Research on the treatment outcomes and mortality of patients with cancer and hip fractures remains limited. We aimed to assess the treatment outcomes and mortality in older patients with cancer and hip fractures. We retrospectively reviewed the data of 1264 patients aged ≥ 60 years treated for hip fractures between January 2005 and April 2022. The operation time, blood transfusion-related indicators, postoperative complications, reoperation rate, length of hospital stay, admission to the intensive care unit, mortality rate, and clinical scores were compared. We also performed survival analysis. Subsequently, 1:1 propensity-score matching was performed. In the unmatched cohort, we compared 273 patients with cancer and 991 controls. The cancer group exhibited a higher incidence of pneumonia (P = 0.025) and higher in-hospital and 1-year follow-up mortality rates (P = 0.044 and P

Exosomes have garnered attention for use in bone regeneration, but their low activity, rapid degradation, and inaccurate delivery have been obstacles to their use in clinical applications. As such, there exists a need for an exosome-integrated delivery platform. Calcium silicate (Ca-Si) is considered one of the most promising bioceramics for bone regeneration because of its remarkable ability to promote hydroxyapatite formation, osteoblast proliferation, and differentiation. However, Ca-Si has limitations, such as a high degradation rate leading to high pH values. Here, we propose a bone regeneration platform: three-dimensional-fabricated Ca-Si scaffolds immersed in polycaprolactone (PCL) coated with exosomes. This setup enhanced porosity, mechanical strength, and natural hydroxyapatite formation. Ca-Si incorporation increased the quantity of attached exosomes on the scaffold and enabled more sustainable control of their release compared to bare PCL. The exosome-coated scaffold exhibited excellent cell attachment and osteogenic differentiation, significantly increasing biocompatibility and the in situ recruitment of stem cells when transplanted into the subcutaneous tissue of mice. The bone regenerating efficacy of the exosome-attached scaffold was confirmed using a mouse calvarial bone defect animal model. These findings suggest a potential application of exosome-coated Ca-Si/PCL scaffolds as an osteogenic platform for critical bone defects.

Background Using peripheral arteries to infer central hemodynamics is common among hemodynamic monitors. Doppler ultrasound of the common carotid artery has been used in this manner with conflicting results. We investigated the relationship between changing common carotid artery Doppler measures and stroke volume (SV), hypothesizing that more consecutively-averaged cardiac cycles would improve SV-carotid Doppler correlation. Methods Twenty-seven healthy volunteers were recruited and studied in a physiology laboratory. Carotid artery Doppler pulse was measured with a wearable, wireless ultrasound during central hypovolemia and resuscitation induced by a stepped lower body negative pressure protocol. The change in maximum velocity time integral (VTI) and corrected flow time of the carotid artery (ccFT) were compared with changing SV using repeated measures correlation. Results In total, 73,431 cardiac cycles were compared across 27 subjects. There was a strong linear correlation between changing SV and carotid Doppler measures during simulated hemorrhage (repeated-measures linear correlation [Rrm]=0.91 for VTI; 0.88 for ccFT). This relationship improved with larger numbers of consecutively-averaged cardiac cycles. For ccFT, beyond four consecutively-averaged cardiac cycles the correlation coefficient remained strong (i.e., Rrm of at least 0.80). For VTI, the correlation coefficient with SV was strong for any number of averaged cardiac cycles. For both ccFT and VTI, Rrm remained stable around 25 consecutively-averaged cardiac cycles. Conclusions There was a strong linear correlation between changing SV and carotid Doppler measures during central blood volume loss. The strength of this relationship was dependent upon the number of consecutively-averaged cardiac cycles.

Abstract Background Applications of nonthermal plasma have expanded beyond the biomedical field to include antibacterial, anti-inflammatory, wound healing, and tissue regeneration. Plasma enhances epithelial cell repair; however, the potential damage to deep tissues and vascular structures remains under investigation. Result This study assessed whether liquid plasma (LP) increased nitric oxide (NO) production in human umbilical vein endothelial cells by modulating endothelial NO synthase (eNOS) phosphorylation and potential signaling pathways. First, we developed a liquid plasma product and confirmed the angiogenic effect of LP using the Matrigel plug assay. We found that the NO content increased in plasma-treated water. NO in plasma-treated water promoted cell migration and angiogenesis in scratch and tube formation assays via vascular endothelial growth factor mRNA expression. In addition to endothelial cell proliferation and migration, LP influenced extracellular matrix metabolism and matrix metalloproteinase activity. These effects were abolished by treatment with NG-L-monomethyl arginine, a specific inhibitor of NO synthase. Furthermore, we investigated the signaling pathways mediating the phosphorylation and activation of eNOS in LP-treated cells and the role of LKB1-adenosine monophosphate-activated protein kinase in signaling. Downregulation of adenosine monophosphate-activated protein kinase by siRNA partially inhibited LP-induced eNOS phosphorylation, angiogenesis, and migration. Conclusion The present study suggests that LP treatment may be a novel strategy for promoting angiogenesis in vascular damage. Video Abstract Graphical Abstract

Abstract This study aimed to assess the impact of varying monopolar diathermy power settings on postoperative pain, hemorrhage, and wound healing following tonsillectomy. A single-center, prospective, randomized, double-blinded, controlled clinical study was conducted. During bilateral tonsillectomy procedures, one tonsil received low-power settings (15 W, cutting/blend) while the other tonsil received high-power settings (35 W, cutting/blend). Postoperative pain scores (0–10) and wound healing scores (0–3) were evaluated immediately after surgery and at 1, 2, and 4 weeks postoperatively using the visual analog scale. Additionally, histological analysis was performed on electrically resected tonsil tissues to assess tissue damage in the tonsil bed. The allocation of high and low power settings to each side was randomized. Results showed that 1 week after the surgery, the high-power group experienced significantly higher pain scores (mean ± standard deviation: 4.84 ± 2.21) compared to the low-power group (3.56 ± 2.24, p = 0.049). Moreover, the high-power side exhibited slower wound healing during the initial 1–2 weeks postoperatively, as indicated by lower wound scores at 2 weeks (high-power: 1.96 ± 0.64; low-power: 2.43 ± 0.59, p = 0.008). Furthermore, histological analysis revealed significantly deeper tissue degradation on the high-power side compared to the low-power side (p

OBJECTIVES The purpose of this study was to investigate the weight loss and isotonic core exercise on oswestry disability index (ODI), trunk extensor and flexor muscle strength in obese middle-aged women with chronic low back pain. METHODS Eighteen obese middle-aged woman with chronic low back pain were randomly assigned into weight loss + core exercise group (WL+CE, n=6), core exercise group (CE, n=6), and control group (CON, n=6). The weight loss goal was set at approximately 0.5-1 kg per week, and core exercises were conducted for 60 minutes, three times a week, for 8 weeks. Body composition (weight, % body fat, muscle mass, WHR), ODI, trunk extensor and flexor muscle strength were measured before, 4 weeks, and 8 weeks after core exercise. RESULTS WHR and ODI significantly decreased at 4 and 8 weeks of exercise in both the WL+CE and CE groups compared to before exercise (p

Abstract This study focused on a novel strategy that combines deep learning and radiomics to predict epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC) using computed tomography (CT). A total of 1280 patients with NSCLC who underwent contrast-enhanced CT scans and EGFR mutation testing before treatment were selected for the final study. Regions of interest were segmented from the CT images to extract radiomics features and obtain tumor images. These tumor images were input into a convolutional neural network model to extract 512 image features, which were combined with radiographic features and clinical data to predict the EGFR mutation. The generalization performance of the model was evaluated using external institutional data. The internal and external datasets contained 324 and 130 EGFR mutants, respectively. Sex, height, weight, smoking history, and clinical stage were significantly different between the EGFR-mutant patient groups. The EGFR mutations were predicted by combining the radiomics and clinical features, and an external validation dataset yielded an area under the curve (AUC) value of 0.7038. The model utilized 1280 tumor images, radiomics features, and clinical characteristics as input data and exhibited an AUC of approximately 0.81 and 0.78 during the primary cohort and external validation, respectively. These results indicate the feasibility of integrating radiomics analysis with deep learning for predicting EGFR mutations. CT-image-based genetic testing is a simple EGFR mutation prediction method, which can improve the prognosis of NSCLC patients and help establish personalized treatment strategies.

Objectives We aimed to develop an automated method for measuring the volume of the psoas muscle using CT to aid sarcopenia research efficiently.Methods We used a data set comprising the CT scans of 520 participants who underwent health check-ups at a health promotion centre. We developed a psoas muscle segmentation model using deep learning in a three-step process based on the nnU-Net method. The automated segmentation method was evaluated for accuracy, reliability, and time required for the measurement.Results The Dice similarity coefficient was used to compare the manual segmentation with automated segmentation; an average Dice score of 0.927 ± 0.019 was obtained, with no critical outliers. Our automated segmentation system had an average measurement time of 2 min 20 s ± 20 s, which was 48 times shorter than that of the manual measurement method (111 min 6 s ± 25 min 25 s).Conclusion We have successfully developed an automated segmentation method to measure the psoas muscle volume that ensures consistent and unbiased estimates across a wide range of CT images.

Abstract Preoperative templating needs to be precise to optimize hip arthroplasty outcomes. Unexpected implant mismatches can occur despite meticulous planning. We investigated the risk factors for oversized and undersized stem mismatch during uncemented hemiarthroplasty using a double-tapered wedge rectangular stem for femoral neck fracture. Out of 154 consecutive patients who underwent hemiarthroplasty for femoral neck fracture, 104 patients were divided into three groups: (1) oversized (n = 17; 16.3%), (2) matched (n = 80; 76.9%), and (3) undersized stem group (n = 7; 6.7%). A smaller femoral head offset (odds ratio [OR] = 0.89, 95% confidence interval [95% CI] = 0.81–0.98, P = 0.017), smaller isthmus diameter (OR = 0.57, 95% CI = 0.35–0.92, P = 0.021), and smaller canal flare index (OR = 0.20, 95% CI = 0.04–0.98, P = 0.047) were significantly associated with oversized stem insertion, while older age (OR = 1.18, 95% CI = 1.01–1.39, P = 0.037) was associated with undersized stem insertion in logistic regression. In conclusion, when performing hemiarthroplasty for a femoral neck fracture with a double-tapered wedge rectangular stem, surgeons must pay close attention to proximal femoral geometry and patient age during preoperative planning to avoid stem mismatch.

Abstract Few studies have found an association between statin use and head and neck cancer (HNC) outcomes. We examined the effect of statin use on HNC recurrence using the converted Observational Medical Outcome Partnership (OMOP) Common Data Model (CDM) in seven hospitals between 1986 and 2022. Among the 9,473,551 eligible patients, we identified 4669 patients with HNC, of whom 398 were included in the target cohort, and 4271 were included in the control cohort after propensity score matching. A Cox proportional regression model was used. Of the 4669 patients included, 398 (8.52%) previously received statin prescriptions. Statin use was associated with a reduced rate of 3- and 5-year HNC recurrence compared to propensity score-matched controls (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.61–1.03; and RR 0.89; 95% CI 0.70–1.12, respectively). Nevertheless, the association between statin use and HNC recurrence was not statistically significant. A meta-analysis of recurrence based on subgroups, including age subgroups, showed similar trends. The results of this propensity-matched cohort study may not provide a statistically significant association between statin use and a lower risk of HNC recurrence. Further retrospective studies using nationwide claims data and prospective studies are warranted.

Abstract The purpose of this study was to compare the periprosthetic bone mineral density (BMD) changes in the patients who underwent bipolar hemiarthroplasty (BPHA) for geriatric femoral neck fracture between two major different types of cementless femoral stems. A total of 93 patients (96 hips) who underwent BPHA for femoral neck fracture were categorized into two groups: Type 1 (42 patients, 44 hips), and Type 3C stem (51 patients, 52 hips). We investigated the annual follow-up trends of periprosthetic BMD at each Gruen zone during minimum postoperative 5-years; moreover, we compared the trends of periprosthetic BMD between both groups. The mean follow-up period was 7.1 years. In both groups, the overall BMD at the last follow-up had decreased compared with the baseline. In those with the Type 1 stem, BMD in the lateral femoral meta-diaphysis significantly decreased at 1-year follow-up after surgery. In those with Type 3C stem, BMD in the lateral femoral metaphysis postoperatively decreased after 3-years, whereas the BMD in the mediolateral femoral diaphysis drastically decreased postoperative 1-year period and plateaued thereafter. Different tendencies according to stem design were observed obviously in the postoperative BMD change of the proximal femur in patients who underwent BPHA for geriatric femoral neck fracture.

Abstract Background Chemical fertilizers have greatly contributed to the development of agriculture, but alternative fertilizers are needed for the sustainable development of agriculture. 2,3-butanediol (2,3-BDO) is a promising biological plant growth promoter. Results In this study, we attempted to develop an effective strategy for the biological production of highly pure R,R-2,3-butanediol (R,R-2,3-BDO) by Paenibacillus polymyxa fermentation. First, gamma-ray mutagenesis was performed to obtain P. polymyxa MDBDO, a strain that grew faster than the parent strain and had high production of R,R-2,3-BDO. The activities of R,R-2,3-butanediol dehydrogenase and diacetyl reductase of the mutant strain were increased by 33% and decreased by 60%, respectively. In addition, it was confirmed that the carbon source depletion of the fermentation broth affects the purity of R,R-2,3-BDO through batch fermentation. Fed-batch fermentation using controlled carbon feeding led to production of 77.3 g/L of R,R-2,3-BDO with high optical purity (> 99% of C4 products) at 48 h. Additionally, fed-batch culture using corn steep liquor as an alternative nitrogen source led to production of 70.3 g/L of R,R-2,3-BDO at 60 h. The fed-batch fermentation broth of P. polymyxa MDBDO, which contained highly pure R,R-2,3-BDO, significantly stimulated the growth of soybean and strawberry seedlings. Conclusions This study suggests that P. polymyxa MDBDO has potential for use in biological plant growth promoting agent applications. In addition, our fermentation strategy demonstrated that high-purity R,R-2,3-BDO can be produced at high concentrations using P. polymyxa.

Enzalutamide (ENZ), marketed under the brand name Xtandi® as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ’s low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development.

Head and neck squamous cell carcinomas (HNSCCs) undergo a stepwise progression from normal tissues. In order to better understand the molecular mechanisms behind such progression, here the authors profile HNSCC tumors at different stages using single-cell RNA-seq, and observe the role of interactions with the tumor microenvironment.

Abstract The skin functions as the outermost protective barrier to the internal organs and major vessels; thus, delayed regeneration from acute injury could induce serious clinical complications. For rapid recovery of skin wounds, promoting re-epithelialization of the epidermis at the initial stage of injury is essential, wherein epithelial keratinocytes act as leading cells via migration. This study applied plasma technology, which has been known to enable wound healing in the medical field. Through in vitro and in vivo experiments, the study elucidated the effect and molecular mechanism of the liquid plasma (LP) manufactured by our microwave plasma system, which was found to improve the applicability of existing gas-type plasma on skin cell migration for re-epithelialization. LP treatment promoted the cytoskeletal transformation of keratinocytes and migration owing to changes in the expression of integrin-dependent focal adhesion molecules and matrix metalloproteinases (MMPs). This study also identified the role of increased levels of intracellular reactive oxygen species (ROS) as a driving force for cell migration activation, which was regulated by changes in NADPH oxidases and mitochondrial membrane potential. In an in vivo experiment using a murine dorsal full-thickness acute skin wound model, LP treatment helped improve the re-epithelialization rate, reaffirming the activation of the underlying intracellular ROS-dependent integrin-dependent signaling molecules. These findings indicate that LP could be a valuable wound management material that can improve the regeneration potential of the skin via the activation of migration-related molecular signaling within the epithelial cell itself with plasma-driven oxidative eustress.

Abstract Background To support the sustainability of biodiesel production, by-products, such as crude glycerol, should be converted into high-value chemical products. 1,2-propanediol (1,2-PDO) has been widely used as a building block in the chemical and pharmaceutical industries. Recently, the microbial bioconversion of lactic acid into 1,2-PDO is attracting attention to overcome limitations of previous biosynthetic pathways for production of 1,2-PDO. In this study, we examined the effect of genetic engineering, metabolic engineering, and control of bioprocess factors on the production of 1,2-PDO from lactic acid by K. pneumoniae GEM167 with flux enhancement of the oxidative pathway, using glycerol as carbon source. Results We developed K. pneumoniae GEM167ΔadhE/pBR-1,2PDO, a novel bacterial strain that has blockage of ethanol biosynthesis and biosynthesized 1,2-PDO from lactic acid when glycerol is carbon source. Increasing the agitation speed from 200 to 400 rpm not only increased 1,2-PDO production by 2.24-fold to 731.0 ± 24.7 mg/L at 48 h but also increased the amount of a by-product, 2,3-butanediol. We attempted to inhibit 2,3-butanediol biosynthesis using the approaches of pH control and metabolic engineering. Control of pH at 7.0 successfully increased 1,2-PDO production (1016.5 ± 37.3 mg/L at 48 h), but the metabolic engineering approach was not successful. The plasmid in this strain maintained 100% stability for 72 h. Conclusions This study is the first to report the biosynthesis of 1,2-PDO from lactic acid in K. pneumoniae when glycerol was carbon source. The 1,2-PDO production was enhanced by blocking the synthesis of 2,3-butanediol through pH control. Our results indicate that K. pneumoniae GEM167 has potential for the production of additional valuable chemical products from metabolites produced through oxidative pathways.

Abstract Background Handgrip strength (HGS) has been adopted as one of the diagnostic tools for sarcopenia and is gaining attention because of its association with osteoporotic hip fractures. Longitudinal data of HGS at multiple follow-up intervals in older hip fractures are lacking. We aimed to investigate and compare the HGS changes in patients with hip fracture within 1-year with those in patients with hip diseases. Methods This prospective study was conducted between June 2018 and July 2020. The HGS was measured preoperatively, at predischarge, and at 3, 6, and 12 months postoperatively. We prospectively compared the number of patients with low muscle strength (LMS) as well as the HGS changes over time between the two groups. Results A total of 115 consecutive patients with hip fracture (n = 58) and hip disease (57) were enrolled. The rate of preoperative LMS was higher in the hip fracture group than control (P = 0.005), but there was no significant difference in the postoperative period (P = 0.343). The mean HGS was lower in the hip fracture group at all measured time periods. The preoperative HGS increased right before discharge (15.2 kg to 17.0 kg), and plateaued thereafter 1-year in the fracture group, whereas there were no statistically significant changes in serial follow-up trends in the control group. Conclusions The preoperative HGS in fracture patients may have been underestimated, due to different position of the arm, insufficient practice, or pain. Subsequently, HGS was rather constant during 1-year indicating no development of general sarcopenia after treatment for hip fracture. Therefore, in hip fracture patients, the predischarge HGS might be more reliable than preoperative HGS.

Abstract Background The quality of reduction is an important factor affecting clinical outcomes for displaced femoral neck fractures (FNFs). However, concerns remain about the invasiveness of open reduction and internal fixation (ORIF) as compared to that of closed reduction and internal fixation (CRIF), and the choice between ORIF and CRIF as an optimal treatment strategy for displaced pediatric FNF remains controversial. Materials and Methods MEDLINE, Embase, and the Cochrane Library were systematically searched for studies published up to December 22, 2022, that compared ORIF and CRIF techniques for treating FNF in children. Pooled analysis identified differences in surgical outcomes between ORIF and CRIF, especially regarding postoperative complications, such as osteonecrosis of the femoral head (ONFH), nonunion, coxa vara deformity, leg-length discrepancy LLD, and premature physeal closure (PPC). Results We included 15 studies with 635 pediatric FNF cases in our review. Of these, 324 and 311 were treated with ORIF and CRIF, respectively. The pooled analysis revealed that no significant differences existed between each reduction technique for ONFH (odds ratio [OR] = 0.89; 95% confidence interval [CI] 0.51–1.56; P = 0.69), nonunion (OR = 0.51; 95% CI 0.18–1.47; P = 0.21), coxa vara deformity (OR = 0.58; 95% CI 0.20–1.72; P = 0.33), LLD (OR = 0.57; 95% CI 0.18–1.82; P = 0.35), and PPC (OR = 0.72; 95% CI 0.11–4.92; P = 0.74). Conclusions Despite concerns about the invasiveness of ORIF, no differences in complications exist between ORIF and CRIF after FNF in children. Therefore, we believe that ORIF should be performed in FNF when the fracture is irreducible by closed manner.

Abstract Objectives Our aim in this study was to investigate if we could predict perforator localization during ALTF elevation, using information from acoustic Doppler (AD) and computed tomography angiography (CTA). Methods Prospective observational data were collected from H&N cancer patients who received reconstruction with ALTF in Ajou University Hospital Cancer Center from June to December, 2021. Total of 21 cases were included in the analysis. Lower extremity angio‐CT scans were used to determine the course and depth of the perforator before surgery. During intraoperative design of the ALTF, the possible location of the perforator was identified by AD. After flap elevation, the distance between the actual and Doppler‐identified location of the perforator was measured. Results The average distance from the actual location to the Doppler‐identified location was 1.29 ± 1.26 cm. Among 21 cases, almost all perforators (20 cases) were identified in a circle with a radius equivalent to the depth of the perforator. Perforator depth measured by CTA showed a significant positive correlation with the distance from the actual to Doppler‐identified location, regardless of skin thickness or body mass index (BMI). Conclusions A circle with a radius equivalent to the CTA‐assessed depth of the perforator successfully predicted the location of the perforator in almost all cases. Depth of the perforator measured by CTA combined with Doppler‐identified location can help safely locate the perforator during ALTF harvesting. Level of Evidence: 4.

Abstract Handgrip strength (HGS) now draws attention as one of the predictors of outcomes following geriatric hip fracture; however, its effectiveness and the optimal time to assess HGS remain unknown. Herein, we aimed to determine the usefulness of HGS in predicting the outcomes of geriatric hip fracture and to find the most effective time to measure HGS in both the low muscle strength and normal hip fracture groups. The study was performed prospectively for 79 geriatric hip fracture patients. HGS was measured during the admission period and the one-week postoperative period. Walking ability and quality of life were assessed using Koval scores and the European Quality of Life Five Dimension (EQ-5D) scale at the admission period and postoperatively at 3, 6, and 12 months, respectively. The relationship between pre/postoperative HGS and functional outcomes was assessed, and the functional score between the “low muscle strength” and “normal muscle strength” groups was compared. The association between HGS asymmetry and low strength with functional limitations was determined. For the preoperative HGS, the Koval score showed a significant relationship in the postoperative 6-month (r = −0.295, P = 0.008) and 12-month (r = −0.266, P = 0.019) periods; also, the EQ-5D score showed a significant relationship in the postoperative 6-month and 12-month periods (r = 0.344, P

Abstract Immunotherapy has a number of advantages over traditional anti-tumor therapy but can cause severe adverse reactions due to an overactive immune system. In contrast, a novel metabolic treatment approach can induce metabolic vulnerability through multiple cancer cell targets. Here, we show a therapeutic effect by inducing nucleotide imbalance and apoptosis in triple negative breast cancer cells (TNBC), by treating with cytosolic thymidylate 5'-phosphohydrolase (CT). We show that a sustained consumption of dTMP by CT could induce dNTP imbalance, leading to apoptosis as tricarboxylic acid cycle intermediates were depleted to mitigate this imbalance. These cytotoxic effects appeared to be different, depending on substrate specificity of the 5′ nucleotide or metabolic dependency of the cancer cell lines. Using representative TNBC cell lines, we reveal how the TNBC cells were affected by CT-transfection through extracellular acidification rate (ECAR)/oxygen consumption rate (OCR) analysis and differential transcription/expression levels. We suggest a novel approach for treating refractory TNBC by an mRNA drug that can exploit metabolic dependencies to exacerbate cell metabolic vulnerability.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) can lead to pulmonary dysfunction that is associated with pulmonary inflammation. Moreover, little is known regarding the therapeutic role of exercise training on pulmonary pathophysiology in NAFLD. The present study aimed to investigate the effect of exercise training on high-fat high-carbohydrate (HFHC)-induced pulmonary dysfunction in C57BL/6 mice. Methods Male C57BL/6 mice (N = 40) were fed a standard Chow (n = 20) or an HFHC (n = 20) diet for 15 weeks. After 8 weeks of dietary treatment, they were further assigned to 4 subgroups for the remaining 7 weeks: Chow (n = 10), Chow plus exercise (Chow+EX, n = 10), HFHC (n = 10), or HFHC plus exercise (HFHC+EX, n = 10). Both Chow+EX and HFHC+EX mice were subjected to treadmill running. Results Chronic exposure to the HFHC diet resulted in obesity with hepatic steatosis, impaired glucose tolerance, and elevated liver enzymes. The HFHC significantly increased fibrotic area (p < 0.001), increased the mRNA expression of TNF-α (4.1-fold, p < 0.001), IL-1β (5.0-fold, p < 0.001), col1a1 (8.1-fold, p < 0.001), and Timp1 (6.0-fold, p < 0.001) in the lung tissue. In addition, the HFHC significantly altered mitochondrial function (p < 0.05) along with decreased Mfn1 protein levels (1.8-fold, p < 0.01) and increased Fis1 protein levels (1.9-fold, p < 0.001). However, aerobic exercise training significantly attenuated these pathophysiologies in the lungs in terms of ameliorating inflammatory and fibrogenic effects by enhancing mitochondrial function in lung tissue (p < 0.001). Conclusions The current findings suggest that exercise training has a beneficial effect against pulmonary abnormalities in HFHC-induced NAFLD through improved mitochondrial function.

Abstract Background This study aimed to compare the clinical outcomes and complications between two minimally invasive surgical techniques: percutaneous transiliac plate fixation and iliosacral (IS) screw fixation for the treatment of Tile C-type pelvic bone fractures. Methods We retrospectively reviewed the data of 77 consecutive patients with Tile C pelvic ring injuries who underwent either percutaneous transiliac plate fixation or IS screw fixation in a single academic center between November 2007 and January 2018. We recorded patients’ demographics, surgery-related data, and postoperative surgical outcomes and compared the incidence of complications and revision surgery rates between the two groups. Results Overall, 14 patients were included in the plate group, while 63 were included in the IS screw fixation group. No significant differences were observed in the patients’ demographics between the two groups except for a longer interval from injury to surgery (13.5 days vs. 5.4 days, P = 0.001). Both groups acquired fracture union in all cases. There was one case of infection requiring surgical debridement in the plating group. Notably, nerve injury (n = 3) and implant loosening (n = 5) occurred in the IS screw group, but the difference was not significant. Conclusions Both percutaneous posterior transiliac plating and IS screw fixation in patients with Tile C-type pelvic bone fractures showed good results. We recommend IS screw fixation as the primary treatment and propose posterior plating as treatment for sacral dysmorphism and bilateral sacral alar fractures in patients with spinopelvic dissociation. Level of evidence III

Background/Aims The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrence Methods Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed. Results TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010). Conclusions The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.

Abstract In this study, we developed a deep learning model to identify patients with tongue cancer based on a validated dataset comprising oral endoscopic images. We retrospectively constructed a dataset of 12,400 verified endoscopic images from five university hospitals in South Korea, collected between 2010 and 2020 with the participation of otolaryngologists. To calculate the probability of malignancy using various convolutional neural network (CNN) architectures, several deep learning models were developed. Of the 12,400 total images, 5576 images related to the tongue were extracted. The CNN models showed a mean area under the receiver operating characteristic curve (AUROC) of 0.845 and a mean area under the precision-recall curve (AUPRC) of 0.892. The results indicate that the best model was DenseNet169 (AUROC 0.895 and AUPRC 0.918). The deep learning model, general physicians, and oncology specialists had sensitivities of 81.1%, 77.3%, and 91.7%; specificities of 86.8%, 75.0%, and 90.9%; and accuracies of 84.7%, 75.9%, and 91.2%, respectively. Meanwhile, fair agreement between the oncologist and the developed model was shown for cancer diagnosis (kappa value = 0.685). The deep learning model developed based on the verified endoscopic image dataset showed acceptable performance in tongue cancer diagnosis.

Abstract Background Redirecting pre-existing virus-specific cytotoxic CD8+ T lymphocytes (CTLs) to tumors by simulating a viral infection of the tumor cells has great potential for cancer immunotherapy. However, this strategy is limited by lack of amenable method for viral antigen delivery into the cytosol of target tumors. Here, we addressed the limit by developing a CD8+ T cell epitope-delivering antibody, termed a TEDbody, which was engineered to deliver a viral MHC-I epitope peptide into the cytosol of target tumor cells by fusion with a tumor-specific cytosol-penetrating antibody. Methods To direct human cytomegalovirus (CMV)-specific CTLs against tumors, we designed a series of TEDbodies carrying various CMV pp65 antigen-derived peptides. CMV-specific CTLs from blood of CMV-seropositive healthy donors were expanded for use in in vitro and in vivo experiments. Comprehensive cellular assays were performed to determine the presentation mechanism of TEDbody-mediated CMV peptide-MHC-I complex (CMV-pMHCI) on the surface of target tumor cells and the recognition and lysis by CMV-specific CTLs. In vivo CMV-pMHCI presentation and antitumor efficacy of TEDbody were evaluated in immunodeficient mice bearing human tumors. Results TEDbody delivered the fused epitope peptides into target tumor cells to be intracellularly processed and surface displayed in the form of CMV-pMHCI, leading to disguise target tumor cells as virally infected cells for recognition and lysis by CMV-specific CTLs. When systemically injected into tumor-bearing immunodeficient mice, TEDbody efficiently marked tumor cells with CMV-pMHCI to augment the proliferation and cytotoxic property of tumor-infiltrated CMV-specific CTLs, resulting in significant inhibition of the in vivo tumor growth by redirecting adoptively transferred CMV-specific CTLs. Further, combination of TEDbody with anti-OX40 agonistic antibody substantially enhanced the in vivo antitumor activity. Conclusion Our study offers an effective technology for MHC-I antigen cytosolic delivery. TEDbody may thus have utility as a therapeutic cancer vaccine to redirect pre-existing anti-viral CTLs arising from previously exposed viral infections to attack tumors.

Abstract Skin antiseptics have important implications for public health and medicine. Although conventional antiseptics have considerable antimicrobial activity, skin toxicity and the development of resistance are common problems. Plasma-treated water has sterilization and tissue-regenerative effects. Therefore, the aim of this study was to identify whether plasma-activated water (PAW) manufactured by our microwave plasma system can be used as a novel antiseptic solution for skin protection. PAW was produced by dissolving reactive nitrogen oxide gas using microwave plasma in deionized water. The antibacterial effects of PAW against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus, and Salmonella typhimurium and effective concentrations were investigated by a solid agar plate assay. The factors mediating the effects of PAW were evaluated by the addition of reactive species scavengers. Cytotoxicity and cell viability assays were performed to examine the protective effect of PAW on normal skin cells. PAW exhibited excellent sterilization and no toxicity in normal skin cells. Experiments also confirmed the potential of PAW as a sanitizer for SARS-CoV-2. Our findings support the use of PAW as an effective skin disinfectant with good safety in the current situation of a global pandemic.

Abstract This study aimed to investigate the spatial distribution and clinical significance of podoplanin expression in the metastatic lymph nodes of oropharyngeal squamous cell carcinomas (OPSCCs). The immunohistochemical podoplanin expression in the metastatic lymph nodes was evaluated in the pathologic specimens of 47 consecutive OPSCC patients. Clinicopathologic factors, including podoplanin expression and extranodal extension (ENE) status, were analyzed. Podoplanin was significantly expressed in the perinodal stroma (p = 0.001), and the average score of podoplanin was higher (p = 0.008) in ENE-positive lymph nodes than ENE-negative lymph nodes, although intranodal podoplanin expression did not differ significantly between the groups. Multivariable analysis revealed perinodal podoplanin expression as an independent marker of ENE in all the patients and the human papilloma virus (HPV)-positive group (p = 0.007 and p = 0.018, respectively). Podoplanin is differentially expressed in the metastatic lymph nodes in OPSCC, and its expression in perinodal stroma is associated with ENE, suggesting that podoplanin can be used clinically as a diagnostic biomarker.

Background and Objectives: Intravenous (IV) non-opioid analgesics (NOAs) have been extensively investigated as a multimodal analgesic strategy for the management of acute pain after hip surgery. This pair-wise meta-analysis examined IV NOA effects following hip surgery. Materials and Methods: A systematic search of the MEDLINE (PUBMED), Embase, and Cochrane Library databases was performed for studies investigating the effect of IV NOA for postoperative pain management following hip surgery up to 7 June 2023. We compared in-admission opioid use, postoperative VAS (visual analogue scale) score, hospital stay duration, and opioid-related adverse events between IV NOA and control groups. Results: Seven studies were included with a total of 953 patients who underwent hip surgery. Of these, 478 underwent IV NOA treatment, and 475 did not. The IV NOA groups had lower opioid use within 24-h following hip surgery (SMD, −0.48; 95% CI, −0.66 to −0.30; p < 0.01), lower VAS score (SMD, −0.47; 95% CI, −0.79 to −0.16; p < 0.01), shorter hospital stay (SMD, −0.28; 95% CI, −0.44 to −0.12; p < 0.01), and lower incidence of nausea and vomiting (OR, 0.32; 95% CI, 0.15 to 0.67; p < 0.01) compared with the control groups. Conclusions: This meta-analysis demonstrated that IV NOA administration following hip surgery may have more favorable postoperative outcomes than those in control groups.

Abstract Objective Doppler ultrasonography of the common carotid artery is used to infer stroke volume change and a wearable Doppler ultrasound has been designed to improve this workflow. Previously, in a human model of hemorrhage and resuscitation comprising approximately 50,000 cardiac cycles, we found a strong, linear correlation between changing stroke volume, and measures from the carotid Doppler signal, however, optimal Doppler thresholds for detecting a 10% stroke volume change were not reported. In this Research Note, we present these thresholds, their sensitivities, specificities and areas under their receiver operator curves (AUROC). Results Augmentation of carotid artery maximum velocity time integral and corrected flowtime by 18% and 4%, respectively, accurately captured 10% stroke volume rise. The sensitivity and specificity for these thresholds were identical at 89% and 100%. These data are similar to previous investigations in healthy volunteers monitored by the wearable ultrasound.

Abstract Purpose We aimed to compare the outcomes and complications of anatomical shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA) for primary glenohumeral osteoarthritis with intact cuff tissue. Materials and methods The MEDLINE, Embase, and Cochrane Library databases were systematically searched for studies published before March 2, 2021 using the PRISMA guidelines. Studies were included if they directly compared aTSA and rTSA for treating primary glenohumeral arthritis. A meta-analysis was performed using six studies that compared radiologic outcomes, functional scores, and range of motion (ROM). All the data were pooled using a random-effects model. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated as dichotomous data, while continuous data were analyzed using mean differences with 95% CIs. Results Two independent researchers reviewed 1,061 studies. Six studies met the inclusion criteria. The range of motion, especially external rotation, was better for aTSA than for rTSA (MD = − 10.28, 95% CI: − 16.69 to − 3.88, P = 0.002). Functional scores showed no difference between aTSA and rTSA. Glenoid loosening (OR = 0.17, 95% CI: 0.06–0.50, P = 0.001) was more common with aTSA, and scapula notching (OR = 10.63, 95% CI: 1.73–65.27, P = 0.01) with rTSA. In the mid-term follow-up, the overall revision rate showed no difference between aTSA and rTSA, with a pooled OR of 0.33 (95% CI: 0.07–1.57, P = 0.16). Conclusion A better ROM was achieved after aTSA than after rTSA. There was no difference in the revision rate at mid-term follow-up between aTSA and rTSA. Glenoid loosening was more common with aTSA, and scapula notching with rTSA. Level of evidence: Level IV, Meta-analysis.

Abstract Despite being the gold standard for diagnosis of osteoporosis, dual-energy X-ray absorptiometry (DXA) could not be widely used as a screening tool for osteoporosis. This study aimed to predict osteoporosis via simple hip radiography using deep learning algorithm. A total of 1001 datasets of proximal femur DXA with matched same-side cropped simple hip bone radiographic images of female patients aged ≥ 55 years were collected. Of these, 504 patients had osteoporosis (T-score ≤ − 2.5), and 497 patients did not have osteoporosis. The 1001 images were randomly divided into three sets: 800 images for the training, 100 images for the validation, and 101 images for the test. Based on VGG16 equipped with nonlocal neural network, we developed a deep neural network (DNN) model. We calculated the confusion matrix and evaluated the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We drew the receiver operating characteristic (ROC) curve. A gradient-based class activation map (Grad-CAM) overlapping the original image was also used to visualize the model performance. Additionally, we performed external validation using 117 datasets. Our final DNN model showed an overall accuracy of 81.2%, sensitivity of 91.1%, and specificity of 68.9%. The PPV was 78.5%, and the NPV was 86.1%. The area under the ROC curve value was 0.867, indicating a reasonable performance for screening osteoporosis by simple hip radiography. The external validation set confirmed a model performance with an overall accuracy of 71.8% and an AUC value of 0.700. All Grad-CAM results from both internal and external validation sets appropriately matched the proximal femur cortex and trabecular patterns of the radiographs. The DNN model could be considered as one of the useful screening tools for easy prediction of osteoporosis in the real-world clinical setting.

Background and Objectives: The anterior-based muscle-sparing (ABMS) approach, which utilizes the interval between the tensor fasciae latae posteriorly, offers several advantages, such as the reduced risk of nerve injury and the freedom to choose various implants. Herein, we aimed to compare the outcome of ABMS to the direct anterior (DA) approach using pairwise meta-analysis techniques. Materials and Methods: A systematic search of the MEDLINE (PUBMED), Embase, and Cochrane Library databases was performed for studies published up to 7 June 2023, which compared the ABMS approach with the DA approach for hip arthroplasty. We compared (1) perioperative outcomes (operation time, visual analog scale (VAS) score, total opioid consumption, length of hospital stay (LOS), and the number of patients discharged to their homes); (2) postoperative complications (neuropraxia/nerve injury, dislocation, surgical site infection, intraoperative fracture, and reoperation rate); and (3) implant position (cup inclination, cup anteversion, and stem alignment). Results: Ten studies were eligible for meta-analysis, including 1737 patients who underwent hip arthroplasty with the ABMS approach and 1979 with the DA approach. The pooled analysis showed no differences in all outcome variables, including perioperative outcomes, postoperative complications, and the implant position between the two surgical approaches. Conclusions: In current meta-analysis, the ABMS approach demonstrated comparable results to the conventional DA approach in terms of both clinical and radiologic outcomes as well as postoperative complications. Furthermore, the ABMS approach has the advantage of a broader indication and fewer limitations in terms of the surgical position compared to the DA approach. Therefore, the ABMS approach can be even more beneficial as an option within MSA, surpassing the utility of the DA approach.

Abstract Although the obesity paradox is an important modifiable factor in cardiovascular diseases, little research has been conducted to determine how it affects post-stroke cognitive function. We aimed to investigate the association between body mass index (BMI) and domain-specific cognitive outcomes, focusing on the subdivision of each frontal domain function in post-ischemic stroke survivors. A total of 335 ischemic stroke patients were included in the study after completion of the Korean-Mini Mental Status Examination (K-MMSE) and the vascular cognitive impairment harmonization standards neuropsychological protocol at 3 months after stroke. Frontal lobe functions were analyzed using semantic/phonemic fluency, processing speed, and mental set shifting. Our study participants were categorized into four groups according to BMI quartiles. The z-scores of K-MMSE at 3 months differed significantly between the groups after adjustment for initial stroke severity (p = 0.014). Global cognitive function in stroke survivors in the Q1 (the lowest quartile) BMI group was significantly lower than those in Q2 and Q4 (the highest quartile) BMI groups (K-MMSE z-scores, Q1: − 2.10 ± 3.40 vs. Q2: 0.71 ± 1.95 and Q4: − 1.21 ± 1.65). Controlled oral word association test findings indicated that phonemic and semantic word fluency was lower in Q4 BMI group participants than in Q2 BMI group participants (p = 0.016 and p = 0.023 respectively). BMI might differentially affect cognitive domains after ischemic stroke. Although being underweight may negatively affect global cognition post-stroke, obesity could induce frontal lobe dysfunctions, specifically phonemic and semantic word fluency.

Silk is a promising biomaterial for injectable hydrogel, but its long-gelation time and cytotoxic crosslinking methods are the main obstacles for clinical application. Here, we purpose a new in situ crosslinking technique of silk-alginate (S-A) injectable hydrogel using liquid-type non-thermal atmospheric plasma (LTP) in vocal fold (VF) wound healing. We confirmed that LTP induces the secondary structure of silk in a dose-dependent manner, resulting in improved mechanical properties. Significantly increased crosslinking of silk was observed with reduced gelation time. Moreover, controlled release of nitrate, an LTP effectors, from LTP-treated S-A hydrogel was detected over 7 days. In vitro experiments regarding biocompatibility showed activation of fibroblasts beyond the non-cytotoxicity of LTP-treated S-A hydrogels. An in vivo animal model of VF injury was established in New Zealand White rabbits. Full-thickness injury was created on the VF followed by hydrogel injection. In histologic analyses, LTP-treated S-A hydrogels significantly reduced a scar formation and promoted favorable wound healing. Functional analysis using videokymography showed eventual viscoelastic recovery. The LTP not only changes the mechanical structures of a hydrogel, but also has sustained biochemical effects on the damaged tissue due to controlled release of LTP effectors, and that LTP-treated S-A hydrogel can be used to enhance wound healing after VF injury.

Objectives Head and neck squamous cell carcinomas (HNSCs) are frequently diagnosed at the locoregional advanced stage (stage IVa), but controversy remains regarding whether stage IVa HSNCs should be treated with upfront surgery or definitive chemoradiation therapy (CRT). The purpose of this study was to compare overall survival (OS) and disease-free survival (DFS) in patients with stage IVa HNSC treated primarily by surgery with curative intent with/without (neo)adjuvant treatment (surgery group) versus those treated primarily with CRT (CRT group). Methods We reviewed data of 1,033 patients with stage IVa HNSC treated with curative intent at 17 cancer centers between 2010 and 2016. Results Among 1,033 patients, 765 (74.1%) received upfront surgery and 268 (25.9%) received CRT. The 5-year OS and DFS rates were 64.4% and 62.0% in the surgery group and 49.5% and 45.4% in the CRT group, respectively. In multivariate analyses, OS and DFS were better in the surgery group than in the CRT group (odds ratio [OR] for death, 0.762; 95% confidence interval [CI], 0.592–0.981; OR for recurrence, 0.628; 95% CI, 0.492–0.802). In subgroup analyses, the OS and DFS of patients with oropharyngeal cancer were better in the surgery group (OR for death, 0.548; 95% CI, 0.341–0.879; OR for recurrence, 0.598; 95% CI, 0.377–0.948). In the surgery group, patients with laryngeal cancer showed better OS (OR for death, 0.432; 95% CI, 0.211–0.882), while those with hypopharyngeal cancer DFS was improved (OR for recurrence, 0.506; 95% CI, 0.328–0.780). Conclusion A survival benefit from surgery may be achieved even in patients with stage IVa HNSC, particularly those with oropharyngeal and laryngeal cancer. Surgery led to a reduction in the recurrence rate in patients with hypopharyngeal cancer.

Background and Objectives:: There were limited studies which investigated nail diameter as a predictor for cephalomedullary nail (CMN) failure in intertrochanteric fracture (ITF). We aimed to evaluate the surgical outcomes of CMN in fragility ITF following nail–canal (N–C) diameter discordance. Materials and Methods: From November 2010 to March 2022, we retrospectively reviewed 120 consecutive patients who underwent CMN surgeries due to fragility ITF. We included patients with acceptable reduction and a tip–apex distance ≤ 25 mm. The N–C diameter differences both in anterior–posterior (AP) and lateral-view X-rays were measured, and we compared the number of excessive sliding instances and the rate of implant failure between the N–C concordance (≤3 mm) and discordance (>3 mm) group. Simple linear regression was used to determine the strength of the relationship between the N–C difference and sliding distance. Results: The sliding distance showed no differences between the groups in the AP (3.6 vs. 3.3 mm, p = 0.75) and lateral view (3.5 vs. 3.4 mm, p = 0.91). For analyses in the AP view, the AP-concordance and AP-discordance groups had 14 (25%) and 14 patients (22%) with a sliding distance of >5 mm (p = 0.69), while treatment failure occurred in 3 (5%) and 3 (3%) patients, respectively (p = 0.66). For analyses in the lateral view, the lat-concordance and lat-discordance groups had 8 (27%) and 20 patients (22%) with a sliding distance of >5 mm (p = 0.62), while treatment failure occurred in 1 (3%) and 4 (4%) patients, respectively (p = 1.00). Linear regression analyses showed that the N–C difference in either views was not a significant predictor of sliding distance in both the AP (R2 = 0.002, p = 0.60) and lateral views (R2 = 0.007, p = 0.35). Conclusions: If appropriate fracture reduction and fixation are achieved, the N–C discordance of short CMN does not affect treatment outcomes in ITF.

Background and Objectives: An acetabular reinforcement ring (ARR) with a structural allograft is conventionally used to treat large acetabular bone defects or discontinuity during revision hip arthroplasty. However, ARR is prone to failure due to bone resorption and lack of incorporation. Here, we investigated the surgical outcomes of the patients who underwent revision total hip arthroplasty (THA) using ARR combined with a metal augment (MA). Materials and Methods: We retrospectively reviewed data from 10 consecutive patients who had a minimum 8-year follow-up after revision hip arthroplasty using ARR with MA in Paprosky type III acetabular defect. We collected patient demographics, surgical details, clinical scores (including Harris Hip Score (HHS)), postoperative complications, and 8-year survival rates. Results: Six male and four female patients were included. The mean age was 64.3 years, and the mean follow-up duration was 104.3 months (96.0–112.0 months). Trauma-related diagnosis was the most common reason for index surgery. Three patients underwent all component revision, and seven underwent cup revision. Six were confirmed as Paprosky type IIIA and four as type IIIB. The mean HHS at the final follow-up was 81.5 (72–91). One patient was diagnosed with prosthetic joint infection at the 3-month follow-up; therefore, the minimum 8-year survival rate with our technique was 90.0% (95% confidence interval, 90.3–118.5%). Conclusions: The satisfactory mid- to long-term results of revision THA suggest that ARR combined with tantalum MA is a viable revision option for treating severe acetabular defects with pelvic discontinuity.

A wireless, wearable Doppler ultrasound offers a new paradigm for linking physiology to resuscitation medicine. To this end, the image analysis of simultaneously-acquired venous and arterial Doppler spectrograms attained by wearable ultrasound represents a new source of hemodynamic data. Previous investigators have reported a direct relationship between the central venous pressure (CVP) and the ratio of the internal jugular-to-common carotid artery diameters. Because Doppler power is directly related to the number of red cell scatterers within a vessel, we hypothesized that (1) the ratio of internal jugular-to-carotid artery Doppler power (V/APOWER) would be a surrogate for the ratio of the vascular areas of these two vessels and (2) the V/APOWER would track the anticipated CVP change during simulated hemorrhage and resuscitation. To illustrate this proof-of-principle, we compared the change in V/APOWER obtained via a wireless, wearable Doppler ultrasound to B-mode ultrasound images during a head-down tilt. Additionally, we elucidated the change in the V/APOWER during simulated hemorrhage and transfusion via lower body negative pressure (LBNP) and release. With these Interesting Images, we show that the Doppler V/APOWER ratio qualitatively tracks anticipated changes in CVP (e.g., cardiac preload) which is promising for both diagnosis and management of hemodynamic unrest.