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Introduction: Blood pressure is closely linked with immune function. This study examined the association between natural killer (NK) cell activity (NKA) and blood pressure and the development of hypertension according to NKA levels. Methods: This study enrolled 1543 adults who underwent NKA measurement and serial health check-ups at a medical center in Korea. NKA was estimated as the concentration of IFN-g in the incubated whole blood containing a patented stimulatory cytokine. The participants were categorized into quartiles according to their NKA levels. Participants without hypertension were followed up, and the development of hypertension was compared according to the quartiles. Results: The prevalence of hypertension was not different among the NKA quartiles, whereas blood pressures significantly decreased, followed by an increment of quartiles (systolic blood pressure of 119.0 in Q1 and 117.0 in Q4, P-trend = 0.018). Over a mean follow-up period of 2.13 years, hypertension developed in 156 of 1170 individuals without baseline hypertension. The hazard ratio of Q4 compared with Q1 was 0.625 (95% CI: 0.397-0.983; p = 0.042). Conclusion: In conclusion, our findings indicate a correlation between lower NKA and higher blood pressure and the development of incident hypertension. This may suggest a potential protective role of NK cells against endothelial dysfunction. Further research is necessary to elucidate the specific relationship between immune functions and endothelial function. [ABSTRACT FROM AUTHOR]

Background: We aimed to elucidate the mechanism of change in mitochondrial fusion- and fission-related mediators for maintaining cell function through the effects of acupuncture treatment and apply findings to a liver disease model. We focused on the optic atrophy-1 (OPA1) and fission protein 1 (Fis1) genes of rat liver cells. Methods: Sprague Dawley rats were divided into a control group (no treatment) and LR2, LR3, LR4 and LR8 groups (acupuncture treatment to those points). Acupuncture was performed on each point for 10 minutes once daily for 4 days. Changes in the mRNA expression of Peroxisome proliferator-activated receptor-gamma coactivator 1-a (PGC-1a) and Fis1 were observed via quantitative real-time polymerase chain reaction (qRT-PCR); changes in OPA1, mitofusin-2 (MFN2), mitofusin-1 (MFN1), dynamin-related protein 1 (DRP1) and adenosine monophosphate-activated protein kinase (AMPK) proteins were observed through western blotting and endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) expressions were observed through immunohistochemistry. Result: OPA1 decreased in the LR3 and LR8 groups and Fis1 increased in the LR2 and LR4 groups. AMPK and PGC-1a decreased significantly in all acupuncture groups. eNOS and nNOS expression reduced in all acupuncture groups. Therefore, acupuncture can regulate mitochondrial fusion/fission by influencing the following mediators: AMPK, PGC-1a, OPA1, Fis1, eNOS and nNOS. [ABSTRACT FROM AUTHOR]

A continuous selection of polynomial functions is a continuous function whose domain can be partitioned into finitely many pieces on which the function coincides with a polynomial. Given a set of finitely many polynomials, we show that there are only finitely many continuous selections of it and each one is semi-algebraic. Then, we establish some generic properties regarding the critical points, defined by the Clarke subdifferential, of these continuous selections. In particular, given a set of finitely many polynomials with generic coefficients, we show that the critical points of all continuous selections of it are finite and the critical values are all different, and we also derive the coercivity of those continuous selections which are bounded from below. We point out that some existing results about Łojasiewicz’s inequality and error bounds for the maximum function of some finitely many polynomials can be extended to all the continuous selections of them. [ABSTRACT FROM AUTHOR]

Background: The design of clinical trials in rare diseases is often complicated by a lack of real-world translational knowledge. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by skeletal malformations and progressive heterotopic ossification (HO). Palovarotene is a selective retinoic acid receptor gamma agonist. Here, we describe the methodology of three studies in the palovarotene clinical development program in FOP and discuss insights that could inform future research, including endpoint suitability and the impact of trial design. Methods: PVO-1A-001 (NCT02322255) was a prospective, protocol-specified, longitudinal FOP natural history study (NHS). PVO-1A-201 (NCT02190747) was a randomized, double-blind, placebo-controlled phase II trial; PVO-1A-202 (NCT02279095) was its open-label extension. Trial designs, including treatment regimens and imaging assessments, were refined between PVO-1A-201 and PVO-‍1A-202, and within PVO-1A-202, based on emerging data as the studies progressed. Palovarotene doses were administered using a flare-up treatment regimen (higher dose for 2/4 weeks, followed by lower dose for 4/≥8 weeks; from flare-up onset), with or without accompanying chronic (daily) treatment. Flare-up and disease progression outcomes were assessed, including incidence and volume of new HO during flare-ups and/or annually, as well as other clinical, patient-reported, and exploratory outcomes. Safety was monitored throughout all studies. Results: Overall, 114 and 58 individuals with FOP were enrolled in the NHS and phase II trials, respectively. Results of the NHS and PVO-1A-201 were published in 2022; complete results of PVO-1A-202 will be publicly available in due course. Together the studies yielded important information on endpoint suitability, including that low-dose whole-body computed tomography was the optimum imaging modality for assessing HO progression annually and that long study durations are needed to detect substantial changes in functional and patient-reported outcomes. Conclusions: A flexible clinical development program is necessary for underexplored rare diseases to overcome the many challenges faced. Here, the NHS provided a longitudinal evaluation of FOP progression and interventional trials were based on emerging data. The studies described informed the design and endpoints implemented in the phase III MOVE trial (NCT03312634) and provide a foundation for future clinical trial development. Trial registration: NCT02322255 (registered 23/12/2014); NCT02190747 (registered 15/07/2014); NCT02279095 (registered 30/10/2014). [ABSTRACT FROM AUTHOR]

In this study, we have developed an amplifier waveguide module suitable for broadband communication in the sub-THz band. To achieve a waveguide module with excellent gain flatness characteristics, the effects of errors during the packaging procedures of the waveguide module and the space occupied by the bondwire were analyzed through an electromagnetic simulation. Furthermore, a photonics-based sub-THz wireless link with a carrier frequency of 288 GHz was established using a packaged amplifier module. The amplifier module was placed at the output of the sub-THz transmitter based on a uni-traveling-carrier photodiode and at the input of the sub-THz receiver. The maximum gain and 3 dB bandwidth of the amplifier module are 17.3 dB and 39 GHz, respectively. With this setup, we successfully transmitted a 100-Gbps 16-QAM modulated signal, employing a carrier frequency of 288 GHz, across a wireless distance of 100 m. [ABSTRACT FROM AUTHOR]

Background and Objectives: Palovarotene is under development for the treatment of fibrodysplasia ossificans progressiva (FOP). The objectives of this study were to evaluate palovarotene pharmacokinetics under fed versus fasted conditions and its induction potential towards cytochrome P450 3A4 (CYP3A4) substrate, midazolam. Methods: In this phase I, open-label trial (NCT04829773), palovarotene pharmacokinetics were characterized after repeated once-daily dosing. In one cohort, healthy participants received three doses of palovarotene 20 mg on Days 1, 6, and 11, as whole capsules under fasted or fed conditions, or sprinkled on food under fed conditions. In another cohort, individuals received midazolam 2 mg on Days 1 and 15 and a daily dose of palovarotene 20 mg on Days 2–15. Palovarotene and midazolam pharmacokinetics, including area under the concentration-time curve from time zero to infinity (AUC(0–∞)) and maximum observed plasma drug concentration (Cmax), were assessed. Adverse events (AEs) were recorded. Results: Overall, 23 participants completed each part. Palovarotene Cmax and AUC(0–∞) increased by 16.5% and 39.7% under fed versus fasted conditions. Pharmacokinetics were comparable between the whole capsule and sprinkled on food, under fed conditions. Midazolam AUC(0–∞) and Cmax decreased by 13.3% and 9.7% upon palovarotene co-administration over 14 days, less than that required to be considered a weak CYP3A4 inducer. Plasma palovarotene exposures were comparable after single and multiple doses. No serious AEs were reported. Conclusions: These data support palovarotene administration after a meal, as a whole capsule or sprinkled on food. Palovarotene at 20 mg/day is a not a clinical inducer of CYP3A4. These results provide insights into palovarotene pharmacokinetics, aiding optimization of administration for patients with FOP. Clinical Trials Registration Number: NCT04829773. Plain Language Summary: Fibrodysplasia ossificans progressiva, also known as FOP, is a very rare genetic condition where bone forms in places it is not usually found, such as in the muscles, tendons, and ligaments. Retinoids are molecules that the body produces from vitamin A to aid normal bone development. Palovarotene is a therapeutic retinoid that has been developed for the treatment of FOP. This article describes a clinical trial where people without FOP received oral palovarotene to determine how it is absorbed and broken down (metabolized) by the body when taken after a meal or after fasting (a period of not eating) as a whole capsule or when sprinkled on food. The trial also examined how palovarotene might interact with other treatments that are broken down by the body in the same way as palovarotene. The trial found that the amount of palovarotene that circulates in the blood increased more when taken after a meal compared with after fasting. Palovarotene was metabolized by the body in a similar way when taken as a whole capsule or when sprinkled on food. This finding is important as some people with FOP have difficulty swallowing. At a 20 mg dose, palovarotene was unlikely to interact with other treatments that are metabolized in the same way. No serious side effects were reported. These results show that palovarotene should be taken after a meal, either as a whole capsule or sprinkled on food. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin is a neurotoxic substance with a wide range of uses, from the treatment of musculoskeletal spasms to anti-aging regimens by improving wrinkles. Split-face studies in which drugs are injected in the right and left sides of the faces have been actively conducted in botulinum toxin studies. In this study, we aimed to investigate the reliability of a split-face study for determining the effectiveness of botulinum toxin based on eyebrow height and movement, and electromyography results. Methods: Thirty-one women aged 35 to 55 years were included in the study. Eyebrow height was measured as the distance from the eyebrows to the upper eyelid margin on the primary gaze, and eyebrow movement was measured as the distance when the forehead was wrinkled for 5 seconds. A noninvasive method was used for electromyography of the frontalis muscles. Results: No statistically significant differences in right and left eyebrow heights and movements, and electromyography findings (p= 0.256, p= 1.000, and p= 0.978, respectively) were found. Pearson correlation analysis showed that electromyography muscle activity is positively associated with eyebrow movement, respectively (p< 0.001). Conclusion: We advocate the reliability of split-face study and the usefulness of electromyography of frontalis muscle in forehead rejuvenation research. [ABSTRACT FROM AUTHOR]

Purpose: Healthy aging is an important concern in an aging society. Although the causal relationship between hypogonadism and erectile dysfunction in elderly men remains unclear, many physicians have achieved positive results after implementing exogenous testosterone supplementation therapy in patients with normal or slightly low blood testosterone. The purpose of this study was to conduct a systematic review and meta-analysis on whether testosterone replacement therapy (TRT) could improve sexual function in the elderly, as reported recently. Materials and Methods: As a comprehensive literature search was performed to find articles published in PubMed, Embase, and Cochrane databases by January 2022. The search used keywords of ‘aged’, ‘male’, ‘sexual behavior’, and ‘testosterone’. Randomized controlled trials (RCTs) were finally selected. As the main effect variable, results of a questionnaire on sexual function were analyzed and the effects of TRT were compared to those of placebo control. Results: Five RCT studies were included in this meta-analysis. The overall improvement by mean difference of sexual function for testosterone supplementation was 0.082 (95% CI: -0.049 to 0.213). In subgroup analysis, only intramuscular injection of 1,000 mg testosterone significantly improved sexual function of the elderly (0.229, 95% CI: 0.112 to 0.347). There was no significant difference in sexual function according to testosterone dose in meta-ANOVA (p=0.957). The difference was not statistically significant either in the meta-regression test (p=0.310). Egger’s regression coefficient test did not indicate a publication bias (p=0.132). Conclusions: Although our overall effect size (that is, sexual function effect of TRT) did not show a significant improvement, the direction of improvement in erection and motivation was clearly shown. The injection formulation resulted in a significant sexual function improvement. Since only a few RCTs were included in the analysis, more well-designed prospective studies are needed to have a definite conclusion. [ABSTRACT FROM AUTHOR]

Background/Aim: Programmed death ligand-1 (PD-L1) expression is known to be a predictive biomarker for response to immunotherapy in non-small cell lung cancer (NSCLC). However, PD-L1 is not always a reliable predictive biomarker. In the present study, we aimed to compare responses to immunotherapy according to smoking status in NSCLC patients receiving immunotherapy in second line or further line treatment. Patients and Methods: The lung cancer registry database of the Catholic Medical Center, Seoul, Republic of Korea was used. Patients were eligible for this study if they were diagnosed with histologically confirmed NSCLC and received immune checkpoint inhibitors (ICIs) as second-line or further line therapy from January 2017 to December 2021. Results: Overall, 220 patients with NSCLC treated with ICIs were enrolled. There were 40 never smokers, 73 former smokers, and 107 current smokers. In multivariate analysis, smoking status, pathologic type, and PD-L1 expression were significant factors affecting PFS. Sex, ECOG performance status, pathologic type, and PD-L1 expression were significant factors affecting OS. Conclusion: Smoking status at diagnosis of lung cancer could be a predictive biomarker for response to ICIs in patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to perform a comparative analysis of metabolite levels in serum and milk obtained from cows fed on different concentrate to forage feed ratios. Methods: Eight lactating Holstein cows were divided into two groups: a high forage ratio diet (HF; 80% Italian ryegrass and 20% concentrate of daily intake of dry matter) group and a high concentrate diet (HC; 20% Italian ryegrass and 80% concentrate) group. Blood was collected from the jugular vein, and milk was sampled using a milking machine. Metabolite levels in serum and milk were estimated using proton nuclear magnetic resonance and subjected to qualitative and quantitative analyses performed using Chenomx 8.4. For statistical analysis, Student's t-test and multivariate analysis were performed using Metaboanalyst 4.0. Results: In the principal component analysis, a clear distinction between the two groups regarding milk metabolites while serum metabolites were shown in similar. In serum, 95 metabolites were identified, and 13 metabolites (include leucine, lactulose, glucose, betaine, etc.) showed significant differences between the two groups. In milk, 122 metabolites were identified, and 20 metabolites (include urea, carnitine, acetate, butyrate, arabinitol, etc.) showed significant differences. Conclusion: Our results show that different concentrate to forage feed ratios impact the metabolite levels in the serum and milk of lactating Holstein cows. A higher number of metabolites in milk, including those associated with milk fat synthesis and the presence of Escherichia coli in the rumen, differed between the two groups compared to that in the serum. The results of this study provide a useful insight into the metabolites associated with different concentrate to forge feed ratios in cows and may aid in the search for potential biomarkers for subacute ruminal acidosis. [ABSTRACT FROM AUTHOR]

Worldwide, cardiovascular diseases and associated morbidity have been on a constant rise for the past few years. However, heart transplantation remains a distant option for many owing to demand-supply issues. A completely bio-engineered heart is still a far vision for the hoping patients. The evolving area of cardiac tissue engineering provides a chance to fabricate bioactive scaffolds which would aid in functioning and supporting the cardiac tissues by mimicking the mechanical, chemical, and biological properties of the native tissue. Numerous fibrous scaffolds have been studied and are currently under study in cardiac tissue engineering. This review overviews the latest developments of the electrospun fibrous scaffold decorated with growth factors/cytokines, bioactive nanoparticles, and conductive fibers in cardiac tissue engineering that will help in the beneficial functioning of the cardiac system. [ABSTRACT FROM AUTHOR]

Background & Aims: Fusobacterium nucleatum (FN) plays a pivotal role in the development and progression of colorectal cancer by modulating antitumor immune responses. However, the impact of FN on immune regulation in the tumor microenvironment has not been fully elucidated. Methods: The abundance of FN was measured in 99 stage III CRC tumor tissues using quantitative polymerase chain reaction. Gene expression profiles were assessed and annotated using consensus molecular subtypes (CMS), Gene Ontology (GO) analysis, and deconvolution of individual immune cell types in the context of FN abundance. Immune profiling for tumor infiltrating T cells isolated from human tumor tissues was analyzed using flow cytometry. Ex vivo tumor-infiltrating T cells were stimulated in the presence or absence of FN to determine the direct effects of FN on immune cell phenotypes. Results: Gene expression profiles, CMS composition, abundance of immune cell subtypes, and survival outcomes differed depending on FN infection. We found that FN infection was associated with poorer disease-free survival and overall survival in stage III CRC patients. FN infection was associated with T cell depletion and enrichment of exhausted CD8+ and FoxP3+ regulatory T cells in the tumor microenvironment. The presence of FN in tumors was correlated with a suppressive tumor microenvironment in a T cell-dependent manner. Conclusion: FN enhanced the suppressive immune microenvironment with high depletion of CD8+ T cells and enrichment of FoxP3+ regulatory T cells in human colorectal cancer cases. Our findings suggest a potential association for FN in adaptive immunity, with biological and prognostic implications. [ABSTRACT FROM AUTHOR]

Background and Objective: Palovarotene is an oral, selective retinoic acid receptor gamma agonist under investigation for fibrodysplasia ossificans progressiva (FOP). Palovarotene is primarily metabolized by cytochrome P450 (CYP) 3A4. Differences in CYP-mediated metabolism of CYP substrates have been observed between Japanese and non-Japanese individuals. This phase I trial (NCT04829786) compared the pharmacokinetic profile of palovarotene in healthy Japanese and non-Japanese participants and evaluated the safety of single doses. Methods: Healthy Japanese and non-Japanese participants were matched individually (1:1) and randomized to receive a single oral dose of palovarotene 5 or 10 mg, followed by the alternate dose after a 5-day washout period. Maximum plasma drug concentration (Cmax) and area under the plasma concentration–time curve (AUC) were assessed. Estimates of the geometric mean difference between dose and Japanese and non-Japanese groups were calculated for natural log-transformed Cmax and AUC parameters. Adverse events (AEs), serious AEs, and treatment-emergent AEs were recorded. Results: Eight pairs of matched non-Japanese and Japanese individuals and two unmatched Japanese individuals participated. Mean plasma concentration–time profiles were similar between the two cohorts at both dose levels, demonstrating that palovarotene absorption and elimination are similar irrespective of dose level. The pharmacokinetic parameters of palovarotene were similar between groups at both dose levels. Cmax and AUC values were dose-proportional between doses in each group. Palovarotene was well tolerated; there were no deaths or AEs leading to treatment discontinuation. Conclusions: Japanese and non-Japanese groups had similar pharmacokinetic profiles, indicating that palovarotene dose adjustments are not necessary for Japanese patients with FOP. [ABSTRACT FROM AUTHOR]

Objective: In this study, metabolites that changed in the rumen fluid, urine and feces of dairy cows fed different feed ratios were investigated. Methods: Eight Holstein cows were used in this study. Rumen fluid, urine, and feces were collected from the normal concentrate diet (NCD) (Italian ryegrass 80%: concentrate 20% in the total feed) and high concentrate diet (HCD) groups (20%: 80%) of dairy cows. Metabolite analysis was performed using proton nuclear magnetic resonance (NMR) identification, and statistical analysis was performed using Chenomx NMR software 8.4 and Metaboanalyst 4.0. Results: The two groups of rumen fluid and urine samples were separated, and samples from the same group were aggregated together. On the other hand, the feces samples were not separated and showed similar tendencies between the two groups. In total, 160, 177, and 188 metabolites were identified in the rumen fluid, urine, and feces, respectively. The differential metabolites with low and high concentrations were 15 and 49, 14 and 16, and 2 and 2 in the rumen fluid, urine, and feces samples, in the NCD group. Conclusion: As HCD is related to rumen microbial changes, research on different metabolites such as glucuronate, acetylsalicylate, histidine, and O-Acetylcarnitine, which are related to bacterial degradation and metabolism, will need to be carried out in future studies along with microbial analysis. In urine, the identified metabolites, such as gallate, syringate, and vanillate can provide insight into microbial, metabolic, and feed parameters that cause changes depending on the feed rate. Additionally, it is thought that they can be used as potential biomarkers for further research on subacute ruminal acidosis. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles secreted by tumor cells contain doublestranded DNA called extracellular vesicle DNA (evDNA). EvDNA is genomic DNA that reflects cancer driver mutations. However, the significance of evDNA analysis in the diagnosis and surveillance of colon cancer remains unclear. This study aimed to investigate the clinical utility of extracellular vesicles and evDNA isolated from the plasma of colon cancer patients harboring KRAS G12D and G13D mutations. Methods: Cell-free DNA (cfDNA) and evDNA were collected from the plasma of 30 patients with colon cancer. KRAS mutation status (G12D and G13D) was detected using a droplet digital polymerase chain reaction assay (ddPCR). Sensitivity and specificity were evaluated in patients with wild-type KRAS tumors. Mutation status was correlated with carcinoembryonic antigen (CEA) levels and overall survival (OS). Results: Thirty cfDNA and evDNA pairs showed a KRAS fractional abundance (FA) ranging from 0 to 45.26% and 0 to 83.81%, respectively. When compared with eight wild-type KRAS samples, cfDNA exhibited 70% sensitivity and 100% specificity, whereas evDNA achieved 76.67% sensitivity and 100% specificity. The concentration of evDNA was significantly lower than that of cfDNA, but it obtained a higher FA than cfDNA, while showing a positive correlation with CEA. Conclusions: Our findings demonstrate the feasibility of evDNA as a complementary tool to aid current methods of patient evaluation in the diagnosis and surveillance of colon cancer. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the impact of plate type on the clinical and radiological outcomes of ulnar shortening osteotomy (USO) by comparing conventional and ulnar osteotomy plates. The effect of interfragmentary screw fixation (ISF) during USO was also assessed. Methods: Seventy-eight patients were divided into three groups according to the type of plate: 3.5-mm dynamic compression plate (DCP), 3.5-mm limited contact DCP, and 2.7-mm locking compression plate ulna osteotomy system (all from Depuy-Synthes). The patients were also divided into two groups according to whether ISF was performed. Clinical and radiological outcomes, including time to bone union, presence of delayed union, and refracture after hardware removal, were analyzed. Other factors that might affect bone union, such as smoking and underlying diseases, were also evaluated. Results: No significant differences were found in clinical and radiological outcomes according to the type of plate. Eight of 51 patients (15.7%) in the without-ISF group showed delayed bone union. Forty-three patients in the without-ISF group underwent hardware removal, and refracture due to low-energy trauma after hardware removal was observed in five of those 43 patients (11.6%). Bone union time was significantly shorter in the with-ISF group (7.6±2.7 weeks vs. 9.8±6.6 weeks). Diabetes mellitus and ISF were associated with the delayed bone union. Conclusion: The plate type had no influence on the clinical and radiological outcomes of USO in patients with idiopathic ulnar impaction syndrome. However, ISF during USO has several advantages, such as early bony union and prevention of refracture after hardware removal. [ABSTRACT FROM AUTHOR]

Nitisinone (NTBC) was recently approved to treat alkaptonuria (AKU), but there is no information on its impact on oxidative stress and inflammation, which are observed in AKU. Therefore, serum samples collected during the clinical studies SONIA1 (40 AKU patients) and SONIA2 (138 AKU patients) were tested for Serum Amyloid A (SAA), CRP and IL-8 by ELISA; Advanced Oxidation Protein Products (AOPP) by spectrophotometry; and protein carbonyls by Western blot. Our results show that NTBC had no significant effects on the tested markers except for a slight but statistically significant effect for NTBC, but not for the combination of time and NTBC, on SAA levels in SONIA2 patients. Notably, the majority of SONIA2 patients presented with SAA > 10 mg/L, and 30 patients in the control group (43.5%) and 40 patients (58.0%) in the NTBC-treated group showed persistently elevated SAA > 10 mg/L at each visit during SONIA2. Higher serum SAA correlated with lower quality of life and higher morbidity. Despite no quantitative differences in AOPP, the preliminary analysis of protein carbonyls highlighted patterns that deserve further investigation. Overall, our results suggest that NTBC cannot control the sub-clinical inflammation due to increased SAA observed in AKU, which is also a risk factor for developing secondary amyloidosis. [ABSTRACT FROM AUTHOR]

Background: Although more people are experiencing cybersickness due to the popularization of virtual reality (VR), no official standard for the cause and reduction of cybersickness exists to date. One of the main reasons is that an objective method to assess cybersickness has not been established. To resolve this, research on evaluating cybersickness with physiological responses that can be measured in real time is required. Since research on deriving physiological responses that can assess cybersickness is at an early stage, further studies examining various physiological responses are needed. Objective: This study analyzed the effects of cybersickness caused by head-mounted display--based VR on physiological responses. Methods: We developed content that provided users with a first-person view of an aircraft that moved (with translation and combined rotation) over a city via a predetermined trajectory. In the experiment, cybersickness and the physiological responses of participants were measured. Cybersickness was assessed by the Simulator Sickness Questionnaire (SSQ). The measured physiological responses were heart rate, blood pressure, body temperature, and cortisol level. Results: Our measurement confirmed that all SSQ scores increased significantly (all Ps<.05) when participants experienced cybersickness. Heart rate and cortisol level increased significantly (P=.01 and P=.001, respectively). Body temperature also increased, but there was no statistically significant difference (P=.02). Systolic blood pressure and diastolic blood pressure decreased significantly (P=.001). Conclusions: Based on the results of our analysis, the following conclusions were drawn: (1) cybersickness causes significant disorientation, and research on this topic should focus on factors that affect disorientation; and (2) the physiological responses that are suitable for measuring cybersickness are heart rate and cortisol level. [ABSTRACT FROM AUTHOR]

The aluminum composite with dispersed high entropy alloy were developed by stir casting involving the powder-in-tube method. First, Al0.5CoCrCuFeNi high entropy alloy (HEA) powder was made by mechanical alloying, and the powder was extruded in a tube-type aluminum container to form HEA precursor. The extruded HEA precursor was then dispersed in the aluminum matrix via stir casting. As a result, Fe-Cr-Ni based high-entropy phases was uniformly formed in the aluminum matrix, revealing ~158, 166, 235% enhancement of tensile strength by incorporating 1, 3, and 5 wt% HEA particles, respectively. [ABSTRACT FROM AUTHOR]

Background: Although emerging evidence suggests that periodontitis might increase the risk of cancer, comorbidity and lifestyle behaviors, such as smoking and body mass index (BMI), may have confounded this reported association. This study aimed to investigate whether chronic periodontitis is associated with cancer risk using a large, nationwide database. Methods: We conducted a population-based, retrospective cohort study using data from the Korean National Health Insurance Cohort Database obtained between January 2003 and December 2015. We included 713,201 individuals without a history of cancer who were followed up to 10 years. Confounding factors included demographic factors (age, sex, income, and residential area), lifestyle behaviors (smoking history and BMI), and comorbidities, such as hypertension, diabetes, heart failure, and pulmonary disease, using the Charlson Comorbidity Index. Multivariable Cox regression analysis was applied to estimate the adjusted hazard ratio (aHR) for cancer risk. Results: Of the 713,201 participants, 53,075 had periodontitis and were placed in the periodontitis group; the remaining 660,126 individuals were included as the control group. Overall, the cumulative incidence of cancer in the periodontitis group was 2.2 times higher than that in the control group. The periodontitis group had an increased risk of total cancer compared to the control group after adjusting for age, sex, comorbidities, BMI, and smoking history (aHR, 1.129; 95% confidence interval [CI], 1.089-1.171; P<0.0001). When examining specific cancer types, significant associations were also observed between periodontitis and stomach cancer (aHR, 1.136; 95% CI, 1.042-1.239; P=0.0037), colon cancer (aHR, 1.129; 95% CI, 1.029-1.239; P=0.0105), lung cancer (aHR, 1.127; 95% CI, 1.008-1.260; P=0.0353), bladder cancer (aHR, 1.307; 95% CI, 1.071-1.595; P=0.0085), thyroid cancer (aHR, 1.191; 95% CI, 1.085-1.308; P=0.0002), and leukemia (aHR, 1.394; 95% CI, 1.039-1.872; P=0.0270). There was no significant association between the development of secondary malignancy and periodontitis in cancer survivors who were alive 5 years after they were diagnosed with the primary malignancy. Conclusions: Periodontal disease, including periodontitis, was associated with increased risk of cancer, which persisted after controlling for confounding factors. Further prospective research is warranted to establish a causal relationship. [ABSTRACT FROM AUTHOR]

Acupuncture therapy is an essential part of traditional Chinese medicine that is being recognized by an increasing number of countries due to its convenience, effectiveness, and low risk of adverse reactions. The microenvironment is important in the occurrence, development, treatment, and rehabilitation of diseases, and has recently become a focus of research in the field of various diseases. Acupuncture's therapeutic effect on the human body begins in the microenvironment (acupoints) and ends in the microenvironment (lesions). Many reports on the mechanism of acupuncture and moxibustion are written with the impact of acupuncture on the microenvironment of different systems or parts in mind. Several diseases that have been widely reported in recent years, such as osteoarthritis, spinal cord injury, and tumors, have been chosen as examples. [ABSTRACT FROM AUTHOR]

Background: Recently, technology that provides virtual reality (VR) content based on streaming services has been rapidly developed. However, there have been few studies to reduce VR sickness that occurs while the user watches VR content while wearing a head-mounted display (HMD) in real time. Objective: Based on this background, we propose a new approach to measure and reduce VR sickness that occurs while the user watches VR content while wearing an HMD in real time. Methods: The proposed approach is to apply VR sickness reduction methods in accordance with the user's real-time VR sickness level. Three methods that are known to be effective in reducing VR sickness and a single type of VR content were used to examine the effectiveness of the proposed approach, which was confirmed by the experimental results. Results: Our results show that VR sickness significantly decreased when a new approach was applied to VR content (in all cases, P<.05). Conclusions: From our results, it was confirmed that VR sickness could be measured without wearing additional equipment, and its reduction method could be applied in real time in accordance with the user's condition by the proposed approach in this paper. [ABSTRACT FROM AUTHOR]

Background: Serology testing is useful to determine the past infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We evaluated the comparative performance of a newly developed neutralizing antibody test (R-FIND SARS-CoV-2 Neutralizing Antibody ELISA, SG Medical, Seoul, Korea) and a rapid fluorescence immunoassay (FRENDâ„¢ COVID-19 SP, NanoEntek, Hwaseong, Korea) for the detection of SARS-CoV-2 spike protein antibody. They were compared with cPassâ„¢ SARS-CoV-2 Neutralization Antibody Detection Kit (Genscript Biotech, Piscataway, NJ, USA) and ADVIA Centaur SARS-CoV-2 Total (COV2T) (Siemens Healthineers, Erlangen, Germany). Forty COVID-19 samples and 80 negative samples were collected after nucleic acid tests. Results: The positive percent agreement (%) of the kit in samples from 6 - 7 days, 8 - 14 days, and 15 - 45 days after symptom onset were as follows: R-FIND (83.3, 76.9, 95.2), cPass (83.3, 69.2, 90.5), FREND (66.6, 84.6, 100), and COV2T (66.6, 69.2, 76.2). The negative percent agreement (%) was 100, 97.5, 92.5, and 100 for R-FIND, cPass, FREND, and COV2T. The total agreement rate between the neutralizing antibody kits (R-FIND and cPass) was 96.7%. FREND showed high agreement with two neutralizing antibody kits (96.7% for R-FIND and 93.3% for cPass). Conclusions: R-FIND Neutralizing Antibody and FREND COVID-19 SP showed comparable detecting ability to commercial tests. [ABSTRACT FROM AUTHOR]

Purpose Preclinical data indicate that response to radiotherapy (RT) depends on DNA damage repair. In this study, we investigated the role of mutations in genes related to DNA damage repair in treatment outcome after RT. Materials and Methods Patients with solid tumor who participated in next generation sequencing panel screening using biopsied tumor tissue between October 2013 and February 2019 were reviewed and 97 patients that received RT were included in this study. Best response to RT and the cumulative local recurrence rate (LRR) were compared according to absence or presence of missense, nonsense, and frameshift mutations in ATM and/or BRCA1/2. Results Of the 97 patients, five patients harbored mutation only in ATM, 22 in only BRCA1/2, and six in both ATM and BRCA1/2 (ATMmtBRCAmt). Propensity score matching was performed to select the control group without mutations (ATMwtBRCAwt, n=33). In total, 90 RT-treated target lesions were evaluated in 66 patients. Highest objective response rate of 80% was observed in ATMmtBRCAmt lesions (p=0.007), which was mostly durable. Furthermore, the cumulative 1-year LRR was the lowest in ATMmtBRCAmt lesions and the highest in ATMwtBRCAwt lesions (0% vs. 47.9%, p=0.008). RT-associated toxicities were observed in 10 treatments with no significant difference among the subgroups (p=0.680). Conclusion Tumors with ATM and BRCA1/2 mutations exhibited superior tumor response and local control after RT compared to tumors without these mutations. The results are hypothesis generating and suggest the need for integrating the tumor mutation profile of DNA repair genes during treatment planning. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea's public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion. [ABSTRACT FROM AUTHOR]

Targeted molecular imaging with PET uses chemical ligands that are peptides specifically targeting a receptor of interest. Prostate-specific membrane antigen (PSMA) is substantially upregulated in prostate cancer but is also expressed in the neovascular tissue of several malignancies, including renal cell carcinoma (RCC). Radiolabeled peptide targets for PSMA may be helpful in detecting metastatic RCC lesions. We present a case of incidental detection of RCC metastatic disease with PSMA-targeted PET, and we explore potential use for deliberate evaluation of RCC with PSMA-targeted tracers. [ABSTRACT FROM AUTHOR]

The Covid-19 pandemic has accelerated Korea’s progression towards an ‘untact’, or contactless, economy. Working from home is now a culture for many, and digital transactions and services are becoming a necessity for businesses and consumers. With many of today’s social and economic activities taking place online, digital markets in Korea have grown exponentially in recent years and are expected to fundamentally change both personal and professional lives. Amid this rapidly evolving digital landscape, enforcement authorities in Korea – including its competition law authority, the Korea Fair Trade Commission (KFTC) and information communications technology sector regulator, the Korea Communications Commission (KCC) – are proactively addressing new competition and consumer protection issues arising from the digital economy, leading to an increasing number of multilateral regulatory probes. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to conduct metabolic profiling of dairy cattle serum and urine using proton nuclear magnetic resonance (1H-NMR) spectroscopy and to compare the results obtained with those of other dairy cattle herds worldwide so as to provide a basic dataset to facilitate research on metabolites in serum and urine. Methods: Six dairy cattle were used in this study; all animals were fed the same diet, which was composed of total mixed ration; the fed amounts were based on voluntary intake. Blood from the jugular neck vein of each steer was collected at the same time using a separate serum tube. Urine samples were collected by hand sweeping the perineum. The metabolites were determined by 1H-NMR spectroscopy, and the obtained data were statistically analyzed by performing principal component analysis, partial least squares-discriminant analysis, variable importance in projection scores, and metabolic pathway data using Metaboanalyst 4.0. Results: The total number of metabolites in the serum and urine was measured to be 115 and 193, respectively, of which 47 and 81, respectively were quantified. Lactate (classified as an organic acid) and urea (classified as an aliphatic acylic compound) exhibited the highest concentrations in serum and urine, respectively. Some metabolites that have been associated with diseases such as ketosis, bovine respiratory disease, and metritis, and metabolites associated with heat stress were also found in the serum and urine samples. Conclusion: The metabolites measured in the serum and urine could potentially be used to detect diseases and heat stress in dairy cattle. The results could also be useful for metabolomic research on the serum and urine of ruminants in Korea. [ABSTRACT FROM AUTHOR]

Background/Aim: Little is known about the prognostic role of the Glasgow prognostic score (GPS) in nonsmall cell lung cancer (NSCLC) patients treated with immunotherapy after platinum-based cytotoxic chemotherapy. Patients and Methods: This study used a lung cancer cohort of the Catholic Medical Center of Korea between January 2018 and September 2020. Results: A total of 78 patients with NSCLC treated with immunotherapy as second or further-line therapy were included. Higher GPS values were significant predictors of shorter immune-related progression-free survival (irPFS) and overall survival (OS). The hazard ratios for irPFS were 0.249 for programmed death-ligand 1 (PD-L1) expression ≥50% and 9.73 for a GPS of 2. Older age, lower PD-L1 expression and higher GPS values were independently associated with shorter OS. Conclusion: Higher GPS values were identified as a poor prognostic factor for OS and irPFS in NSCLC patients who received immunotherapy as second or further-line therapy. [ABSTRACT FROM AUTHOR]

This paper focuses on the study of optimality conditions (both necessary and sufficient) for a weakly quasi e-Pareto solution to a multiobjective optimization problem by using a minimax programming approach. To establish necessary conditions for approximate solutions of minimax programming problems under a suitable constraint qualification, we use some advanced tools of variational analysis and generalized differentiation. Sufficient conditions for such solutions to the considered problem are also provided by using generalized convex functions defined in terms of the limiting subdifferential for locally Lipschitz functions. In addition, some duality results for minimax programming problems are also provided. [ABSTRACT FROM AUTHOR]

In this paper, employing some advanced tools of variational analysis and generalized differentiation, we establish necessary conditions for locally optimal solutions of minimax optimization problems with infinitely many constraints. Sufficient conditions for such solutions to the considered problem are also provided by introducing generalized convex functions defined in terms of the limiting subdifferential for locally Lipschitz functions. In addition, some duality results for minimax optimization problems with infinitely many constraints are also provided. Furthermore, we derive necessary and sufficient conditions for a weak Pareto solution to the multiobjective optimization problem. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate topographic anatomy of the footprints of key ligaments of the elbow and assess their relationships with bony parameters using micro-computed tomography (micro-CT). Additionally, the ratios of type I/III collagen at the medial collateral ligament (MCL) and lateral collateral ligament (LCL) of elbow were investigated. Methods: Eleven cadaveric elbows attached by both the MCL and LCL were scanned using micro-CT and reconstructed three-dimensionally. Additionally, the ligaments were examined under polarized light microscopy to determine the histological characteristics of collagen patterns. Results: Areas of footprints of the MCL and LCL attaching onto the humerus were 133.2±25.8 mm² and 128.3±23.2 mm², respectively. Footprint sizes of anterior and posterior bundles of the MCL in the proximal ulna and lateral ulnar collateral ligament (LUCL) attaching to the proximal ulna averaged to 109.9 mm², 89.2 mm², and 89.7 mm², respectively. There were a positive correlation between footprint size of the MCL and LUCL at the humeral side and a negative correlation between the footprint size of the MCL at humeral side and maximal diameter of the radial head. The collagen I/III ratio of the humeral attachment of the MCL was higher than distal attachment of the MCL. Conclusion: This study provides a better understanding of the pathologies of the MCL and LCL complex of the elbow and their relationships with osseous anatomy and may assist the clinician with an anatomic reconstruction of the ligaments. [ABSTRACT FROM AUTHOR]

Rapid advances in automotive applications led to need for big data transmission in vehicles. For these requirements, SOME/IP Transport Protocol(SOME/IP-TP) was proposed in SOME/IP(Scalable service-Oriented MiddlewarE over IP), which is a service-oriented vehicle communication. SOME/IP-TP is a method to segment a big data into lots of small-scaled smaller data. This makes it possible to transmit big data using UDP. In this paper, we analyzed the problem caused by connectionless and unreliable characteristics of UDP when using SOME/IP-TP. First, the abnormal transmission process of data due to each characteristic was investigated. Second, exceptions were defined as Shutdown and Missing, respectively. Finally, each exception was analyzed for message type transmitted through SOME/IP-TP. From the results, it was confirmed that unnecessary data transmission problems occurred when Shutdown of the Response message receiver or Missing of segmented data [ABSTRACT FROM AUTHOR]

Gait training is an important rehabilitation exercise for lower-extremity patients to recover their ability to walk. However, existing gait training that makes use of treadmills or robotic assistive systems differs from the actual walking environment on the ground because they repeat similar treatments in restricted treatment rooms. Therefore, in this paper, we propose a new type of gait training system that combines a mobile robot with virtual reality. The proposed system is a mobile system that augments virtual content for gait training on real ground. Our proposed system differs from conventional robotic-assisted gait training in terms of making a patient interact with the content. In addition, there is another advantage in that the space is not limited during gait training because a mobile robot is used. Two experiments were conducted, and the results were used to examine the performance of our proposed system. [ABSTRACT FROM AUTHOR]

Background: The virtual reality (VR) content market is rapidly growing due to an increased supply of VR devices such as head-mounted displays (HMDs), whereas VR sickness (reported to occur while experiencing VR) remains an unsolved problem. The most widely used method of reducing VR sickness is the use of a rest frame that stabilizes the user's viewpoint by providing fixed visual stimuli in VR content (including video). However, the earth-fixed grid and natural independent visual background that are widely used as rest frames cannot maintain VR fidelity, as they reduce the immersion and the presence of the user. A visual guide is a visual element (eg, a crosshair of first-person shooter [FPS]) that induces a user's gaze movement within the VR content while maintaining VR fidelity, whereas there are no studies on the correlation of visual guide with VR sickness. Objective: This study aimed to analyze the correlation between VR sickness and crosshair, which is widely used as a visual guide in FPS games. Methods: Eight experimental scenarios were designed and evaluated, including having the visual guide on/off, the game controller on/off, and varying the size and position of the visual guide to determine the effect of visual guide on VR sickness. Results: The results showed that VR sickness significantly decreased when visual guide was applied in an FPS game. In addition, VR sickness was lower when the visual guide was adjusted to 30% of the aspect ratio and positioned in the head-tracking direction. Conclusions: The experimental results of this study indicate that the visual guide can achieve VR sickness reduction while maintaining user presence and immersion in the virtual environment. In other words, the use of a visual guide is expected to solve the existing limitation of distributing various types of content due to VR sickness. [ABSTRACT FROM AUTHOR]

This study suggests a new way to modify the size and morphology of Al-Fe phases in modified AA 7075 by using an Fe-Mn solid solution powder as the precursor. When Fe and Mn are added in the form of a solid solution, the diffusion of Fe and Mn toward the Al is delayed, thus altering the chemical composition and morphology of the precipitates. The fine, spherical precipitates are found to provide a good balance between strength and ductility compared to the case where Fe and Mn are separately added. [ABSTRACT FROM AUTHOR]

Purpose: The most common surgical treatment for distal radius fracture is internal fixation using volar locking plates, but it is sometimes difficult to maintain reduction with them. Therefore, this research reports the results of surgical treatment with additional radial column plates. Methods: We analyzed 12-month follow-up results in 100 cases. The patients had the B or C types of distal radius fractures, in accordance with AO classification, and underwent surgical treatment at our hospital from May 2013 to December 2019. There were 16 cases of B-type and 84 cases of C-type fractures. Out of these, 87 were treated with volar locking plates (V group) and 13 had additional radial column plates (VR group). The results of surgical treatment were examined clinically by measuring the disabilities of the arm, shoulder and hand (DASH) and Mayo wrist score, and radiologically by measuring the radial length, radial inclination, and volar tilt, before and after surgery. Results: After treatment, the radiographic average in the V group showed a radial length of 12.3 mm, radial inclination of 20.2°, and volar tilt of 5.8°, while the VR group showed 11.6 mm, 22.3°, and 9.0° respectively. A statistically significant difference was found in the DASH score, and the DASH score showed good results in the VR group. Conclusion: Additional radial column plate fixation is worth considering because it provides clinically and radiologically satisfactory results in treatment of B and C types distal radius fracture involving articular surface. [ABSTRACT FROM AUTHOR]

OBJECTIVES　 To investigate the prevalence of potentially inappropriate prescribing (PIP) for cardiovascular system (CVS) and antiplatelet/anticoagulant (AP/AC) drugs among Korean elderly patients, using the Screening Tool of Older Persons’ Prescriptions (STOPP) criteria version 2 and to identify the risk factors related to PIP. METHODS　 The 2016 National Aged Patient Sample data, comprising National Health Insurance claim records for a random sample of 20% of patients aged ≥ 65 years, were used to calculate PIP prevalence of outpatient prescriptions. For criteria including drug-disease interactions, PIP prevalence per indication was estimated. RESULTS　 Among 1,274,148 elderly patients and 27,062,307 outpatient prescription claims, 100,085 patients (7.85%) and 341,664 claims (1.27%) had one or more PIP. The most frequent PIP was “non-steroidal anti-inflammatory drug with concurrent antiplatelet agent (s) without proton-pump inhibitor prophylaxis ” in the claim-level (0.97%) and patient-level (6.33%) analyses. “Betablocker with bradycardia ” (16.47% of claims) and “angiotensin receptor blockers in patients with hyperkalaemia ” (23.89% of claims) showed the highest PIP prevalence per indication. Logistic regression analysis revealed that, among the patient and health care provider characteristics, female, older age, more severe comorbidities, polypharmacy, higher level of healthcare organization, and specialty of prescriber were significantly associated with a higher risk of PIP. CONCLUSIONS　 Our findings of a high prevalence of PIP for CVS and AP/AC drugs among the elderly suggest that an effective strategy is urgently needed to improve the prescription practices of these drugs. [ABSTRACT FROM AUTHOR]

Background: Osteochondral lesion of the talus (OLT) is commonly found as a concomitant pathologic lesion in a large proportion of patients with chronic lateral ankle instability (CLAI). This study investigated which characteristics in a patient with CLAI increase the risk for OLT. Methods: Three hundred sixty-four patients who underwent a modified Brostrom operation for their CLAI were reviewed retrospectively. The characteristics of each patient and variables associated with OLTs were investigated. Statistical analyses were performed to determine the effect of each potential predictor on the incidence of OLT, and to evaluate the associations between the patient characteristics and variables associated with OLTs. Results: Patients with OLTs were more frequently female (female vs male: 63.1% vs 43.9%, P = .003). In addition, the lesion sizes were larger in female patients (female vs male: 113.9+24.9 mm² vs 100.7 + 18.0 mm², P = .002), and medial lesions were more common in female patients (female vs male; 93.3% vs 81.8%, P = .036). The lesion sizes were larger in patients with a wider talar tilt angle (P < .001), and patients with a medial OLT showed a wider talar tilt angle (12.0+2.0 degrees vs 10.3 + 2.2 degrees, P = .002). Conclusion: In this CLAI patient cohort, we found female patients to be at greater risk for OLTs than male patients. Furthermore, CLAI female patients with concomitant OLT had on average a larger lesion size, more frequent OLT medial position, and were associated with wider talar tilt angles, suggesting that females had more intrinsic ankle instability than males. [ABSTRACT FROM AUTHOR]