Accuracy of artificial intelligence-assisted growth prediction in skeletal Class I preadolescent patients using serial lateral cephalograms for a 2-year growth interval.

OBJECTIVE: To investigate the accuracy of artificial intelligence-assisted growth prediction using a convolutional neural network (CNN) algorithm and longitudinal lateral cephalograms (Lat-cephs). MATERIALS AND METHODS: A total of 198 Japanese preadolescent children, who had skeletal Class I malocclusion and whose Lat-cephs were available at age 8 years (T0) and 10 years (T1), were allocated into the training, validation, and test phases (n = 161, n = 17, n = 20). Orthodontists and the CNN model identified 28 hard-tissue landmarks (HTL) and 19 soft-tissue landmarks (STL). The mean prediction error values were defined as 'excellent,' 'very good,' 'good,' 'acceptable,' and 'unsatisfactory' (criteria: 0.5 mm, 1.0 mm, 1.5 mm, and 2.0 mm, respectively). The degree of accurate prediction percentage (APP) was defined as 'very high,' 'high,' 'medium,' and 'low' (criteria: 90%, 70%, and 50%, respectively) according to the percentage of subjects that showed the error range within 1.5 mm. RESULTS: All HTLs showed acceptable-to-excellent mean PE values, while the STLs Pog', Gn', and Me' showed unsatisfactory values, and the rest showed good-to-acceptable values. Regarding the degree of APP, HTLs Ba, ramus posterior, Pm, Pog, B-point, Me, and mandibular first molar root apex exhibited low APPs. The STLs labrale superius, lower embrasure, lower lip, point of lower profile, B', Pog,' Gn' and Me' also exhibited low APPs. The remainder of HTLs and STLs showed medium-to-very high APPs. CONCLUSION: Despite the possibility of using the CNN model to predict growth, further studies are needed to improve the prediction accuracy in HTLs and STLs of the chin area.

Widening disparities in the national prevalence of diabetes mellitus for people with disabilities in South Korea.

OBJECTIVES: In Korea, diabetes mellitus has a high disease burden, based on disability-adjusted life years. However, the disease burden is disproportionately distributed, with people with disabilities (PWD) experiencing higher rates of health disparities. Our study investigated long-term trends in diabetes prevalence and risk according to disability status, grade, and type. STUDY DESIGN: Retrospective cohort study. METHODS: Approximately 10 million individuals aged ≥30 years were included yearly from the National Health Information Database (NHID) and national disability registration data in Korea between 2008 and 2017, corresponding to 40 % of those aged ≥30 years in Korea. In 2017, 12, 975, 757 individuals were included; 5.5 % had disabilities. We estimated annual diabetes age-standardized prevalence and used multiple logistic regression analyses to estimate the odds of having diabetes in 2017, according to disability status, severity, and type. RESULTS: Diabetes age-standardized prevalence consistently increased over 2008-2017 in PWD and people without disabilities. However, the prevalence increased more rapidly and was higher in all years among PWD, with widening disparities based on disability status. Additionally, diabetes prevalence was high in all years for specific subgroups, including women, individuals with intellectual or mental disabilities or autism, and individuals with severe disabilities, suggesting further disparities among PWD. CONCLUSIONS: Our findings reveal health disparities between those with and without disabilities and among PWD subgroups. In addition to timely prevention, diabetes screening and management among PWD is vital. Public investment in improving disparities in the root causes of diabetes is essential, including health behaviours, healthcare utilization, and self-care.

The cGAS-STING signaling pathway is modulated by urolithin A.

During aging, general cellular processes, including autophagic clearance and immunological responses become compromised; therefore, identifying compounds that target these cellular processes is an important approach to improve our health span. The innate immune cGAS-STING pathway has emerged as an important signaling system in the organismal defense against viral and bacterial infections, inflammatory responses to cellular damage, regulation of autophagy, and tumor immunosurveillance. These key functions of the cGAS-STING pathway make it an attractive target for pharmacological intervention in disease treatments and in controlling inflammation and immunity. Here, we show that urolithin A (UA), an ellagic acid metabolite, exerts a profound effect on the expression of STING and enhances cGAS-STING activation and cytosolic DNA clearance in human cell lines. Animal laboratory models and limited human trials have reported no obvious adverse effects of UA administration. Thus, the use of UA alone or in combination with other pharmacological compounds may present a potential therapeutic approach in the treatment of human diseases that involves aberrant activation of the cGAS-STING pathway or accumulation of cytosolic DNA and this warrants further investigation in relevant transgenic animal models.

Nationwide prevalence and trends in cigarette smoking among adult men with and without disabilities in South Korea between 2009 and 2017.

OBJECTIVES: Current smoking rates for people with and without disabilities vary among countries. This study analyzed smoking behavior over 9 years in adult South Korean men with disabilities, according to disability severity and type, and in those without disabilities. STUDY DESIGN: This was a cross-sectional study. METHODS: This analysis was conducted using national disability registration data and national general health checkup data for 2009-2017. Age-standardized smoking behaviors were analyzed for each year according to the presence, severity, and type of disability. The odds of current smoking were determined by multivariate logistic regression after adjusting for sociodemographic and clinical variables. RESULTS: The age-standardized smoking rate and average number of cigarettes for men with mild disabilities in the younger age group were 1.16 (43.0 vs 36.8%) and 1.05 (16.1 vs 15.3 cigarettes) times higher than in non-disabled men as of 2017. The highest smoking rate was observed in men with physical disabilities in the younger age. In the older age group, the highest smoking rate was that of men with intellectual or psychological disabilities. CONCLUSION: Smoking behaviors remained poorest in men with disabilities, especially those with mild, physical, and intellectual/psychological disabilities. Public health policies should focus on people with disabilities to promote health, prevent secondary conditions, and reduce health disparities by implementing antismoking health policies.

Impact of changes in clinical practice guidelines for intra-articular injection treatments for knee osteoarthritis on public interest and social media.

OBJECTIVE: To summarize changes in recommendations for injection treatments for knee osteoarthritis (OA) in current clinical practice guidelines (CPGs) and to assess whether these changes have affected public interest according to Google data and content in YouTube videos. DESIGN: A literature search to identify CPGs revised since 2019 that provide recommendations regarding the five intra-articular injection treatments for knee OA (corticosteroid [CS], hyaluronic acid [HA], stem cell [SC], platelet-rich plasma [PRP], and botulinum toxin [BT]) was conducted to assess perspective changes for each treatment. Data from Google Trends were examined to identify changes in search volume from 2004 to 2021 using a join-point regression model. Relevant YouTube videos were divided into those uploaded before and after changes in CPGs and compared according to degrees of recommendation for each treatment to identify the effect of changes in CPGs on video production. RESULTS: All eight identified CPGs released after 2019 recommended HA and CS use. Most CPGs were the first to state a neutral or opposing stance concerning the use of SC, PRP, or BT. Interestingly, relative searches on Google for SC, PRP, and BT has increased greater than those for CS and HA. YouTube videos produced after CPGs changed continue to recommend SC, PRP, and BT as much as those produced before CPGs were revised. CONCLUSIONS: Although knee OA CPGs have changed, public interest and healthcare information providers on YouTube have not reacted to this shift. Improved methods to propagate updates to CPGs warrant consideration.

The Glasgow Microenvironment Score and risk and site of recurrence in TNM I-III colorectal cancer.

BACKGROUND: Glasgow Microenvironment Score (GMS) stratifies long-term survival into three groups based on tumour phenotype: peritumoural inflammation (Klintrup-Mäkinen (KM)) and tumour stroma percentage (TSP). However, it is not known if the location of disease recurrence is influenced by the GMS category. METHODS: Seven hundred and eighty-three TNM I-III colorectal cancers (CRC) were included. GMS (GMS0-high KM; GMS1-low KM, low TSP; GMS2-low KM, high TSP) and cancer-specific survival (CSS), overall survival (OS) and disease recurrence were assessed using Cox regression analysis. RESULTS: Of the 783 patients, 221 developed CRC recurrence; 65 developed local recurrence + systemic disease. GMS was independent for CSS (HR 1.50, 95% CI 1.17-1.92, p < 0.001) and OS (HR 1.23, 1.05-1.44, p = 0.01). Higher GMS category was associated with T-stage, N-stage, emergency presentation and venous invasion. GMS was independent for local+systemic recurrence (HR 11.53, 95% CI 1.45-91.85, p = 0.04) and distant-only recurrence (HR 3.01, 95% CI 1.59-5.71, p = 0.002). GMS 2 disease did not appear to have statistically better outcomes with adjuvant chemotherapy in high-risk disease. CONCLUSION: Although confounded by a higher rate of T4 and node-positive disease, GMS 1 and 2 are associated with an increased risk of local and distant recurrence. GMS is an independent poor prognostic indicator for recurrent colorectal cancer. Higher GMS patients may benefit from enhanced postoperative surveillance.

Preoperative Chemoradiotherapy With Capecitabine With or Without Temozolomide in Patients With Locally Advanced Rectal Cancer: A Prospective, Randomised Phase II Study Stratified by O6-Methylguanine DNA Methyltransferase Status: KCSG-CO17-02.

AIMS: To evaluate the clinical efficacy of adding temozolomide (TMZ) to preoperative capecitabine (CAP)-based chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and validate O6-methylguanine DNA methyltransferase (MGMT) methylation status as a predictive marker for TMZ combined regimens. MATERIALS AND METHODS: LARC patients with clinical stage II (cT3-4N0) or III (cTanyN+) disease were enrolled. They were stratified into unmethylated MGMT (uMGMT) and methylated MGMT (mMGMT) groups by methylation-specific polymerase chain reaction before randomisation and were then randomly assigned (1:1) to one of four treatment arms: uMGMT/CAP (arm A), uMGMT/TMZ + CAP (arm B), mMGMT/CAP (arm C) and mMGMT/TMZ + CAP (arm D). The primary end point was the pathological complete response (pCR) rate. RESULTS: Between November 2017 and July 2020, 64 patients were randomised. Slow accrual caused early study termination. After excluding four ineligible patients, 60 were included in the full analysis set. The pCR rate was 15.0% (9/60), 0%, 14.3%, 18.8% and 26.7% for the entire cohort, arms A, B, C and D, respectively (P = 0.0498 between arms A and D). The pCR rate was 9.7% in the CAP group (arms A + C), 20.7% in the TMZ + CAP group (arms B + D), 6.9% in the uMGMT group (arms A + B) and 22.6% in the mMGMT group (arms C + D). Grade 1-2 nausea or vomiting was significantly more frequent in the TMZ + CAP treatment groups (arms B + D) than in the CAP treatment groups (arms A + C, P < 0.001) with no difference in grade 3 adverse events. There were no grade 4 or 5 adverse events. CONCLUSION: The addition of TMZ to CAP-based chemoradiotherapy tended to improve pCR rates, particularly in those with mMGMT LARC. MGMT status may warrant further investigation as a predictive biomarker for chemotherapeutic agents and radiotherapy.

Analgesic effects of a 5-HT3 receptor antagonist in an animal model of complex regional pain syndrome.

OBJECTIVE: Complex regional pain syndrome (CRPS) is caused by injuries from fracture after trauma and orthopaedic surgical procedures in the hind limbs. The symptoms of CRPS include warmth, pain, allodynia, and hyperalgesia. It is known that 5-hydroxytryptamine 3 (5-HT3) receptors contribute to hyperalgesia, but their role has not yet been fully elucidated. This study investigated the mechanism of pain relief when a 5-HT3 receptor antagonist was administered in a CRPS animal model. MATERIALS AND METHODS: To establish a CRPS animal model, 10-week-old Sprague-Dawley rats were used in the experiment. On the fourth week post tibial fracture surgery, we performed the von Frey test to measure mechanical allodynia. After performing behavioural tests, we collected blood and tissue samples after sacrificing the animals. Enzyme-linked immunosorbent assay and western blot were also performed. RESULTS: The experimental tibia fracture model-induced CRPS animals elicited increased 5-HT3 receptor expression, and the 5-HT transporter was decreased in the brain stem after 4 weeks of surgical intervention. Additionally, in CRPS-induced animals, both the concentration of substance P and the level of interleukin 6 were increased peripherally and centrally. Treatment with the 5-HT3 receptor antagonist, ramosetron, exerted an analgesic effect in the paw withdrawal test and was dependent on the attenuation of the 5-HT3 receptor population with inflammatory pain mediators. CONCLUSIONS: These data suggest that treatment with the 5-HT3 receptor antagonist, ramosetron, in experimental CRPS animal models alleviated pain-related behaviours and may be a new therapeutic option or potential therapeutic agent for patients with CRPS.

Short-term outcomes of a multicentre randomized clinical trial comparing laparoscopic pylorus-preserving gastrectomy with laparoscopic distal gastrectomy for gastric cancer (the KLASS-04 trial).

BACKGROUND: There remain concerns about the safety and functional benefit of laparoscopic pylorus-preserving gastrectomy (LPPG) compared with laparoscopic distal gastrectomy (LDG). This study evaluated short-term outcomes of a randomized clinical trial (RCT) comparing LPPG with LDG for gastric cancer. METHODS: The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial was an investigator-initiated, open-label, parallel-assigned, superiority, multicentre RCT in Korea. Patients with cT1N0M0 cancer located in the middle third of the stomach at least 5 cm from the pylorus were randomized to undergo LPPG or LDG. Participants, care givers and those assessing the outcomes were not blinded to group assignment. Outcomes were 30-day postoperative morbidity rate and death at 90 days. RESULTS: Some 256 patients from nine institutions were randomized (LPPG 129 patients, LDG 127 patients) between July 2015 and July 2017 and outcomes for 253 patients were analysed. Postoperative complications within 30 days were seen in 19.3 and 15.5 per cent in the LPPG and LDG groups respectively (P = 0·419). Postoperative pyloric stenosis was observed in nine (7.2 per cent) and two (1·5 per cent) patients in the LPPG and LDG groups (P = 0·026) respectively. In multivariable analysis higher BMI was a risk factor for postoperative complications (odds ratio 1·17, 95 per cent c.i. 1·04 to 1·32; P = 0·011). Death at 90 days was zero in both groups. CONCLUSION: Postoperative complications and mortality was comparable in patients undergoing LPPG and LDG. Registration number: NCT02595086 (http://www.clinicaltrials.gov).

Association between Depressive Symptoms and Risk of Sarcopenia in Taiwanese Older Adults.

OBJECTIVES: Symptoms of depression and high risk of sarcopenia are common among the older population; however, the associations between these remain unclear. Thus, the present study identified whether depressive symptoms are associated with older adults' sarcopenia risks. PARTICIPANTS: This nationally representative study in Taiwan investigated the older adult population ( ≥ 65 years) using a telephone survey conducted between 2019 and 2020. DESIGN: Self-reported data obtained included depressive symptoms (5-item from Center for Epidemiological Studies-Depression scale), sarcopenia risks (SARC-F questionnaire), and individual characteristics. The generalized additive models were used to examine the nonlinear associations between depressive symptoms and the risk of sarcopenia. RESULTS: A total of 1,068 older Taiwanese adults (72.15 ± 5.71 years; 52.7% women) participated in the survey. In the unadjusted model, the results showed a significant nonlinear association between high scores on the CES-D and sarcopenia scores (p < .001). Even after adjusting for covariates (sex, age, residential areas, education, marital status, working status, living status, smoking, drinking, and BMI), it still showed a significant non-linear association (p < .001). CONCLUSION: The results indicated that depressive symptoms were nonlinearly related to older adults' sarcopenia risks. Interventions or programs aiming to alleviate depression can be an effective strategy to prevent sarcopenia in the older adult population.

Cell-free culture supernatant of Lactobacillus curvatus Wikim38 inhibits RANKL-induced osteoclast differentiation and ameliorates bone loss in ovariectomized mice.

This study was conducted to investigate the inhibitory effects of the cell-free culture supernatant of Lactobacillus curvatus Wikim 38 (LC38-CS) on RANKL-induced osteoclast differentiation and bone loss in a mice model of ovariectomy-induced post-menopausal osteoporosis. LC38-CS inhibited the RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by LC38-CS treatment of RANKL-treated BMDMs. In addition, LC38-CS decreased the RANKL-induced activation of the TRAF6/NF-κB/MAPKs axis at the early stage and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. PRMT1 and ADMA levels, new biomarkers for osteoclastogenesis, were decreased by LC38-CS treatment. The administration of LC38-CS increased bone volume and bone mineral density in ovariectomized mice in µ-CT analysis. These findings suggest that LC38-CS inhibited RANKL-induced osteoclast differentiation by the downregulation of molecular mechanisms and exerted anti-osteoporotic effects.

A Nonlinear Association between Neighborhood Walkability and Risks of Sarcopenia in Older Adults.

OBJECTIVES: Neighborhood walkability has been found to be positively related to physical activity and negatively associated with risks of noncommunicable diseases. However, limited studies have examined its association with sarcopenia in older adults. Thus, this study aimed to examine the association between neighborhood walk score and risks of sarcopenia in a sample of older Taiwanese adults. DESIGN AND SETTING: This study was a cross-sectional investigation using telephone-based survey. PARTICIPANTS: A nationwide telephone-based survey targeting older adults (≥ 65 years) was conducted in Taiwan. MEASUREMENTS: Data on neighborhood walkability (determined by walk score of residential neighborhood), sarcopenia scores (measured by SARC-F), and personal characteristics were obtained. The relationships between walk score and risks of sarcopenia were examined using generalized additive models. RESULTS: A total of 1,056 older adults participated in the survey. In model 1 (sex and age) and model 2 (full-adjusted model), a nonlinear association between neighborhood walk score and risks of sarcopenia was observed. Results showed that risks of sarcopenia appear to be lower in neighborhoods with a 40-walk score (Car-Dependent; most errands require a car) and an 80-walk score (Very Walkable) and highest in the neighborhood with a 60-walk score (Somewhat Walkable). CONCLUSIONS: The study revealed a nonlinear relationship between neighborhood walkability and risks of sarcopenia in older adults in Asian context. Results provided information to urban designers and public health practitioners that more walkable neighborhood may not necessarily protect older adults from risks of sarcopenia.

Tunable high-temperature itinerant antiferromagnetism in a van der Waals magnet.

Discovery of two dimensional (2D) magnets, showing intrinsic ferromagnetic (FM) or antiferromagnetic (AFM) orders, has accelerated development of novel 2D spintronics, in which all the key components are made of van der Waals (vdW) materials and their heterostructures. High-performing and energy-efficient spin functionalities have been proposed, often relying on current-driven manipulation and detection of the spin states. In this regard, metallic vdW magnets are expected to have several advantages over the widely-studied insulating counterparts, but have not been much explored due to the lack of suitable materials. Here, we report tunable itinerant ferro- and antiferromagnetism in Co-doped Fe4GeTe2 utilizing the vdW interlayer coupling, extremely sensitive to the material composition. This leads to high TN antiferromagnetism of TN ~ 226 K in a bulk and ~210 K in 8 nm-thick nanoflakes, together with tunable magnetic anisotropy. The resulting spin configurations and orientations are sensitively controlled by doping, magnetic field, and thickness, which are effectively read out by electrical conduction. These findings manifest strong merits of metallic vdW magnets as an active component of vdW spintronic applications.

Investigation of the optimal medium and application strategy for foot-and-mouth disease vaccine antigen production.

AIMS: For the effective production of 146S particles, which determines foot-and-mouth disease (FMD) vaccine efficacy, we aimed to identify the optimal medium that is easy-to-use, productive and economically affordable for the large-scale production of FMD vaccine. METHODS AND RESULTS: Nine combinations of cell growth media and replacement media were tested for virus propagation. Apart from the replacement strategy, we tested a simple addition strategy involving the addition of 30% v/v of fresh medium to the total spent medium using the Cellvento BHK-200 (Vento). Unlike other tested media that produced poor yields of 146S particles when the spent media were not eliminated, Vento exhibited high productivity with the 30% addition strategy. CONCLUSIONS: Considering its lower price and media consumption compared to those of other media that require media replacement, the 30% addition strategy of Vento is highly effective. Furthermore, owing to its simple application strategy, it makes the scale-up process easy and helps in saving the time and labour involved in spent media removal. SIGNIFICANCE AND IMPACT OF THE STUDY: Through the first comparative assessment of commercial media for the 146S particle recovery, this study suggests the best practical medium for the industrial-scale production of FMD vaccines.

Computer-Aided Diagnostic System for Thyroid Nodules on Ultrasonography: Diagnostic Performance Based on the Thyroid Imaging Reporting and Data System Classification and Dichotomous Outcomes.

BACKGROUND AND PURPOSE: Artificial intelligence-based computer-aided diagnostic systems have been introduced for thyroid cancer diagnosis. Our aim was to compare the diagnostic performance of a commercially available computer-aided diagnostic system and radiologist-based assessment for the detection of thyroid cancer based on the Thyroid Imaging Reporting and Data Systems (TIRADS) and dichotomous outcomes. MATERIALS AND METHODS: In total, 372 consecutive patients with 454 thyroid nodules were enrolled. The computer-aided diagnostic system was set up to render a possible diagnosis in 2 formats, the Korean Society of Thyroid Radiology (K)-TIRADS and the American Thyroid Association (ATA)-TIRADS-classifications, and dichotomous outcomes (possibly benign or possibly malignant). RESULTS: The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the computer-aided diagnostic system for thyroid cancer were, respectively, 97.6%, 21.6%, 42.0%, 93.9%, and 49.6% for K-TIRADS; 94.6%, 29.6%, 43.9%, 90.4%, and 53.5% for ATA-TIRADS; and 81.4%, 81.9%, 72.3%, 88.3%, and 81.7% for dichotomous outcomes. The sensitivities of the computer-aided diagnostic system did not differ significantly from those of the radiologist (all P > .05); the specificities and accuracies were significantly lower than those of the radiologist (all P < .001). Unnecessary fine-needle aspiration rates were lower for the dichotomous outcome characterizations, particularly for those performed by the radiologist. The interobserver agreement for the description of K-TIRADS and ATA-TIRADS classifications was fair-to-moderate, but the dichotomous outcomes were in substantial agreement. CONCLUSIONS: The diagnostic performance of the computer-aided diagnostic system varies in terms of TIRADS classification and dichotomous outcomes and relative to radiologist-based assessments. Clinicians should know about the strengths and weaknesses associated with the diagnosis of thyroid cancer using computer-aided diagnostic systems.