Analysis of 5 years' experience of a head and neck surgeon with radiofrequency ablation for benign thyroid nodule.

PURPOSE: This study reports the long-term efficacy, safety, complications and management of radiofrequency ablation (RFA) for benign thyroid nodule performed over 5 years by a head and neck surgeon. MATERIALS AND METHODS: We studied 287 consecutive patients who underwent RFA between March 2011 and January 2021. Pre- and postoperative thyroid nodule volumes were measured and volume reduction rate was calculated using ultrasonography (USG). Subjective symptom scores and cosmetic scores were investigated. Complications and their managements were analyzed. Complications and their management were investigated. Follow-up USG was performed at 6 and 12 months after RFA, and annually thereafter. RESULTS: The mean volume reduction was 75.2 ± 23.8 % after 6 months and 91.9 ± 14.8 % after 5 years. All of nodule volume, and the cosmetic and symptom scores, decreased significantly postoperatively, and these scores were maintained to 5 years. Minor complications occurred in 15 of 287 (5.2 %) patients; there were no major complications. Injection laryngoplasty was performed for three patients with vocal cord paralysis. Two patients underwent open thyroid surgery because of nodule regrowth. CONCLUSIONS: RFA is a safe and effective treatment without major complication for more than five years. Minor complications were managed by the head-and-neck surgeon personally.

Ultrasound-guided hydrodilatation for adhesive capsulitis of the hip is a safe and effective treatment.

PURPOSE: Adhesive capsulitis of the hip (ACH) is likely that this condition had been previously encountered, but easily unrecognised. We investigated the clinical features of patients with ACH, the efficacy of ultrasound-guided intra-articular hydrodilatation, and the patients' prognosis. METHODS: We enrolled 84 patients (93 hips) who visited the outpatient clinic from August 2018 to November 2019. ACH was diagnosed by restricted range of motion and sharp pain when turning with the affected leg fixed on the ground. We evaluated patient demographics and associated intra-articular pathologies found on magnetic resonance angiography (MRA) images. Injections were performed twice at two week intervals with a mixture of 0.5% lidocaine (25 mL) and triamcinolone (40 mg; 1 mL) with capsular distension under ultrasound guidance. Patients were assessed before and after treatment using a visual analogue scale (VAS), hip disability and osteoarthritis outcome score (HOOS), hip range of motion (ROM), and distance from floor to knee (DFK) when sitting in the cross-legged position. RESULTS: On MRA, 18 patients had abnormal findings (eight labral tears, seven abductor tendinosis, three primary arthrosis). The mean VAS decreased from 7.1 ± 1.1 to 0.8 ± 0.9 after the last injection, and the HOOS improved in all subsets. The mean DFK decreased from 17.9 ± 4.8 to 9.7 ± 2.8 cm, and passive ROM showed improvement, especially in flexion and rotation. In seven patients, symptom recurrence was reported a mean of 4.1 months after the latest injection, but no independent risk factor for recurrence was identified. CONCLUSION: Based on these current observations, patients with ACH may receive relief from hip joint pain and experience improved function with a timely diagnosis and effective treatment.

The Preventive Effect of the Phenotype of Tumour-Associated Macrophages, Regulated by CD39, on Colon Cancer in Mice.

BACKGROUND: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. METHODS: An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting. RESULTS: In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group. CONCLUSION: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.

Improved Method for Reliable HMW-GS Identification by RP-HPLC and SDS-PAGE in Common Wheat Cultivars.

The accurate identification of alleles for high-molecular weight glutenins (HMW-GS) is critical for wheat breeding programs targeting end-use quality. RP-HPLC methods were optimized for separation of HMW-GS, resulting in enhanced resolution of 1By and 1Dx subunits. Statistically significant differences in retention times (RTs) for subunits corresponding to HMW-GS alleles were determined using 16 standard wheat cultivars with known HMW-GS compositions. Subunits that were not identified unambiguously by RP-HPLC were distinguished by SDS-PAGE or inferred from association with linked subunits. The method was used to verify the allelic compositions of 32 Korean wheat cultivars previously determined using SDS-PAGE and to assess the compositions of six new Korean cultivars. Three cultivars contained subunits that were identified incorrectly in the earlier analysis. The improved RP-HPLC method combined with conventional SDS-PAGE provides for accurate, efficient and reliable identification of HMW-GS and will contribute to efforts to improve wheat end-use quality.

Upconversion Nanoparticle-Based Förster Resonance Energy Transfer for Detecting DNA Methylation.

Aberrant methylation of a crucial CpG island is the main mechanism for the inactivation of CDKN2A in the early stages of carcinogenesis. Therefore, the detection of DNA methylation with high sensitivity and specificity is important, and various detection methods have been developed. Recently, upconversion nanoparticles (UCNPs) have been found to display a high signal-to-noise ratio and no photobleaching, making them useful for diagnostic applications. In this pilot study, we applied UCNPs to the detection of CDKN2A methylation and evaluated the feasibility of this system for use in molecular diagnostics. DNA PCR was performed using biotinylated primers, and the PCR amplicon was then intercalated with SYTOX Orange dye, followed by incubation with streptavidin-conjugated UCNPs. Fluorescence detection of the Förster resonance energy transfer (FRET) of the UCNPs (MS-UC-FRET) was then performed, and the results were compared to those from real-time PCR (RQ-PCR) and pyrosequencing. Detection by MS-UC-FRET was more sensitive than that by either RQ-PCR or pyrosequencing. Our results confirmed the success of our MS-UC-FRET system for detecting DNA methylation and demonstrated the potential application of this system in molecular diagnostics.

Volatile profiling of aromatic traditional medicinal plant, Polygonum minus in different tissues and its biological activities.

The aim of this research was to identify the volatile metabolites produced in different organs (leaves, stem and roots) of Polygonum minus, an important essential oil producing crop in Malaysia. Two methods of extraction have been applied: Solid Phase Microextraction (SPME) and hydrodistillation coupled with Gas Chromatography-Mass Spectrometry (GC-MS). Approximately, 77 metabolites have been identified and aliphatic compounds contribute significantly towards the aroma and flavour of this plant. Two main aliphatic compounds: decanal and dodecanal were found to be the major contributor. Terpenoid metabolites were identified abundantly in leaves but not in the stem and root of this plant. Further studies on antioxidant, total phenolic content, anticholinesterase and antimicrobial activities were determined in the essential oil and five different extracts. The plant showed the highest DPPH radical scavenging activity in polar (ethanol) extract for all the tissues tested. For anti-acetylcholinesterase activity, leaf in aqueous extract and methanol extract showed the best acetylcholinesterase inhibitory activities. However, in microbial activity, the non-polar extracts (n-hexane) showed high antimicrobial activity against Methicillin-resistant Staphylococcus aureus (MRSA) compared to polar extracts. This study could provide the first step in the phytochemical profiles of volatile compounds and explore the additional value of pharmacology properties of this essential oil producing crop Polygonum minus.

Validity of Modified STOP-Bang Questionnaire as a Screening Tool for Obstructive Sleep Apnea.

OBJECTIVES: The aim of this study was to evaluate the validity of a modified STOP-Bang questionnaire with different body mass index reference as a screening tool for obstructive sleep apnea in Korean population. METHODS: The medical records of 1417 participants who underwent overnight Level I polysomnography were retrospectively analyzed. Predictive parameters were calculated for each of the 3 groups classified by obstructive sleep apnea severity with a cut-off value of 3 or 4. Responses to modified and traditional questionnaires were comparatively analyzed by receiver-operator characteristic curves and area under the receiver-operator characteristic curves. RESULTS: The optimal cut-off values of the modified and traditional questionnaires were both 3.5. The area under the receiver-operator characteristic curve of modified STOP-Bang questionnaire for any obstructive sleep apnea group was 0.786 ± 0.018, which was significantly higher than that of the traditional questionnaire. The modified STOP-Bang questionnaire with a cut-off value ≥4 showed significantly higher sensitivity than the traditional one for any obstructive sleep apnea group. The diagnostic accuracy of the modified questionnaire was also significantly higher for the any obstructive sleep apnea group when the cut-off value was 4. CONCLUSION: The modified STOP-Bang questionnaire, with a cut-off value of 4, can be used as an alternative to the traditional screening tool for the Korean population.

Preoperative evaluation of systolic murmur with point-of-care echocardiography before an elective thoracic surgery - A case report.

BACKGROUND: Systolic murmur suggesting the association of aortic valve (AV) stenosis or obstructive pathology in the left ventricular outflow tract (LVOT) usually requires preoperative echocardiographic evaluation for elective surgery. CASE: In a 63-year-old female patient undergoing elective thoracic surgery, the systolic murmur was auscultated on the right sternal border of the second intercostal space in the preoperative patient holding area. Point-of-care (POC) transthoracic echocardiography (TTE) demonstrated a systolic jet flow in the LVOT area. The peak systolic velocity of the continuous wave Doppler tracing, aligned to the LVOT and the AV, was approximately 1.5 m/s. The peak/mean pressure gradient was 11/6 mmHg for the AV and 9/5 mmHg for the LVOT. Anesthesia was induced under continuous TTE imaging. Intraoperative transesophageal echocardiography also confirmed the absence of any cardiac pathology. CONCLUSIONS: POC echocardiography offered a thorough preoperative evaluation of an unexpectedly identified systolic murmur, avoiding a potential delay in the operation schedule for conventional preoperative echocardiographic evaluation.

Imputing missing sleep data from wearables with neural networks in real-world settings.

Sleep is a critical component of health and well-being but collecting and analyzing accurate longitudinal sleep data can be challenging, especially outside of laboratory settings. We propose a simple neural network model titled SOMNI (Sleep data restOration using Machine learning and Non-negative matrix factorIzation [NMF]) for imputing missing rest-activity data from actigraphy, which can enable clinicians to better handle missing data and monitor sleep-wake cycles of individuals with highly irregular sleep-wake patterns. The model consists of two hidden layers and uses NMF to capture hidden longitudinal sleep-wake patterns of individuals with disturbed sleep-wake cycles. Based on this, we develop two approaches: the individual approach imputes missing data based on the data from only one participant, while the global approach imputes missing data based on the data across multiple participants. Our models are tested with shift and non-shift workers' data from three independent hospitals. Both approaches can accurately impute missing data up to 24 hours of long dataset (>50 days) even for shift workers with extremely irregular sleep-wake patterns (AUC > 0.86). On the other hand, for short dataset (~15 days), only the global model is accurate (AUC > 0.77). Our approach can be used to help clinicians monitor sleep-wake cycles of patients with sleep disorders outside of laboratory settings without relying on sleep diaries, ultimately improving sleep health outcomes.

A comprehensive Exdia TRF-LFIA for simultaneous quantification of GFAP and NT-proBNP in distinguishing ischemic and hemorrhagic stroke.

The goal of this study is to create a highly sensitive time-resolved fluorescence lateral flow immunoassay (TRF-LFIA) capable of concurrently measuring glial fibrillary acidic protein (GFAP) and the N-terminal fragment of B-type natriuretic peptide precursor (NT-proBNP). This assay is designed as a diagnostic tool and aims to provide an algorithm for stroke management, specifically for distinguishing between Ischemic stroke (IS) and Hemorrhagic stroke (HS). However, LFIA to quantify simultaneous serum NT-proBNP and GFAP are not yet available. We have developed and validated a novel TRF-LFIA for the simultaneous quantitative detection of NT-proBNP and GFAP. The sensitivity and reproducibility of the immunoassay were significantly improved by employing specific monoclonal antibodies linked to europium nanoparticles (EuNPs) that specifically target NT-proBNP and GFAP. The detection area on the nitrocellulose membrane featured sandwich-style complexes containing two test lines for NT-proBNP and GFAP, and one Control line. The fluorescence intensity of these test lines and control line was measured using an in-house developed Exdia TRF-Plus analyzer. As proof-of-concept, we enrolled patients suspected of having a stroke who were admitted within a specific time frame (6 h). A small amount of clinical specimen (serum) was used. To optimize the LFIA, an EuNPs conjugated antibodies were investigated to improve the detection sensitivity and decrease the background signal as well shorten the detection time. The Exdia TRF-LFIA cartridge offers a wide linear dynamic detection range, rapid detection, high sensitivity, and specificity. The limit of detection was determined to be 98 pg/mL for NT-proBNP and 68 pg/mL for GFAP, with minimal cross-reactivity. There were 200 clinical human serum samples that were used to evaluate this platform with high correlation. By combining the results of NT-proBNP and GFAP, we formulated an algorithm for the clinical assessment of Ischemic Stroke (IS) and Hemorrhagic Stroke (HS). According to our proposed algorithm, the combination of GFAP and NT-proBNP emerged as the most effective biomarker combination for distinguishing between IS and HS. Exdia TRF-LFIA shows great potential as a supplemental method for in vitro diagnostics in the laboratory or in other point-of-care testing (POCT) applications. Its development substantially decreases the diagnosis time for IS and HS. The proposed algorithm not only minimizes treatment delays but also lowers medical costs for patients.

The Immune Suppressor IGSF1 as a Potential Target for Cancer Immunotherapy.

The development of first-generation immune-checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 ushered in a new era in anticancer therapy. Although immune-checkpoint blockade therapies have shown clinical success, a substantial number of patients yet fail to benefit. Many studies are under way to discover next-generation immunotherapeutic targets. Immunoglobulin superfamily member 1 (IGSF1) is a membrane glycoprotein proposed to regulate thyroid function. Despite containing 12 immunoglobin domains, a possible role for IGSF1, in immune response, remains unknown. Here, our studies revealed that IGSF1 is predominantly expressed in tumors but not normal tissues, and increased expression is observed in PD-L1low non-small cell lung cancer (NSCLC) cells as compared with PD-L1high cells. Subsequently, we developed and characterized an IGSF1-specific human monoclonal antibody, WM-A1, that effectively promoted antitumor immunity and overcame the limitations of first-generation immune-checkpoint inhibitors, likely via a distinct mechanism of action. We further demonstrated high WM-A1 efficacy in humanized peripheral blood mononuclear cells (PBMC), and syngeneic mouse models, finding additive efficacy in combination with an anti-PD-1 (a well-characterized checkpoint inhibitor). These findings support IGSF1 as an immune target that might complement existing cancer immunotherapeutics.

Speech quality estimation of voice over internet protocol codec using a packet loss impairment model.

This letter proposes a degradation and cognition model to estimate speech quality impairment because of packet loss concealment (PLC) algorithm implemented in the speech CODEC SILK. By considering the fact that the quality degradation caused by packet loss is highly related to the PLC algorithm, the impact of quality degradation on various types of previous and lost packet classes is analyzed. Then, the PLC effects to the proposed class types are measured by the class conditional expectation of the degradation scores. Finally, the cognition module is derived to estimate the total quality degradation in a mean opinion score (MOS) scale. When assessed for correlation with subject test results, the correlation coefficient of the encoder-based class model is 0.93, and that of the decoder-based model is 0.87.

Efficient assessment of real-world dynamics of circadian rhythms in heart rate and body temperature from wearable data.

Laboratory studies have made unprecedented progress in understanding circadian physiology. Quantifying circadian rhythms outside of laboratory settings is necessary to translate these findings into real-world clinical practice. Wearables have been considered promising way to measure these rhythms. However, their limited validation remains an open problem. One major barrier to implementing large-scale validation studies is the lack of reliable and efficient methods for circadian assessment from wearable data. Here, we propose an approximation-based least-squares method to extract underlying circadian rhythms from wearable measurements. Its computational cost is ∼ 300-fold lower than that of previous work, enabling its implementation in smartphones with low computing power. We test it on two large-scale real-world wearable datasets: [Formula: see text] of body temperature data from cancer patients and ∼ 184 000 days of heart rate and activity data collected from the 'Social Rhythms' mobile application. This shows successful extraction of real-world dynamics of circadian rhythms. We also identify a reasonable harmonic model to analyse wearable data. Lastly, we show our method has broad applicability in circadian studies by embedding it into a Kalman filter that infers the state space of the molecular clocks in tissues. Our approach facilitates the translation of scientific advances in circadian fields into actual improvements in health.

Discovery of Novel, Thienopyridine-Based Tyrosine Kinase Inhibitors Targeting Tumorigenic RON Splice Variants.

Herein, we report the identification, structural optimization, and biological efficacy of thieno[2,3-b]pyridines as potent inhibitors of splice variants of the tyrosine kinase recepteur d'origine nantais (RON). Among synthesized compounds, compound 15f exhibited excellent in vitro kinase inhibition and antiproliferative activity, as well as in vivo antineoplastic efficacy against RON splice variant-expressing tumors. Moreover, compound 15f with excellent pharmacokinetics demonstrated significant activity with greater tumor growth inhibition (74.9% at 10 mg/kg) than compounds 2 and 4 in a patient-derived xenograft model. Collectively, 15f represents a promising, novel anticancer agent targeting RON splice variants.

Targeting isoforms of RON kinase (MST1R) drives antitumor efficacy.

Recepteur d'origine nantais (RON, MST1R) is a single-span transmembrane receptor tyrosine kinase (RTK) aberrantly expressed in numerous cancers, including various solid tumors. How naturally occurring splicing isoforms of RON, especially those which are constitutively activated, affect tumorigenesis and therapeutic response, is largely unknown. Here, we identified that presence of activated RON could be a possible factor for the development of resistance against anti-EGFR (cetuximab) therapy in colorectal cancer patient tissues. Also, we elucidated the roles of three splicing variants of RON, RON Δ155, Δ160, and Δ165 as tumor drivers in cancer cell lines. Subsequently, we designed an inhibitor of RON, WM-S1-030, to suppress phosphorylation thereby inhibiting the activation of the three RON variants as well as the wild type. Specifically, WM-S1-030 treatment led to potent regression of tumor growth in solid tumors expressing the RON variants Δ155, Δ160, and Δ165. Two mechanisms for the RON oncogenic activity depending on KRAS genotype was evaluated in our study which include activation of EGFR and Src, in a trimeric complex, and stabilization of the beta-catenin. In terms of the immunotherapy, WM-S1-030 elicited notable antitumor immunity in anti-PD-1 resistant cell derived mouse model, likely via repression of M1/M2 polarization of macrophages. These findings suggest that WM-S1-030 could be developed as a new treatment option for cancer patients expressing these three RON variants.

Enhancing Mixing Performance in a Rotating Disk Mixing Chamber: A Quantitative Investigation of the Effect of Euler and Coriolis Forces.

Lab-on-a-CD (LOCD) is gaining importance as a diagnostic platform due to being low-cost, easy-to-use, and portable. During LOCD usage, mixing and reaction are two processes that play an essential role in biochemical applications such as point-of-care diagnosis. In this paper, we numerically and experimentally investigate the effects of the Coriolis and Euler forces in the mixing chamber during the acceleration and deceleration of a rotating disk. The mixing performance is investigated under various conditions that have not been reported, such as rotational condition, chamber aspect ratio at a constant volume, and obstacle arrangement in the chamber. During disk acceleration and deceleration, the Euler force difference in the radial direction causes rotating flows, while the Coriolis force induces perpendicular vortices. Increasing the maximum rotational velocity improves the maximum rotational displacement, resulting in better mixing performance. A longer rotational period increases the interfacial area between solutions and enhances mixing. Mixing performance also improves when there is a substantial difference between Euler forces at the inner and outer radii. Furthermore, adding obstacles in the angular direction also passively promotes or inhibits mixing by configuration. This quantitative investigation provides valuable information for designing and developing high throughput and multiplexed point-of-care LOCDs.

Expression of the human cancer/testis antigen NY-SAR-35 is activated by CpG island hypomethylation.

The novel cancer/testis antigen gene, NY-SAR-35, is expressed exclusively in normal testis and in various histological types of tumor. However, the NY-SAR-35 gene expression is observed to be aberrant in several cancer cell lines and tissues. The analysis of methylation status of the NY-SAR-35 gene promoter in various cancer cell lines showed that its expression was related to methylation of the promoter region. Treatment of human cancer cell lines with the demethylating agent 5-aza-2'-deoxycytidine activated the expression of the NY-SAR-35 gene. In addition, transfection experiments on various fragments of the CpG-rich gene promoter indicate that in vitro methylation of the NY-SAR-35 gene promoter results in the loss of promoter activity. The expression of NY-SAR-35 is therefore activated by hypomethylation of the CpG island in the gene promoter.

Dynamic contact angle measurements on lubricant infused surfaces.

HYPOTHESIS: Even though lubricant-infused surfaces (LISs) are known to affect the mobility of working fluid depending on the infused lubricant, previous studies have not yet quantified their slippery property. This study proposes the slippery nature of the LIS can be assessed by dynamic contact angles of the working fluid on the LIS and its scaling model. EXPERIMENTS: We measured the apparent dynamic advancing and receding contact angles on a LIS using a modified Wilhelmy plate technique for the first time. Lubricant having different viscosities was infused into the sanded polytetrafluoroethylene surface to fabricate the LIS. The surface was immersed into or withdrawn from an aqueous glycerol-water solution by varying the capillary number and the lubricant viscosity. FINDINGS: The dynamic contact angles on LIS was found to be sensitive to changes in both the lubricant viscosity and the capillary number. The cube of the dynamic contact angles on the LIS was proportional to θD3~Ca1, which follows a conventional hydrodynamic theory. In addition, the decreasing lubricant viscosity shifted the cube of the dynamic contact angles to high capillary numbers. Our dynamic contact angle data coincided with the prediction from a scaling law derived in this study.

Fixation of isolated Lisfranc ligament injury with the TightRope™: A technical report.

Treatment of Lisfranc ligament injury is still debatable. For this reason, we applied a standard suture button (TightRope™, Arthrex, Naples, FL), a device originally designed for syndesmosis fixation, in treating isolated Lisfranc ligament (ILL) injuries. Twelve patients diagnosed as having an ILL injury were recruited. All patients regained their previous activity level within 3 months after the surgery without any complications. We propose that standard suture button device in an ILL injury is an easy technique to perform with short learning curve, accompanied with satisfactory outcomes.

Cancer Testis Antigen, NOL4, Is an Immunogenic Antigen Specifically Expressed in Small-Cell Lung Cancer.

To identify cancer/testis (CT) antigens and immunogenic proteins, immunoscreening of testicular and small-cell lung cancer cell line NCI-H889 cDNA libraries was performed using serum obtained from a small-cell lung cancer (SCLC) patient. We obtained 113 positive cDNA clones comprised of 74 different genes, designated KP-SCLC-1 through KP-SCLC-74. Of these genes, 59 genes were found to be related to cancers by EMBASE analysis. Three of these antigens, including KP-SCLC-29 (NOL4), KP-SCLC-59 (CCDC83), and KP-SCLC-69 (KIF20B), were CT antigens. RT-PCR and western blot analysis showed that NOL4 was frequently present in small-cell lung cancer cell lines (8/9, 8/9). In addition, NOL4 mRNA was weakly, or at a low frequency, or not detected in various cancer cell lines. Our results reveal that NOL4 was expressed at protein levels in small-cell lung cancer tissues (10/10) but not detected in lung adenocarcinoma and squamous cell carcinoma by immunohistochemical analysis. Serological response to NOL4 was also evaluated by western blot assay using NOL4 recombinant protein. A humoral response against NOL4 proteins was detected in 75% (33/44) of small-cell lung cancer patients and in 65% (13/20) of healthy donors by a serological western blot assay. These data suggest that NOL4 is a specific target that may be useful for diagnosis and immunotherapy in SCLC.