High-throughput organo-on-pillar (high-TOP) array system for three-dimensional ex vivo drug testing.

The development of organoid culture technologies has triggered industrial interest in ex vivo drug test-guided clinical response prediction for precision cancer therapy. The three-dimensional culture encapsulated with basement membrane (BM) components is extremely important in establishing ex vivo organoids and drug sensitivity tests because the BM components confer essential structures resembling tumor histopathology. Although numerous studies have demonstrated three-dimensional culture-based drug screening methods, establishing a large-scale drug-screening platform with matrix-encapsulated tumor cells is challenging because the arrangement of microspots of a matrix-cell droplet onto each well of a microwell plate is inconsistent and difficult to standardize. In addition, relatively low scales and lack of reproducibility discourage the application of three-dimensional organoid-based drug screening data for precision treatment or drug discovery. To overcome these limitations, we manufactured an automated organospotter-integrated high-throughput organo-on-pillar (high-TOP) drug-screening platform. Our system is compatible with various extracellular matrices, including BM extract, Matrigel, collagen, and hydrogel. In addition, it can be readily utilized for high-content analyses by simply exchanging the bottom plates without disrupting the domes. Our system demonstrated considerable robustness, consistency, reproducibility, and biological relevancy in three-dimensional drug sensitivity analyses using Matrigel-encapsulated ovarian cancer cell lines. We also demonstrated proof-of-concept cases representing the clinical feasibility of high-TOP-assisted ex vivo drug tests linked to clinical chemo-response in ovarian cancer patients. In conclusion, our platform provides an automated and standardized method for ex vivo drug-sensitivity-guided clinical response prediction, suggesting effective chemotherapy regimens for patients with cancer.

Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2019.

PURPOSE: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2019. MATERIALS AND METHODS: Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2019, with survival follow-up until December 31, 2020. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea. RESULTS: In 2019, newly diagnosed cancer cases and deaths from cancer were reported as 254,718 (ASR, 275.4 per 100,000) and 81,203 (ASR, 72.2 per 100,000), respectively. For the first time, lung cancer (n=29,960) became the most frequent cancer in Korea, excluding thyroid cancer. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.3% annually from 2012 to 2015, thereafter, followed by nonsignificant changes. The incidence of thyroid cancer increased again from 2016 (annual percentage change, 6.2%). Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years (annual decrease of 2.7% from 2002 to 2013; 3.3% from 2013 to 2019). The 5-year relative survival between 2015 and 2019 was 70.7%, which contributed to prevalent cases reaching over 2 million in 2019. CONCLUSION: Cancer survival rates have improved over the past decades, but the number of newly diagnosed cancers is still increasing, with some cancers showing only marginal improvement in survival outcomes. As the number of cancer survivors increases, a comprehensive cancer control strategy should be implemented in line with the changing aspects of cancer statistics.

Comparison of the effects of corticosteroid and hyaluronic acid-carboxymethylcellulose solution on selective nerve root block for lumbar radiculopathy: A prospective, double-blind, randomized controlled clinical trial.

BACKGROUND: Selective nerve root block (SNRB) was shown to effectively control radiating pain and reduce the need for surgical intervention. However, repetitive injections may trigger corticosteroid-induced side effects (hypercorticism, hyperglycemia, or fluid retention). This study aims to compare the potency of hyaluronic acid-carboxymethylcellulose (HA-CMC) solution versus that of corticosteroids regarding lower leg radiating pain (LLRP) improvement and functional outcome. METHODS: Among 128 patients, 44 patients who complain about having LLRP due to lumbar spinal stenosis and do not have neurological symptoms requiring surgery were enrolled for this study. Group A with 22 patients injected with cocktail A (local anesthetics and corticosteroid) and group B with 22 patients injected with cocktail B (local anesthetics and HA-CMC). Outcome measures were the visual analog scale (VAS), Oswestry Disability Index (ODI), and short form-36 (SF-36). All patients were asked to fill in the questionnaires during the follow-up assessment period at 3 days, 7 days, 2 weeks, 6 weeks, and 12 weeks. RESULTS: In all time periods, there were no statistical differences between the two groups for VAS scores and VAS improvement over time, ODI scores and ODI improvement over time, and SF-36 PCS scores and SF-36 mental component score scores. Additionally, the 95% confidence interval of the difference in VAS score improvement between the 2 groups in all time periods was within VAS 5.0, which is the minimum clinically relevant difference. CONCLUSIONS: Considering the adverse effects of corticosteroids, and the similar LLRP improvements, functional outcome, and quality of life, the HA-CMC solution may be an alternative option to corticosteroid in SNRB.

Amoxicillin or tetracycline in bismuth-containing quadruple therapy as first-line treatment for Helicobacter pylori infection.

AIM: To compare the efficacy and safety between modified quadruple- and bismuth-containing quadruple therapy as first-line eradication regimen for Helicobacter pylori infection. METHODS: This study was a multicenter, randomized-controlled, non-inferiority trial. Subjects endoscopically diagnosed with H. pylori infection were randomly allocated to receive modified quadruple- (rabeprazole 20 mg bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid [elemental bismuth 480 mg]; PAMB) or bismuth-containing quadruple therapy (rabeprazole 20 mg bid, bismuth subcitrate 300 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid; PBMT) for 14 days. Rates of eradication success and adverse events were investigated. Antibiotic resistance was determined using the agar dilution and DNA sequencing of the clarithromycin resistance point mutations in the 23 S rRNA gene of H. pylori. RESULTS: In total, 233 participants were randomized, 27 were lost to follow-up, and four violated the protocol. Both regimens showed an acceptable eradication rate in the intention-to-treat (PAMB: 87.2% vs. PBMT: 82.8%, P = .37), modified intention-to-treat (96.2% vs. 96%, P > .99), and per-protocol (96.2% vs. 96.9%, P > .99) analyses. Non-inferiority in the eradication success between PAMB and PBMT was confirmed. The amoxicillin-, metronidazole-, tetracycline-, clarithromycin-, and levofloxacin-resistance rates were 8.3, 40, 9.4, 23.5, and 42.2%, respectively. Antimicrobial resistance did not significantly affect the efficacy of either therapy. Overall compliance was 98.1%. Adverse events were not significantly different between the two therapies. CONCLUSION: Modified quadruple therapy comprising rabeprazole, amoxicillin, metronidazole, and bismuth is an effective first-line treatment for the H. pylori infection in regions with high clarithromycin and metronidazole resistance.

Neural correlates of motor imagery for elite archers.

Motor imagery is a mental rehearsal of simple or complex motor acts without overt body movement. It has been proposed that the association between performance and the mental rehearsal period that precedes the voluntary movement is an important point of difference between highly trained athletes and beginners. We compared the activation maps of elite archers and nonarchers during mental rehearsal of archery to test whether the neural correlates of elite archers were more focused and efficiently organised than those of nonarchers. Brain activation was measured using functional MRI in 18 right-handed elite archers and 18 right-handed nonarchers. During the active functional MRI imagery task, the participants were instructed to mentally rehearse their archery shooting from a first-person perspective. The active imagery condition was tested against the nonmotor imagery task as a control condition. The results showed that the premotor and supplementary motor areas, and the inferior frontal region, basal ganglia and cerebellum, were active in nonarchers, whereas elite archers showed activation primarily in the supplementary motor areas. In particular, our result of higher cerebellar activity in nonarchers indicates the increased participation of the cerebellum in nonarchers when learning an unfamiliar archery task. Therefore, the difference in cerebellar activation between archers and nonarchers provides evidence of the expertise effect in the mental rehearsal of archery. In conclusion, the relative economy in the cortical processes of elite archers could contribute to greater consistency in performing the specific challenge in which they are highly practised.

Neuroplastic changes within the brains of manganese-exposed welders: recruiting additional neural resources for successful motor performance.

BACKGROUND: In a previous study, regional delivery of manganese (Mn)ions within the brain revealed that the metal accumulates in the basal ganglia, where it induces degeneration of the globus pallidus. Degeneration of the basal ganglia impairs motor ability by compromising an important neural circuit involved in the regulation of motor control. Therefore, much research has been devoted to identifying a sensitive and non-invasive imaging marker to evaluate the functional correlates of Mn-related brain dysfunction. METHODS: We performed the first-ever sequential finger-tapping functional MRI (fMRI) experiment to investigate the behavioural significance of additionally recruited brain regions in welders with chronic Mn exposure. RESULTS: During the finger tapping task, activation of the bilateral primary sensorimotor cortex (SM1), bilateral supplementary motor area (SMA), bilateral dorsolateral premotor cortex, bilateral superior parietal cortex and ipsilateral dentate nucleus was higher in the welding group (42 welders) than in the control group (26 controls). The pallidal index correlated with the activation observed in the contralateral SM1 for the finger tapping task of the left hand. The fMRI variables correlated with motor behaviour. Grooved Pegboard performances (right hand) correlated with activation, as seen in the ipsilateral and contralateral SMAs obtained during the finger tapping task of the right hand. CONCLUSION: Our findings suggest that increased brain activation results from the compensational activation of ancillary cortical pathways, which ensures adequate motor function.