Risk of Subsequent Primary Cancers Among Adult-Onset 5-Year Cancer Survivors in South Korea: Retrospective Cohort Study.

BACKGROUND: The number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase. OBJECTIVE: We evaluated the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age. METHODS: We conducted a retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with an FPC in 2009 to 2010 and followed them until December 31, 2019. We measured the SPC incidence per 10,000 person-years and the standardized incidence ratio (SIR) compared with the incidence expected in the general population. RESULTS: Among 266,241 survivors (mean age at FPC: 55.7 years; 149,352/266,241, 56.1% women), 7348 SPCs occurred during 1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI 0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 of the 21 FPC types had a significantly lower risk of developing any SPCs. The risk of developing any SPC type differed by age; the risk was 28% higher in young (<40 years) cancer survivors (SIR 1.28, 95% CI 1.16-1.42; incidence: 30 per 10,000 person-years) and 27% lower in middle-aged and older (≥40 years) cancer survivors (SIR 0.73, 95% CI 0.71-0.74; incidence: 80 per 10,000 person-years) compared with the age-corresponding general population. The most common types of FPCs were mainly observed as SPCs in cancer survivors, with lung (21.6%) and prostate (15.2%) cancers in men and breast (18.9%) and lung (12.2%) cancers in women. The risks of brain cancer in colorectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidney cancer and leukemia in thyroid cancer survivors were significantly higher for both sexes. Other high-risk SPCs varied by FPC type and sex. Strong positive associations among smoking-related cancers, such as laryngeal, head and neck, lung, and esophageal cancers, were observed. Substantial variation existed in the associations between specific types of FPC and specific types of SPC risk, which may be linked to hereditary cancer syndrome: for women, the risks of ovarian cancer for breast cancer survivors and uterus cancers for colorectal cancer survivors, and for men, the risk of pancreas cancer for kidney cancer survivors. CONCLUSIONS: The varying risk for SPCs by age, sex, and FPC types in cancer survivors implies the necessity for tailored prevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essential to reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and prevention strategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs.

Smartphone-based combined oral and whole-body exercise programme aimed at improving oral functions: A randomized clinical trial.

OBJECTIVES: To investigate the effects of a smartphone-based oral and whole-body exercise programme on oral function in older adults. METHODS: Individuals aged 65 years or above were randomized into three groups (non-app use, app use and control group), and a combined oral and whole-body exercise programme was conducted for 5 weeks. Oral muscle strength, saliva flow rate, Oral Health Impact Profile-14 (OHIP-14), and Geriatric Oral Health Assessment Index (GOHAI) were measured before and after the intervention. The changes in each group were analysed at the end of the programme using paired sample t-tests, and the differences among the groups were analysed using the chi-square test, Fisher's exact test and ANOVA. RESULTS: The anterior tongue strength increased by 2.80 kPa after the intervention in the non-app use group; however, the change was not statistically significant. In the app use group, the anterior tongue strength significantly increased by 4.48 kPa. The saliva flow rate increased by 0.54 and 0.71 g/min in the non-app and app use groups, respectively, after the intervention (p < 0.05), and the change was greater in the app use group than in the other groups (p < 0.01). There were no significant changes in the posterior tongue strength, cheek strength, OHIP-14 or GOHAI scores over the course of the study. CONCLUSIONS: A smartphone-based combined oral and whole-body exercise programme can improve anterior tongue strength and saliva flow rate in older participants. The programme, however, did not result in significant changes in posterior tongue strength, cheek strength and perceived oral health.

Association Between Subjective Masticatory Function and Mild Cognitive Impairment in Older Adults.

AIM: This study aimed to examine the effect of subjective masticatory function on the occurrence of mild cognitive impairment (MCI) by analysing the Korean Longitudinal Study of Ageing (KLoSA) data. METHODS: The study participants were 2954 KLoSA participants aged 60 years or older in the first wave (2006) who had normal cognitive function. The subjective masticatory function was determined using a survey item, and the responses were grouped into 3 categories, ie, good, moderate, and poor. The occurrence of MCI in the 3 groups was followed up until 2020. Cognitive function was assessed based on the Korean Mini-Mental State Examination score. Age, sex, education level, residence, health insurance type, smoking status, drinking status, and the number of chronic diseases were considered as potential confounders. To examine the occurrence of MCI according to subjective masticatory function, Cox proportional hazard regression analysis was performed. RESULTS: Cox proportional hazard regression models adjusted for confounders yielded the following results: in men, the risk of MCI was higher in those whose subjective masticatory function was moderate and poor, as compared to those with good subjective masticatory function (adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 1.12-1.58; aHR, 1.23; 95% CI, 1.04-1.46). In contrast, in women, subjective masticatory function did not significantly influence the occurrence of MCI (aHR, 1.05; 95% CI, 0.89-1.24; aHR, 1.08; 95% CI, 0.92-1.28). CONCLUSIONS: This study suggests that poor masticatory function may be a risk factor for MCI in older men.

Elevating Low-Grade Heat Harvesting with Daytime Radiative Cooling and Solar Heating in Thermally Regenerative Electrochemical Cycles.

Thermal radiation control has garnered growing interest for its ability to provide localized cooling and heating without energy consumption. However, its direct application for energy harvesting remains largely underexplored. In this work, we demonstrate a novel system that leverages daytime radiative cooling and solar heating technologies to continuously power charging-free thermally regenerative electrochemical cycle (TREC) devices, turning ubiquitous low-grade ambient heat into electricity. Notably, by harnessing a substantial 35 °C temperature differential solely through passive cooling and heating effects, the integrated system exhibits a cell voltage of 50 mV and a specific capacity exceeding 20 mAh g-1 of PB. This work unlocks the potential of readily available low-grade ambient heat for sustainable electricity generation.

Prognostic and predictive impact of sex in locally advanced microsatellite instability high gastric or gastroesophageal junction cancer: An individual patient data pooled analysis of randomized clinical trials.

BACKGROUND: Surgery plus peri-operative/adjuvant chemotherapy is the standard of care for locally advanced GC/GEJC, though with unsatisfactory results. dMMR/MSI-high tumors have better prognosis and scant benefit from chemotherapy as compared to pMMR/MSS ones. The differential outcome of therapies in terms of safety and efficacy according to sex is still debated in GC/GEJC patients. METHODS: We previously performed an individual patient data pooled analysis of MAGIC, CLASSIC, ITACA-S, and ARTIST trials including GC/GEJC patients treated with surgery alone or surgery plus peri-operative/adjuvant chemotherapy to assess the value of MSI status. We performed a secondary analysis investigating the prognostic and predictive role of sex (female versus male) in the pooled analysis dataset in the overall population and patients stratified for MSI status (MSI-high versus MSS/MSI-low). Disease-free (DFS) and overall survival (OS) were calculated. RESULTS: Patients with MSI-high tumors had improved survival as compared to MSS/MSI-low ones irrespective of sex, whereas in those with MSS/MSI-low tumors, females had numerically longer OS and DFS (5-year OS was 63.2% versus 57.6%, HR 0.842; p = 0.058, and 5-year DFS was 55.8% versus 50.8%, HR 0.850; p = 0.0504 in female versus male patients). The numerical difference for the detrimental effect of chemotherapy in MSI-high GC was higher in females than males, while the significant benefit of chemotherapy over surgery alone was confirmed in MSS/MSI-low GC irrespective of sex. CONCLUSIONS: This pooled analysis including four randomized trials highlights a relevant impact of sex in the prognosis and treatment efficacy of MSI-high and MSS/MSI-low non-metastatic GC/GEJC.

Synergistic Effect of Electrical and Biochemical Stimulation on Human iPSC-Derived Neural Differentiation in a Microfluidic Electrode Array Chip.

Neural differentiation is crucial for advancing our understanding of the nervous system and developing treatments for neurological disorders. The advanced methods and the ability to manipulate the alignment, proliferation, and differentiation of stem cells are essential for studying neuronal development and synaptic interactions. However, the utilization of human induced pluripotent stem cells (iPSCs) for disease modeling of neurodegenerative conditions may be constrained by the prolonged duration and uncontrolled cell differentiation required for functional neural cell differentiation. Here, we developed a microfluidic chip to enhance the differentiation and maturation of specific neural lineages by placing aligned microelectrodes on the glass surface to regulate the neural differentiation of human iPSCs. The utilization of electrical stimulation (ES) in conjunction with neurotrophic factors (NF) significantly enhanced the efficiency in generating functional neurons from human iPSCs. We also observed that the simultaneous application of NF and ES to human iPSCs promoted their differentiation and maturation into functional neurons while increasing synaptic interactions. Our research demonstrated the effect of combining NF and ES on human iPSC-derived neural differentiation.

Effect of gut microbiota-derived metabolites and extracellular vesicles on neurodegenerative disease in a gut-brain axis chip.

A new perspective suggests that a dynamic bidirectional communication system, often referred to as the microbiome-gut-brain axis, exists among the gut, its microbiome, and the central nervous system (CNS). This system may influence brain health and various brain-related diseases, especially in the realms of neurodevelopmental and neurodegenerative conditions. However, the exact mechanism is not yet understood. Metabolites or extracellular vesicles derived from microbes in the gut have the capacity to traverse the intestinal epithelial barrier or blood-brain barrier, gaining access to the systemic circulation. This phenomenon can initiate the physiological responses that directly or indirectly impact the CNS and its function. However, reliable and controllable tools are required to demonstrate the causal effects of gut microbial-derived substances on neurogenesis and neurodegenerative diseases. The integration of microfluidics enhances scientific research by providing advanced in vitro engineering models. In this study, we investigated the impact of microbe-derived metabolites and exosomes on neurodevelopment and neurodegenerative disorders using human induced pluripotent stem cells (iPSCs)-derived neurons in a gut-brain axis chip. While strain-specific, our findings indicate that both microbial-derived metabolites and exosomes exert the significant effects on neural growth, maturation, and synaptic plasticity. Therefore, our results suggest that metabolites and exosomes derived from microbes hold promise as potential candidates and strategies for addressing neurodevelopmental and neurodegenerative disorders.

The short-term effect of ambient particulate matter on suicide death.

BACKGROUND: Air pollution can cause various respiratory and neurological diseases and continuous exposure can lead to death. Previous studies have reported that particulate matter (PM) exposure increases the risk of depression, suicidal thoughts, and suicidal death; however, the results are inconsistent and limited. This study aimed to examine the relationship between short-term PM exposure and suicide deaths, as well as investigate the short-term effects of PM on suicide death within vulnerable groups based on factors such as sex, age group, suicide-related information (note, method, and cause), psychiatric disorders, and physical diseases. METHODS: Data on a total of 28,670 suicide deaths from 2013 to 2017, provided by the Korea Foundation for Suicide Prevention, were analyzed. The study design employed a time-series analysis with a two-stage approach. In the first step, a generalized additive model combined with a distributed lag nonlinear model was used to estimate the short-term effect of PM exposure on suicide risk specific to each city. In the second step, the estimated results from each city were pooled through a meta-analysis to derive the overall effect. We determined the effects of single lag, cumulative lag, and moving average PM concentrations from days 0-7 before suicide. RESULTS: We confirmed an association between exposure to PM10 (≤ 10 µm in diameter) and deaths due to suicide. In particular, among individuals with psychiatric disorders and those who employed non-violent suicide methods, increased exposure to PM10 was associated with a higher risk of death by suicide, with percentage changes of 5.92 (95% confidence interval [CI]: 3.95-7.92) and 11.47 (95% CI: 7.95-15.11), respectively. Furthermore, in the group with psychiatric disorders, there was an observed tendency of increasing suicide risk as PM10 levels increased up to 120 µg/m3, whereas in the group with non-violent suicide deaths, there was a pronounced trend of rapid increase in suicide risk with an increase in PM10 up to 100 µg/m3. CONCLUSIONS: These results show an association between short-term exposure to PM and suicide. Our study adds evidence for the benefits of reducing PM in preventing diseases and improving mental health.

Defect Engineering of WO3 by Rapid Flame Reduction for Efficient Photoelectrochemical Conversion of Methane into Liquid Oxygenates.

Photoelectrochemical (PEC) conversion is a promising way to use methane (CH4) as a chemical building block without harsh conditions. However, the PEC conversion of CH4 to value-added chemicals remains challenging due to the thermodynamically favorable overoxidation of CH4. Here, we report WO3 nanotube (NT) photoelectrocatalysts for PEC CH4 conversion with high liquid product selectivity through defect engineering. By tuning the flame reduction treatment, we carefully controlled the oxygen vacancies of WO3 NTs. The optimally reduced WO3 NTs suppressed overoxidation of CH4 showing a high total C1 liquid selectivity of 69.4% and a production rate of 0.174 µmol cm-2 h-1. Scanning electrochemical microscopy revealed that oxygen vacancies can restrain the production of hydroxyl radicals, which, in excess, could further oxidize C1 intermediates to CO2. Additionally, band diagram analysis and computational studies elucidated that oxygen vacancies thermodynamically suppress overoxidation. This work introduces a strategy for understanding and controlling the selectivity of photoelectrocatalysts for direct conversion of CH4 to liquids.

Functional Brain Networks to Evaluate Treatment Responses in Parkinson's Disease.

Network analysis of functional brain scans acquired with [18F]-fluorodeoxyglucose positron emission tomography (FDG PET, to map cerebral glucose metabolism), or resting-state functional magnetic resonance imaging (rs-fMRI, to map blood oxygen level-dependent brain activity) has increasingly been used to identify and validate reproducible circuit abnormalities associated with neurodegenerative disorders such as Parkinson's disease (PD). In addition to serving as imaging markers of the underlying disease process, these networks can be used singly or in combination as an adjunct to clinical diagnosis and as a screening tool for therapeutics trials. Disease networks can also be used to measure rates of progression in natural history studies and to assess treatment responses in individual subjects. Recent imaging studies in PD subjects scanned before and after treatment have revealed therapeutic effects beyond the modulation of established disease networks. Rather, other mechanisms of action may be at play, such as the induction of novel functional brain networks directly by treatment. To date, specific treatment-induced networks have been described in association with novel interventions for PD such as subthalamic adeno-associated virus glutamic acid decarboxylase (AAV2-GAD) gene therapy, as well as sham surgery or oral placebo under blinded conditions. Indeed, changes in the expression of these networks with treatment have been found to correlate consistently with clinical outcome. In aggregate, these attributes suggest a role for functional brain networks as biomarkers in future clinical trials.

The clinical effectiveness of fused image of single-photon emission CT and facial CT for the evaluation of degenerative change of mandibular condylar head.

BACKGROUND: The primary objective of this study was to assess the clinical effectiveness of fused images obtained from single-photon emission computed tomography (SPECT) and facial computed tomography (CT) for evaluating degenerative changes in the mandibular condylar head. This assessment was accomplished by comparing the Technetium-99 m methylene diphosphonate (99mTc-MDP) uptake ratio with the results of clinical and radiographic findings. METHODS: The study included 17 patients (3 males and 14 females) with suspected osteoarthritis of the mandibular condyle, totaling 34 temporomandibular joints (TMJs). Based on clinical and radiographic examinations, the TMJs were categorized into four groups: normal (group N), internal derangement (group ID), osteoarthritis (group OA), and osteoarthritis sequelae (group OAseq). For each patient, bone SPECT and facial CT scans were registered and reconstructed to create fused SPECT/CT images. The 99mTc-MDP uptake levels in the TMJs were statistically compared among the four groups. RESULTS: The 99mTc-MDP uptake ratio showed a gradual increase in the order of the following: group N, group OAseq, group ID, and group OA. There was a significant difference observed among groups (p = 0.003), mainly driven by the disparity between group OA and both group N (p < 0.001) and group OAseq (p = 0.048). CONCLUSION: Fused SPECT/CT image can be an effective tool for evaluating degenerative changes in the mandibular condylar head. The technique demonstrated the ability to differentiate between normal TMJs and those with internal derangement, osteoarthritis, or osteoarthritis sequelae. This approach holds promise as a valuable method in clinical assessments of TMJ degeneration.

Genomic and evolutionary characteristics of metastatic gastric cancer by routes.

BACKGROUND: In gastric cancer (GC) patients, metastatic progression through the lymphatic, hematogenous, peritoneal, and ovarian routes, is the ultimate cause of death. However, the genomic and evolutionary characteristics of metastatic GC have not been widely evaluated. METHODS: Whole-exome sequencing data were analyzed for 99 primary and paired metastatic gastric cancers from 15 patients who underwent gastrectomy and metastasectomy. RESULTS: Hematogenous metastatic tumors were associated with increased chromosomal instability and de novo gain/amplification in cancer driver genes, whereas peritoneal/ovarian metastasis was linked to sustained chromosomal stability and de novo somatic mutations in driver genes. The genomic distance of the hematogenous and peritoneal metastatic tumors was found to be closer to the primary tumors than lymph node (LN) metastasis, while ovarian metastasis was closer to LN and peritoneal metastasis than the primary tumor. Two migration patterns for metastatic GCs were identified; branched and diaspora. Both molecular subtypes of the metastatic tumors, rather than the primary tumor, and their migration patterns were related to patient survival. CONCLUSIONS: Genomic characteristics of metastatic gastric cancer is distinctive by routes and associated with patients' prognosis along with genomic evolution pattenrs, indicating that both primary and metastatic gastric cancers require genomic evaluation.

Clinical molecular subtyping reveals intrinsic mesenchymal reprogramming in gastric cancer cells.

The mesenchymal cancer phenotype is known to be clinically related to treatment resistance and a poor prognosis. We identified gene signature-based molecular subtypes of gastric cancer (GC, n = 547) based on transcriptome data and validated their prognostic and predictive utility in multiple external cohorts. We subsequently examined their associations with tumor microenvironment (TME) features by employing cellular deconvolution methods and sequencing isolated GC populations. We further performed spatial transcriptomics analysis and immunohistochemistry, demonstrating the presence of GC cells in a partial epithelial-mesenchymal transition state. We performed network and pharmacogenomic database analyses to identify TGF-ß signaling as a driver pathway and, thus, a therapeutic target. We further validated its expression in tumor cells in preclinical models and a single-cell dataset. Finally, we demonstrated that inhibition of TGF-ß signaling negated mesenchymal/stem-like behavior and therapy resistance in GC cell lines and mouse xenograft models. In summary, we show that the mesenchymal GC phenotype could be driven by epithelial cancer cell-intrinsic TGF-ß signaling and propose therapeutic strategies based on targeting the tumor-intrinsic mesenchymal reprogramming of medically intractable GC.

Effect of gut microbiome-derived metabolites and extracellular vesicles on hepatocyte functions in a gut-liver axis chip.

Metabolism, is a complex process involving the gut and the liver tissue, is difficult to be reproduced in vitro with conventional single cell culture systems. To tackle this challenge, we developed a gut-liver-axis chip consisting of the gut epithelial cell chamber and three-dimensional (3D) uniform-sized liver spheroid chamber. Two cell culture chamber compartments were separated with a porous membrane to prevent microorganisms from passing through the chamber. When the hepG2 spheroids cultured with microbiota-derived metabolites, we observed the changes in the physiological function of hepG2 spheroids, showing that the albumin and urea secretion activity of liver spheroids was significantly enhanced. Additionally, the functional validation of hepG2 spheroids treated with microbiota-derived exosome was evaluated that the treatment of the microbiota-derived exosome significantly enhanced albumin and urea in hepG2 spheroids in a gut-liver axis chip. Therefore, this gut-liver axis chip could be a potentially powerful co-culture platform to study the interaction of microbiota and host cells.

Humanlike spontaneous motion coordination of robotic fingers through spatial multi-input spike signal multiplexing.

With advances in robotic technology, the complexity of control of robot has been increasing owing to fundamental signal bottlenecks and limited expressible logic state of the von Neumann architecture. Here, we demonstrate coordinated movement by a fully parallel-processable synaptic array with reduced control complexity. The synaptic array was fabricated by connecting eight ion-gel-based synaptic transistors to an ion gel dielectric. Parallel signal processing and multi-actuation control could be achieved by modulating the ionic movement. Through the integration of the synaptic array and a robotic hand, coordinated movement of the fingers was achieved with reduced control complexity by exploiting the advantages of parallel multiplexing and analog logic. The proposed synaptic control system provides considerable scope for the advancement of robotic control systems.

Multiplexed Complementary Signal Transmission for a Self-Regulating Artificial Nervous System.

Neuromorphic engineering has emerged as a promising research field that can enable efficient and sophisticated signal transmission by mimicking the biological nervous system. This paper presents an artificial nervous system capable of facile self-regulation via multiplexed complementary signals. Based on the tunable nature of the Schottky barrier of a complementary signal integration circuit, a pair of complementary signals is successfully integrated to realize efficient signal transmission. As a proof of concept, a feedback-based blood glucose level control system is constructed by incorporating a glucose/insulin sensor, a complementary signal integration circuit, an artificial synapse, and an artificial neuron circuit. Certain amounts of glucose and insulin in the initial state are detected by each sensor and reflected as positive and negative amplitudes of the multiplexed presynaptic pulses, respectively. Subsequently, the pulses are converted to postsynaptic current, which triggered the injection of glucose or insulin in a way that confined the glucose level to a desirable range. The proposed artificial nervous system demonstrates the notable potential of practical advances in complementary control engineering.

Adaptive and pathological connectivity responses in Parkinson's disease brain networks.

Functional imaging has been used extensively to identify and validate disease-specific networks as biomarkers in neurodegenerative disorders. It is not known, however, whether the connectivity patterns in these networks differ with disease progression compared to the beneficial adaptations that may also occur over time. To distinguish the 2 responses, we focused on assortativity, the tendency for network connections to link nodes with similar properties. High assortativity is associated with unstable, inefficient flow through the network. Low assortativity, by contrast, involves more diverse connections that are also more robust and efficient. We found that in Parkinson's disease (PD), network assortativity increased over time. Assoratitivty was high in clinically aggressive genetic variants but was low for genes associated with slow progression. Dopaminergic treatment increased assortativity despite improving motor symptoms, but subthalamic gene therapy, which remodels PD networks, reduced this measure compared to sham surgery. Stereotyped changes in connectivity patterns underlie disease progression and treatment responses in PD networks.

Effectiveness of an oral health education programme using a mobile application for older adults: A randomised clinical trial.

OBJECTIVE: To investigate the effectiveness of an oral health education programme using a mobile app for adults aged 65 years or older. METHODS: Participants aged 65 or older were randomly allocated into non-app use (n = 25), app use (n = 22) and control (n = 26) groups. The non-app use group received lecture-based oral health education using PowerPoint presentations and participated in workbook activities twice a week for five weeks, whereas the app use group underwent oral health education using a smartphone app and workbook activities for five weeks. Before and after the intervention, a questionnaire survey and oral health examination were performed to examine changes in oral health-related indices. RESULTS: The non-app use group showed significant changes, with a 2.1 increase in oral health knowledge score, 0.2 decrease in the O'Leary index and 0.6 decrease in tongue coating. The app use group showed significant changes, with a 3.1 increase in oral health knowledge score, a 2.5 increase in oral health perception, a 0.3 decrease in the O'Leary index and a 1.4 decrease in tongue coating. Repeated-measures ANOVA showed that interaction between time and group was significant only in tongue coating variable. CONCLUSION: The smartphone app developed in this study carries the possibility to convey informative content for oral health education among older adults.