An overview of immune checkpoint inhibitor toxicities in bladder cancer.

Bladder cancer is the tenth most prevalent malignancy worldwide, with a significant mortality burden. Urothelial carcinoma (UC) is the most common histological subtype, and treatment options are guided by whether the disease is muscle-invasive (MIBC) or non-muscle-invasive (NMIBC), with subsequent risk group stratification. The growing popularity of immune checkpoint inhibitors (ICIs) to treat MIBC and NMIBC as either monotherapy or combined with intravesical agents, may radically change the treatment paradigm of UC. Current treatments for NMBIC includes intravesical chemotherapy after trans-urethral resection of the bladder tumour, intravesical bacillus Calmette-Guerin (BCG) or radical cystectomy. Cisplatin-based chemotherapy is widely regarded as the first-line treatment for metastatic UC due to its beneficial response and survival rates when compared to alternative therapies. However, up to 70 % of metastatic UC patients are ineligible, and the prognosis of these patients remains poor, with a median survival of 13-16 months. For NMIBC and MIBC, ICIs provide a promising alternative for cisplatin-ineligible patients. In UC, ICIs including atezolizumab, nivolumab, avelumab, and pembrolizumab are Food and Drug Administration (FDA)-approved for monotherapy, and have demonstrated promising results, particularly in those who cannot receive cisplatin-based chemotherapy, and as a second-line treatment option for recurrent UC following platinum-based chemotherapy. It is important to consider that some patients may experience adverse events (AEs) with limited clinical benefit. Infusion-related reactions and immune-mediated AEs (imAEs) such as colitis, endocrinopathies, hepatitis, pneumonitis, interstitial lung disease, renal dysfunction, nephritis, cutaneous and neurological toxicities must be monitored for. Currently, there is no clear consensus on the role of a 'two-year stopping rule' in reducing the risk of imAEs, with further research on the optimal treatment duration of ICIs required. With increased ICI use, vigilance regarding their side effects is imperative. This review aims to provide an updated overview of ICI toxicities in bladder cancer, to assist clinicians in their therapeutic decision-making, with consideration of patient characteristics and the clinical context.

A deep learning approach to dysphagia-aspiration detecting algorithm through pre- and post-swallowing voice changes.

Introduction: This study aimed to identify differences in voice characteristics and changes between patients with dysphagia-aspiration and healthy individuals using a deep learning model, with a focus on under-researched areas of pre- and post-swallowing voice changes in patients with dysphagia. We hypothesized that these variations may be due to weakened muscles and blocked airways in patients with dysphagia. Methods: A prospective cohort study was conducted on 198 participants aged >40 years at the Seoul National University Bundang Hospital from October 2021 to February 2023. Pre- and post-swallowing voice data of the participants were converted to a 64-kbps mp3 format, and all voice data were trimmed to a length of 2 s. The data were divided for 10-fold cross-validation and stored in HDF5 format with anonymized IDs and labels for the normal and aspiration groups. During preprocessing, the data were converted to Mel spectrograms, and the EfficientAT model was modified using the final layer of MobileNetV3 to effectively detect voice changes and analyze pre- and post-swallowing voices. This enabled the model to probabilistically categorize new patient voices as normal or aspirated. Results: In a study of the machine-learning model for aspiration detection, area under the receiver operating characteristic curve (AUC) values were analyzed across sexes under different configurations. The average AUC values for males ranged from 0.8117 to 0.8319, with the best performance achieved at a learning rate of 3.00e-5 and a batch size of 16. The average AUC values for females improved from 0.6975 to 0.7331, with the best performance observed at a learning rate of 5.00e-5 and a batch size of 32. As there were fewer female participants, a combined model was developed to maintain the sex balance. In the combined model, the average AUC values ranged from 0.7746 to 0.7997, and optimal performance was achieved at a learning rate of 3.00e-5 and a batch size of 16. Conclusion: This study evaluated a voice analysis-based program to detect pre- and post-swallowing changes in patients with dysphagia, potentially aiding in real-time monitoring. Such a system can provide healthcare professionals with daily insights into the conditions of patients, allowing for personalized interventions. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05149976.

Evaluation of the efficacy and safety of Yukwool-tang for major depressive disorder in women: A randomized, double blinded, placebo-controlled, parallel trial.

BACKGROUND: Major depressive disorder (MDD) occurs more often in women than that in men due to various complex causes. This study aimed to evaluate the effectiveness and safety of Yukwool-tang (YWT) for MDD in women. METHODS: A total of 72 patients diagnosed with MDD and Korean version of the Hamilton Depression Rating Scale (K-HDRS) ≥ 14 points were randomly assigned to the YWT or placebo group, and 1 bottle (30 mg) of No-S solution and placebo was administered to the YWT and placebo groups, respectively, orally thrice a day for 8 weeks. The evaluation was conducted through K-HDRS, Korean version of the Beck Depression Inventory (BDI-K), Korean version of the Beck Hopelessness Scale (K-BHS), Korean version of the Insomnia Severity Index (ISI-K), State-Trait Anxiety Inventory (STAI-K), EuroQol-5 dimension (EQ-5D), and Pattern Identifications Tool for Depression (PITD). Fifty patients completed the trial. RESULTS: In the YWT group, the K-HDRS, BDI-K, K-BHS, ISI-K, STAI-K, and EQ-5D scores changed significantly at the 8th week, but there were no significant differences with the placebo. In subgroup analysis, the K-BHS score with an initial K-HDRS score < 18 points was significantly decreased compared to placebo at the 12th week (P < .05). In the YWT group, the ratio of Stagnation of Liver Gi () was the highest, but Dual Deficiency of the Heart and Spleen () became the highest after administration, which was also the highest in the placebo group both before and after administration. CONCLUSION: YWT improved depression and accompanying symptoms in women with MDD, although it was not significant compared to placebo, and it might be effective in improving the degree of hopelessness. The effect of YWT will become relatively clear through further research that can overcome certain limitations.

Feasibility of Emotional Freedom Techniques in Patients with Posttraumatic Stress Disorder: a pilot study.

Objectives: Posttraumatic stress disorder (PTSD) is a prevalent mental health condition, and techniques using sensory stimulation in processing traumatic memories have gained attention. The Emotional Freedom Techniques (EFT) is a psychotherapy that combines tapping on acupoints with exposure to cognitive reframing. This pilot study aimed to assess the feasibility of EFT as a treatment for PTSD by answering the following research questions 1) What is the compliance and completion rate of patients with PTSD with regard to EFT protocol? Is the dropout rate reasonable? 2) Is the effect size of EFT protocol for PTSD sufficient to justify a future trial? Methods: Thirty participants diagnosed with PTSD were recruited. They received weekly EFT sessions for five weeks, in which they repeated a statement acknowledging the problem and accepting themselves while tapping the SI3 acupoint on the side of their hand. PTSD symptoms were evaluated using the PTSD Checklist for DSM-5 (PCL-5) before and after the intervention. Results: Of the 30 PTSD patients (mean age 34.1 ± 9.1, 80% female), 96.7% showed over 80% compliance to the EFT sessions, and 86.7% completed the entire study process. The mean PCL-5 total score decreased significantly after the intervention, with a large effect size (change from baseline -14.33 [95% CI -19.79, -8.86], p < 0.0001, d = 1.06). Conclusion: The study suggests that EFT is a feasible treatment for PTSD, with high session compliance and low dropout rates. The effect size observed in this study supports the need for a larger trial in the future to further investigate EFT as a treatment for PTSD. However, the lack of a control group and the use of a self-rated questionnaire for PTSD symptoms are limitations of this study. The findings of this pilot study can be used to plan a future trial.

Prediction of dysphagia aspiration through machine learning-based analysis of patients' postprandial voices.

BACKGROUND: Conventional diagnostic methods for dysphagia have limitations such as long wait times, radiation risks, and restricted evaluation. Therefore, voice-based diagnostic and monitoring technologies are required to overcome these limitations. Based on our hypothesis regarding the impact of weakened muscle strength and the presence of aspiration on vocal characteristics, this single-center, prospective study aimed to develop a machine-learning algorithm for predicting dysphagia status (normal, and aspiration) by analyzing postprandial voice limiting intake to 3 cc. METHODS: Conducted from September 2021 to February 2023 at Seoul National University Bundang Hospital, this single center, prospective cohort study included 198 participants aged 40 or older, with 128 without suspected dysphagia and 70 with dysphagia-aspiration. Voice data from participants were collected and used to develop dysphagia prediction models using the Multi-Layer Perceptron (MLP) with MobileNet V3. Male-only, female-only, and combined models were constructed using 10-fold cross-validation. Through the inference process, we established a model capable of probabilistically categorizing a new patient's voice as either normal or indicating the possibility of aspiration. RESULTS: The pre-trained models (mn40_as and mn30_as) exhibited superior performance compared to the non-pre-trained models (mn4.0 and mn3.0). Overall, the best-performing model, mn30_as, which is a pre-trained model, demonstrated an average AUC across 10 folds as follows: combined model 0.8361 (95% CI 0.7667-0.9056; max 0.9541), male model 0.8010 (95% CI 0.6589-0.9432; max 1.000), and female model 0.7572 (95% CI 0.6578-0.8567; max 0.9779). However, for the female model, a slightly higher result was observed with the mn4.0, which scored 0.7679 (95% CI 0.6426-0.8931; max 0.9722). Additionally, the other models (pre-trained; mn40_as, non-pre-trained; mn4.0 and mn3.0) also achieved performance above 0.7 in most cases, and the highest fold-level performance for most models was approximately around 0.9. The 'mn' in model names refers to MobileNet and the following number indicates the 'width_mult' parameter. CONCLUSIONS: In this study, we used mel-spectrogram analysis and a MobileNetV3 model for predicting dysphagia aspiration. Our research highlights voice analysis potential in dysphagia screening, diagnosis, and monitoring, aiming for non-invasive safer, and more effective interventions. TRIAL REGISTRATION: This study was approved by the IRB (No. B-2109-707-303) and registered on clinicaltrials.gov (ID: NCT05149976).

Topographical and crystalline change on surface by sandblasting improve flexural and shear bond strength of niobia-modified yttria-stabilized tetragonal zirconia polycrystal.

This study aimed to investigate the effects of sandblasting on the physical properties and bond strength of two types of translucent zirconia: niobium-oxide-containing yttria-stabilized tetragonal zirconia polycrystals ((Y, Nb)-TZP) and 5 mol% yttria-partially stabilized zirconia (5Y-PSZ). Fully sintered disc specimens were either sandblasted with 125 µm alumina particles or left as-sintered. Surface roughness, crystal phase compositions, and surface morphology were explored. Biaxial flexural strength (n=10) and shear bond strength (SBS) (n=12) were evaluated, including thermocycling conditions. Results indicated a decrease in flexural strength of 5Y-PSZ from 601 to 303 MPa upon sandblasting, while (Y, Nb)-TZP improved from 458 to 544 MPa. Both materials significantly increased SBS after sandblasting (p<0.001). After thermocycling, (Y, Nb)-TZP maintained superior SBS (14.3 MPa) compared to 5Y-PSZ (11.3 MPa) (p<0.001). The study concludes that (Y, Nb)-TZP is preferable for sandblasting applications, particularly for achieving durable bonding without compromising flexural strength.

Association Between Taurine Level in the Hippocampus and Major Depressive Disorder in Young Women: A Proton Magnetic Resonance Spectroscopy Study at 7T.

BACKGROUND: Major depressive disorder (MDD) is characterized by depressed mood or loss of interest or pleasure. Generally, women are twice as likely as men to have depression. Taurine, a type of amino acid, plays critical roles in neuronal generation, differentiation, arborization, and formation of synaptic connections. Importantly, it enhances proliferation and synaptogenesis in the hippocampus. When injected into animals, taurine has an antidepressant effect. However, there is no in vivo evidence to show an association between taurine concentration in the human brain and the development of MDD. METHODS: Forty-one unmedicated young women with MDD (ages 18-29) and 43 healthy control participants matched for gender and age were recruited in South Korea. Taurine concentration was measured in the hippocampus, anterior cingulate cortex, and occipital cortex of the MDD and healthy control groups using proton magnetic resonance spectroscopy at 7T. Analysis of covariance was used to examine differences in taurine concentration, adjusting for age as a covariate. RESULTS: Taurine concentration in the hippocampus was lower (F1,75 = 5.729, p = .019, Δη2 = 0.073) for the MDD group (mean [SEM] = 0.91 [0.06] mM) than for the healthy control group (1.13 [0.06] mM). There was no significant difference in taurine concentration in the anterior cingulate cortex or occipital cortex between the two groups. CONCLUSIONS: This study demonstrates that a lower level of taurine concentration in the hippocampus may be a novel characteristic of MDD.

Frontiers of Ovarian Carcinosarcoma.

OPINION STATEMENT: Ovarian carcinosarcoma (OCS), also known as a malignant mixed Müllerian tumour (MMMT), is a rare and aggressive form of cancer that accounts for less than 5% of ovarian cancers. It is characterized by high morbidity and mortality rates, with a median overall survival (OS) of less than 2 years. Several factors, including advancing age, nulliparity, reduced lactation rates, decreased use of oral contraceptive pills, genetic mutations in BRCA (breast cancer) genes, and the use of assisted reproductive technology, may increase the risk of OCS. Poor prognostic factors include an advanced stage at diagnosis, older age, lymph node metastasis, suboptimal surgical cytoreduction, the presence of heterologous features on histopathology, and increased expression of vascular endothelial growth factor (VEGF), tumour protein p53, and p53 alongside Wilms tumour 1 (WT1). The main treatment approach for OCS is cytoreductive surgery followed by platinum-based chemotherapy, although immunotherapy is showing promise. Homologous recombination deficiency (HRD) testing may enhance outcomes by enabling personalized immunotherapy and targeted therapies for specific patient groups, thereby reducing unnecessary side effects and healthcare costs. However, there is currently a lack of standardised treatment regimens for OCS patients, with most studies consisting of case reports and a shortage of suitable comparator groups. This article aims to provide clinicians with information on the epidemiology, risk factors, prognostic factors, and latest therapeutic advancements in OCS.

Application of 3D scanner to measure physical size and improvement of hip brace manufacturing technology in severe cerebral palsy patients.

This prospective pilot study aimed to develop a personalized hip brace for treating hip subluxation in children with cerebral palsy. Nineteen children, aged 1-15, with severe cerebral palsy participated in the study. Customized hip braces were created based on 3D scanner measurements and worn for 7 days. The primary outcome, Hip Migration Index (MI), and secondary outcomes, including range of motion (ROM) in the hip and knee joints, pain intensity, satisfaction, discomfort scores, CPCHILD, and wearability test, were assessed. The MI and ROM were assessed at screening and at Visit 1 (when the new hip brace was first worn), while other indicators were evaluated at screening, Visit 1, and Visit 2 (7 days after wearing the new hip brace). The study demonstrated significant improvements in the MI for the right hip, left hip, and both sides. However, there were no statistically significant differences in hip and knee joint ROM. Other indicators showed significant changes between screening, Visit 1, and Visit 2. The study suggests that customized hip braces effectively achieved immediate correction, positively impacting the quality of life and satisfaction in children with cerebral palsy. Furthermore, the hip braces have the potential to enhance compliance and prevent hip subluxation.Clinical Trial Registration number: NCT05388422.

Cardiac Toxicities in Oncology: Elucidating the Dark Box in the Era of Precision Medicine.

Despite current advancements in chemotherapy, immunotherapy and targeted treatments, the potential for major adverse cardiovascular events, regardless of previous cardiac history, persists. Scoring systems, such as the Heart Failure Association-International Cardio-Oncology Society (HFA-ICOS) risk assessment tool, can be utilized to evaluate several factors including prior cardiac history, risk factors and cardiac biomarkers to categorize patients into low, moderate, high, and very high-risk groups. Common cardiotoxicity complications include new or worsening left ventricular ejection fraction (LVEF), QT interval prolongation, myocardial ischaemia, hypertension, thromboembolic disease, cardiac device malfunction and valve disease. Baseline electrocardiogram (ECG) and transthoracic echocardiogram (TTE) are routinely performed for all patients commenced on cardiotoxic treatment, while other imaging modalities and biochemical markers have proven useful for monitoring. Management mainly includes early risk stratification and prompt identification of cardiovascular complications, with patient-specific surveillance throughout treatment. A multidisciplinary approach is crucial in determining the relationship between potential treatment benefits and cardiotoxicity, and whether the continuation of treatment is appropriate on a case-by-case basis. Early risk stratification, optimizing the patient's cardiovascular status prior to treatment, and prompt identification of suspected cardiotoxicity are key in significantly reducing risk. This article provides a comprehensive review of the various types of treatment-related cardiotoxicity, offering guidance on identifying high-risk patients, recognizing early signs of cardiotoxicity, and outlining appropriate treatment approaches and follow-up care for such cases.

Antibacterial activity and biocompatibility of silver coating via aerosol deposition on titanium and zirconia surfaces.

PURPOSE: The purpose of this in vitro study was to investigate the antibacterial effect and biocompatibility of silver coatings via aerosol deposition on titanium and zirconia surfaces. METHODS: The surfaces of titanium and zirconia specimens were polished and coated with silver via aerosol deposition. After silver coating, the elemental composition, surface roughness and amount of silver released from the coated surfaces were measured. The bacterial growth on the silver-coated surfaces was investigated via crystal violet assay after incubation with Streptococcus gordonii for 24 h, Fusobacterium nucleatum for 72 h and Porphyromonas gingivalis for 48 h. Human gingival fibroblasts and mouse preosteoblasts were also cultured on the silver-coated specimens to examine the biocompatibility of the coating. RESULTS: After silver coating via aerosol deposition, the surface roughness increased significantly, and the released silver ranged from 0.067 to 0.110 ppm. The tested bacteria formed significantly less biofilm on the silver-coated titanium surfaces than on the uncoated titanium surfaces. In contrast, biofilm formation on the silver-coated zirconia surfaces was greater than that on the uncoated zirconia surfaces. Human gingival fibroblasts and mouse preosteoblasts proliferated on the silver-coated surfaces without significant differences from the uncoated surfaces. CONCLUSIONS: Silver coating via aerosol deposition provided an antibacterial effect against oral bacteria on titanium surfaces, whereas it promoted more bacterial growth on zirconia surfaces. The proliferation of fibroblasts and osteoblasts was not significantly affected by the silver coating on both titanium and zirconia surfaces.

Gestational Renal Cell Cancer - An Update.

Gestational renal cell carcinoma (RCC) is an uncommon occurrence and presents a diagnostic and clinical challenge for healthcare providers. The manifestation of gestational RCC often lacks overt symptoms and can mimic physiological changes and disorders associated with pregnancy. Frequently, patients are asymptomatic, and the condition is detected during routine antenatal ultrasonography. However, the options for imaging modalities and treatment are limited due to the potential risks of harm to the developing fetus and interruption of pregnancy. Throughout the management of pregnant patients with RCC, both maternal and neonatal risks must be carefully considered, while respecting the patient's autonomy. Currently, there are no internationally or nationally recognized evidence-based guidelines for managing gestational RCC, highlighting the need for a multidisciplinary approach to treatment. Advances in surgical techniques have resulted in a shift from open surgeries to laparoscopic radical or partial nephrectomy procedures, with robotic-assisted approaches also gaining popularity. In cases of metastatic gestational RCC, termination of the pregnancy may be considered, and the appropriate treatment of RCC should be the priority. This article aims to provide a comprehensive review of the epidemiology, aetiology, clinical presentation, diagnosis, prognosis, and management of gestational RCC.

Emotional freedom technique versus written exposure therapy versus waiting list for post-traumatic stress disorder: protocol for a randomised clinical MRI study.

INTRODUCTION: The emotional freedom technique (EFT) is an acupuncture-based psychotherapy that combines tapping on acupoints with cognitive reframing. EFT has been previously shown to have potential for treating post-traumatic stress disorder (PTSD). However, further clinical evidence and underlying mechanisms of EFT are yet to be fully explored. This proposed clinical trial aims to examine the effect of EFT on patients with PTSD compared with the waitlist (WL) and active controls. METHODS AND ANALYSIS: This study was designed as a randomised, assessor-blinded, three-arm clinical MRI study. A total of 120 eligible patients with PTSD will be recruited and randomised into EFT, written exposure therapy (WET) or WL groups. EFT and WET will be applied once a week for 5 weeks. For patients in the WL group, EFT will be performed after 12 weeks. PTSD symptoms, depression, anxiety, somatic symptoms and quality of life will be evaluated. Assessments will be conducted at baseline (week 0), post-treatment (week 6) and follow-up (week 12). Structural and functional brain images and recording videos of facial expressions to emotional stimuli will be obtained before and after treatment. Sixty participants without lifetime traumatic experiences will be enrolled as healthy controls. The primary objective of the study is to compare the change from baseline in the Clinician-Administered PTSD Scale after treatment (week 6) between EFT and WL groups and between EFT and WET groups. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Review Board of the Kyung Hee University Korean Medicine Hospital. The research findings will be shared at national and international conferences and will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Clinical Research Information Service KCT0007360 https://cris.nih.go.kr/cris/search/detailSearch.do/21974.

The effect of surface material, roughness and wettability on the adhesion and proliferation of Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis.

Background/purpose: Dental implants are inevitably exposed to bacteria in oral cavity. Understanding the colonization of bacteria on implant surface is necessary to prevent bacteria-related inflammation surrounding dental implants. The purpose of this study was to investigate the effect of surface properties on biofilm formation on the implant surface. Materials and methods: One early colonizer, Streptococcus gordonii (S. gordonii), and two late colonizers, Fusobacterium nucleatum (F. nucleatum) and Porphyromonas gingivalis (P. gingivalis), were grown on the titanium and zirconia surfaces with two types of surface roughness for 24 and 72 h. Each bacterial biofilm on specimens was quantified using crystal violet assay and observed by scanning electron microscopy. Results: S. gordonii formed more biofilm on the titanium surface than zirconia at the same roughness and more biofilm on the rough surface than smooth one of the same materials at 24 and 72 h of incubation. F. nucleatum adhered on all the surfaces at 24 h and proliferated actively on the surfaces except smooth zirconia at 72 h. P. gingivalis proliferated vigorously on the surfaces at 72 h while it scarcely adhered at 24 h. There was no consistent correlation between contact angle and biofilm formation of the three bacteria. Conclusion: The three bacteria proliferated most on the rough titanium surface and least on the smooth zirconia surface. In addition, the proliferation was affected by the bacterial species as well as the surface properties.

Attenuated facial movement in depressed women is associated with symptom severity, and nucleus accumbens functional connectivity.

It is assumed that mood can be inferred from one's facial expression. While this association may prove to be an objective marker for mood disorders, few studies have explicitly evaluated this linkage. The facial movement responses of women with major depressive disorder (n = 66) and healthy controls (n = 46) under emotional stimuli were recorded using webcam. To boost facial movements, the naturalistic audio-visual stimuli were presented. To assess consistent global patterns across facial movements, scores for facial action units were extracted and projected onto principal component using principal component analysis. The associations of component for facial movements with functional brain circuitry was also investigated. Clusters of mouth movements, such as lip press and stretch, identified by principal component analysis, were attenuated in depressive patients compared to those in healthy controls. This component of facial movements was associated with depressive symptoms, and the strengths of resting brain functional connectivity between nucleus accumbens and both posterior insular cortex and thalamus. The evaluation of facial movements may prove to be a promising quantitative marker for assessing depressive symptoms and their underlying brain circuitry.

HPV and Cervical Cancer: A Review of Epidemiology and Screening Uptake in the UK.

Cervical cancer is the fourth most common malignancy in females worldwide, and a leading cause of death in the United Kingdom (UK). The human papillomavirus (HPV) is the strongest risk factor for developing cervical intraepithelial neoplasia and cancer. Across the UK, the national HPV immunisation programme, introduced in 2008, has been successful in protecting against HPV-related infections. Furthermore, the National Health Service (NHS) implemented the cytology-based cervical cancer screening service to all females aged 25 to 64, which has observed a decline in cervical cancer incidence. In the UK, there has been an overall decline in age-appropriate coverage since April 2010. In 2019, the COVID-19 pandemic disrupted NHS cancer screening and immunisation programmes, leading to a 6.8% decreased uptake of cervical cancer screening from the previous year. Engagement with screening has also been associated with social deprivation. In England, incidence rates of cervical cancer were reported to be 65% higher in the most deprived areas compared to the least, with lifestyle factors such as cigarette consumption contributing to 21% of cervical cancer cases. In this article, we provide an update on the epidemiology of cervical cancer, and HPV pathogenesis and transmission, along with the current prevention programmes within the NHS.

Evaluating Different Quantitative Shear Wave Parameters of Ultrasound Elastography in the Diagnosis of Lymph Node Malignancies: A Systematic Review and Meta-Analysis.

Shear wave elastography (SWE) has shown promise in distinguishing lymph node malignancies. However, the diagnostic accuracies of various SWE parameters that quantify tissue stiffness are yet to be demonstrated. To evaluate the pooled diagnostic accuracy of different SWE parameters for differentiating lymph node malignancies, we conducted a systematic screening of four databases using the PRISMA guidelines. Lymph node biopsy was adopted as the reference standard. Emax (maximum stiffness), Emean (mean stiffness), Emin (minimum stiffness), and Esd (standard deviation) SWE parameters were subjected to separate meta-analyses. A sub-group analysis comparing the use of Emax in cervical (including thyroid) and axillary lymph node malignancies was also conducted. Sixteen studies were included in this meta-analysis. Emax and Esd demonstrated the highest pooled sensitivity (0.78 (95% CI: 0.69-0.87); 0.78 (95% CI: 0.68-0.87)), while Emean demonstrated the highest pooled specificity (0.93 (95% CI: 0.88-0.98)). From the sub-group analysis, the diagnostic performance did not differ significantly in cervical and axillary LN malignancies. In conclusion, SWE is a promising adjunct imaging technique to conventional ultrasonography in the diagnosis of lymph node malignancy. SWE parameters of Emax and Esd have been identified as better choices of parameters for screening clinical purposes.

The Human Skin Volatolome: A Systematic Review of Untargeted Mass Spectrometry Analysis.

The analysis of volatile organic compounds (VOCs) can provide important clinical information (entirely non-invasively); however, the exact extent to which VOCs from human skin can be signatures of health and disease is unknown. This systematic review summarises the published literature concerning the methodology, application, and volatile profiles of skin VOC studies. An online literature search was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis, to identify human skin VOC studies using untargeted mass spectrometry (MS) methods. The principal outcome was chemically verified VOCs detected from the skin. Each VOC was cross-referenced using the CAS number against the Human Metabolome and KEGG databases to evaluate biological origins. A total of 29 studies identified 822 skin VOCs from 935 participants. Skin VOCs were commonly sampled from the hand (n = 9) or forearm (n = 7) using an absorbent patch (n = 15) with analysis by gas chromatography MS (n = 23). Twenty-two studies profiled the skin VOCs of healthy subjects, demonstrating a volatolome consisting of aldehydes (18%), carboxylic acids (12%), alkanes (12%), fatty alcohols (9%), ketones (7%), benzenes and derivatives (6%), alkenes (2%), and menthane monoterpenoids (2%). Of the VOCs identified, 13% had putative endogenous origins, 46% had tentative exogenous origins, and 40% were metabolites from mixed metabolic pathways. This review has comprehensively profiled the human skin volatolome, demonstrating the presence of a distinct VOC signature of healthy skin, which can be used as a reference for future researchers seeking to unlock the clinical potential of skin volatolomics. As significant proportions of identified VOCs have putative exogenous origins, strategies to minimise their presence through methodological refinements and identifying confounding compounds are discussed.

Fracture Resistance of Monolithic Zirconia Crowns Depending on Different Marginal Thicknesses.

Under some clinical conditions, the preparation of crowns of limited marginal thickness is inevitable. In such situations, it is questionable whether the same ideal preparation criteria can be applied equally. Since there are only a small number of studies focusing on the fracture resistance with respect to the marginal thickness, there is a need for a study evaluating whether zirconia crowns of limited marginal thickness are clinically acceptable. The purpose of this study is to evaluate the fracture resistance of monolithic zirconia crowns of limited marginal thickness in the posterior area. Methods: Abutments and CAD/CAM zirconia crowns with a marginal thickness of 1.0 mm were set as the control group, while experimental groups A, B, and C possessed reduced marginal thicknesses of 0.8 mm, 0.6 mm, and 0.4 mm, respectively (n = 10 per group). Resin-based abutment dies and monolithic zirconia crowns were fabricated using the CAD/CAM technique, and a universal testing machine was used to measure the fracture load value. Fractured specimens were examined with a scanning electron microscope. The data were analyzed using a one-way ANOVA and Bonferroni post hoc test (p < 0.05). Results: The means and standard deviations of the fracture load values of the control group and the three experimental groups were as follows: control group (1.0 mm): 3090.91 ± 527.77 N; group A (0.8 mm): 2645.39 ± 329.21 N; group B (0.6 mm): 2256.85 ± 454.15 N; group C (0.4 mm): 1957.8 ± 522.14 N. Conclusions: The crowns fabricated with a CAD/CAM zirconia block with limited marginal thicknesses of 0.6 mm and 0.4 mm showed significantly lower fracture resistance values compared to those with the recommended margin thickness of 1.0 mm.

Characterization of the Secretome of a Specific Cell Expressing Mutant Methionyl-tRNA Synthetase in Co-Culture Using Click Chemistry.

Co-culture system, in which two or more distinct cell types are cultured together, is advantageous in that it can mimic the environment of the in vivo niche of the cells. In this study, we presented a strategy to analyze the secretome of a specific cell type under the co-culture condition in serum-supplemented media. For the cell-specific secretome analysis, we expressed the mouse mutant methionyl-tRNA synthetase for the incorporation of the non-canonical amino acid, azidonorleucine into the newly synthesized proteins in cells of which the secretome is targeted. The azidonorleucine-tagged secretome could be enriched, based on click chemistry, and distinguished from any other contaminating proteins, either from the cell culture media or the other cells co-cultured with the cells of interest. In order to have more reliable true-positive identifications of cell-specific secretory bodies, we established criteria to exclude any identified human peptide matched to bovine proteins. As a result, we identified a maximum of 719 secreted proteins in the secretome analysis under this co-culture condition. Last, we applied this platform to profile the secretome of mesenchymal stem cells and predicted its therapeutic potential on osteoarthritis based on secretome analysis.