Comparative Effectiveness of the Revised American Joint Committee on Cancer Staging System.

The American Joint Committee on Cancer (AJCC) staging manual is periodically updated. This study aims to examine the staging performances in delineating stage-specific survival curves and to evaluate the reclassification of cases based on the 7th and 8th AJCC editions in Taiwan. Data were sourced from the Taiwan Cancer Registry for cases diagnosed in 2017 (7th edition) and 2018 (8th edition), each with a 2-year follow-up period. Performance was assessed using the area under the receiver operating characteristic curve and the Lorenz curve-derived Gini index, along with 2-year survival rates for evaluating patient prognoses. The 8th edition showed superior staging in four specific cancer types. Oropharyngeal cancer exhibited more variable 2-year survival rates across stages, and liver cancer showed a clearer decline in survival rates with advancing stages. The 8th edition also improved prognostic staging for non-small cell lung cancer and reclassified 26.4% of stage 4 prostate cancer patients under the 7th edition into stages 3 or 4A, showing 2-year survival rates above 90%. Our study highlights the 8th edition's refined capacity for stage-specific survival distinctions and reclassification of cases to enhance prognostication in certain cancers within Taiwan. We recommend a comprehensive evaluation when adopting a new edition or version.

Polarization-Switchable Electrochemistry of 2D Layered Bi2O2Se Bifunctional Microreactors by Ferroelectric Modulation.

Ferroelectric catalysts are known for altering surface catalytic activities by changing the direction of their electric polarizations. This study demonstrates polarization-switchable electrochemistry using layered bismuth oxyselenide (L-Bi2O2Se) bifunctional microreactors through ferroelectric modulation. A selective-area ionic liquid gating is developed with precise control over the spatial distribution of the dipole orientation of L-Bi2O2Se. On-chip microreactors with upward polarization favor the oxygen evolution reaction, whereas those with downward polarization prefer the hydrogen evolution reaction. The microscopic origin behind polarization-switchable electrochemistry primarily stems from enhanced surface adsorption and reduced energy barriers for reactions, as examined by nanoscale scanning electrochemical cell microscopy. Integrating a pair of L-Bi2O2Se microreactors consisting of upward or downward polarizations demonstrates overall water splitting in a full-cell configuration based on a bifunctional catalyst. The ability to modulate surface polarizations on a single catalyst via ferroelectric polarization switching offers a pathway for designing catalysts for water splitting.

Manipulating Ferroelectric Polarization and Spin Polarization of 2D CuInP2S6 Crystals for Photocatalytic CO2 Reduction.

Manipulating electronic polarizations such as ferroelectric or spin polarizations has recently emerged as an effective strategy for enhancing the efficiency of photocatalytic reactions. This study demonstrates the control of electronic polarizations modulated by ferroelectric and magnetic approaches within a two-dimensional (2D) layered crystal of copper indium thiophosphate (CuInP2S6) to boost the photocatalytic reduction of CO2. We investigate the substantial influence of ferroelectric polarization on the photocatalytic CO2 reduction efficiency, utilizing the ferroelectric-paraelectric phase transition and polarization alignment through electrical poling. Additionally, we explore enhancing the CO2 reduction efficiency by harnessing spin electrons through the synergistic introduction of sulfur vacancies and applying a magnetic field. Several advanced characterization techniques, including piezoresponse force microscopy, ultrafast pump-probe spectroscopy, in situ X-ray absorption spectroscopy, and in situ diffuse reflectance infrared Fourier transformed spectroscopy, are performed to unveil the underlying mechanism of the enhanced photocatalytic CO2 reduction. These findings pave the way for manipulating electronic polarizations regulated through ferroelectric or magnetic modulations in 2D layered materials to advance the efficiency of photocatalytic CO2 reduction.

Secular Increasing Trends in Female Thyroid Cancer Incidence in Taiwan.

BACKGROUND: Thyroid cancer incidence has increased globally in recent decades, especially in females, although its trends in Taiwan have not been studied extensively. This study aimed to investigate changes in female incidence and possible causes of thyroid cancer in Taiwan. METHODS: Using the Taiwan Cancer Registry (TCR) Database, age-standardized incidence rates, age-specific incidence rates and birth cohorts were calculated. Correlation between female thyroid cancer incidence and cohort fertility rates were examined. RESULTS: Thyroid cancer incidence increased in Taiwanese female, with age-adjusted rates per 100,000 people increasing from 7.37 during 1995-1999 to 20.53 during 2015-2019; the annual percentage change (APC) was 5.9% (95% CI, 5.3-6.5). Age-specific incidence rates increased with age, with peak rates occurring at younger ages. The APCs in the 50-54 age group were the highest (6.8%, 95% CI, 6.1-7.5). Incidence rates also increased with later birth cohorts. We observed a significant negative correlation between thyroid cancer incidence and fertility rates in the same birth cohort. CONCLUSIONS: We hypothesize that overdiagnosis may be a main reason for the rapidly increasing thyroid cancer incidence in Taiwanese females. Notably, we observed a strong negative correlation between fertility and thyroid cancer incidence. However, our study is limited by the absence of individual-level cancer data in the TCR database. These associations with fertility will be an important subject for future thyroid cancer research.

High-throughput screen identifies non inflammatory small molecule inducers of trained immunity.

Trained immunity is characterized by epigenetic and metabolic reprogramming in response to specific stimuli. This rewiring can result in increased cytokine and effector responses to pathogenic challenges, providing nonspecific protection against disease. It may also improve immune responses to established immunotherapeutics and vaccines. Despite its promise for next-generation therapeutic design, most current understanding and experimentation is conducted with complex and heterogeneous biologically derived molecules, such as ß-glucan or the Bacillus Calmette-Guérin (BCG) vaccine. This limited collection of training compounds also limits the study of the genes most involved in training responses as each molecule has both training and nontraining effects. Small molecules with tunable pharmacokinetics and delivery modalities would both assist in the study of trained immunity and its future applications. To identify small molecule inducers of trained immunity, we screened a library of 2,000 drugs and drug-like compounds. Identification of well-defined compounds can improve our understanding of innate immune memory and broaden the scope of its clinical applications. We identified over two dozen small molecules in several chemical classes that induce a training phenotype in the absence of initial immune activation-a current limitation of reported inducers of training. A surprising result was the identification of glucocorticoids, traditionally considered immunosuppressive, providing an unprecedented link between glucocorticoids and trained innate immunity. We chose seven of these top candidates to characterize and establish training activity in vivo. In this work, we expand the number of compounds known to induce trained immunity, creating alternative avenues for studying and applying innate immune training.

The utility of microbiome (microbiota) and exosomes in dentistry.

The concept of the oral-systemic link is important in both basic and clinical dentistry. The microbiome (microbiota) and exosomes are two prevalent issues in the modern medical researches. The common advent of oral and general microbiological investigation originated from the initial observations of oral bacteria within the dental plaque known as oral microbiome. In addition to oral diseases related to oral microbiome, the disruption of the oral and intestinal microbiome could result in the onset of systemic diseases. In the past decade, the exosomes have emerged in the field of the medical researches as they play a role in regulating the transport of intracellular vesicles. However, with the rapid advancement of exosomes researches in recent years, oral tissues (such as dental pulp stem cells and salivary gland cells) are used as the research materials to further promote the development of regenerative medicine. This article emphasized the importance of the concept of the oral-systemic link through the examples of microbiome (microbiota) and exosomes. Through the researches related to microbiome (microbiota) and exosomes, many evidences showed that as the basic dentistry developed directly from the assistance of the basic medicine, indirectly the progress of the basic dentistry turns back to promote the development of the basic medicine, indicating the importance of the concept of the oral-systemic link. The understanding of the oral-systemic link is essential for both clinicians and medical researchers, regardless of their dental backgrounds.

Ethnicity, gender, and geographical distribution of dentists in Taiwan in 1939 (Showa 14).

Background/purpose: Taiwan's dentistry entered into a new era of modernization and flourished during the Japanese colonial period. However, we know very little about the composition of dentists at that time. This study attempted to analyze the ethnicity, gender, and geographical distribution of dentists in Taiwan in 1939 (Showa 14). Materials and methods: The methods of documentary analysis and secondary data analysis were adopted to find the composition of dentists during the late Japanese colonial period through a name list of contract dentists for the Postal Savings Insurance published in August 1939 (Showa 14) by the Taiwan Government Transportation Department Information Bureau. Results: The total number of contract dentists was 368, accounting for 86.79% of the 424 practicing dentists in Taiwan in 1939 (Showa 14). Of the 368 contract dentists (328 males and 40 females), 225 (61.14%) were Taiwanese and 143 (38.86%) were Japanese. Among the 8 prefectures in Taiwan, Tainan Prefecture had the largest number of dentists (97), followed by Taipei (84) and Taichung (78) prefectures. The number of contract dentists per 100,000 people was 6.24, equivalent to 16,021 people served by each contract dentist in 1939 (Showa 14). The chi-square test for the trend analysis of gender distribution indicated a significantly higher proportion of male than female contract dentists in either Taiwanese or Japanese ethnic group. Conclusion: In the late Japanese colonial period, the number of Taiwanese dentists exceeded that of Japanese dentists. Furthermore, there were more male than female dentists in either the Taiwanese or the Japanese population.

The mechanisms of Porphyromonas gingivalis-derived outer membrane vesicles-induced neurotoxicity and microglia activation.

Background/purpose: Periodontitis is associated with various systemic diseases, potentially facilitated by the passage of Porphyromonas gingivalis outer membrane vesicles (Pg-OMVs). Several recent studies have suggested a connection between Pg-OMVs and neuroinflammation and neurodegeneration, but the precise causal relationship remains unclear. This study aimed to investigate the mechanisms underlying these associations using in vitro models. Materials and methods: Isolated Pg-OMVs were characterized by morphology, size, and gingipain activity. We exposed SH-SY5Y neuroblastoma cells and BV-2 microglial cells to various concentrations of Pg-OMVs. Cell morphology, a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, an enzyme-linked immunosorbent assay, and Western blot analysis were used to evaluate the cellular mechanism underlying Pg-OMV-induced neurotoxicity in neuronal cells and inflammatory responses in microglial cells. Results: Exposure to Pg-OMVs induced neurotoxicity in SH-SY5Y cells, as evidenced by cellular shrinkage, reduced viability, activation of apoptotic pathways, and diminished neuronal differentiation markers. Gingipain inhibition mitigated these effects, suggesting that gingipain mediates Pg-OMVs-induced neurotoxicity in SH-SY5Y cells. Our research on neuroinflammation suggests that upon endocytosis of Pg-OMVs by BV-2 cells, lipopolysaccharide (LPS) can modulate the production of inducible nitric oxide synthase and tumor necrosis factor-alpha by activating pathways that involve phosphorylated AKT and the phosphorylated JNK pathway. Conclusion: Our study demonstrated that following the endocytosis of Pg-OMVs, gingipain can induce neurotoxicity in SH-SY5Y cells. Furthermore, the Pg-OMVs-associated LPS can trigger neuroinflammation via AKT and JNK signaling pathways in BV-2 cells.

Insights Into Colorectal Cancer Screening: A Multidatabase Cohort Study of Over 1.5 Million Taiwanese.

INTRODUCTION: Colorectal cancer (CRC) remains a significant public health concern. This study aims to provide a comprehensive understanding of the effectiveness of fecal immunochemical test (FIT) screening on CRC incidence and mortality, leveraging the scale of over 1.5 million randomly selected Taiwanese and more than 11.7 million person-years of follow-up. METHODS: This prospective cohort study merges data from 3 robust Taiwanese health databases: the CRC screening program, cancer registration, and death registration databases. Incidence and mortality rates of CRC were calculated based on age, sex, urbanization, and past screening status. Cox proportional hazard models were used to assess the association between screening statuses and CRC incidence or mortality, adjusting for age, sex, and urbanization levels. Statistical analysis of the data was conducted in 2021-2022. RESULTS: FIT screening was associated with a 33% reduction in CRC incidence and a 47% reduction in mortality. The study identified a dose-response relationship between the fecal hemoglobin concentration (f-HbC) levels and CRC risk. Participants with consistent FIT-negative results had significantly reduced CRC incidence and mortality risks, while those with one or more positive FIT results faced increased risks. Notably, compliance with follow-up examinations after a positive FIT significantly lowered mortality risk. CONCLUSIONS: This large-scale study validates the efficacy of FIT screening in reducing CRC incidence and mortality. It offers a nuanced understanding of how various screening statuses impact CRC risks, thus providing valuable insights for public health strategies aimed at CRC prevention.

N, N-Dimethyltryptamine, a natural hallucinogen, ameliorates Alzheimer's disease by restoring neuronal Sigma-1 receptor-mediated endoplasmic reticulum-mitochondria crosstalk.

BACKGROUND: Aberrant neuronal Sigma-1 receptor (Sig-1r)-mediated endoplasmic reticulum (ER)- mitochondria signaling plays a key role in the neuronal cytopathology of Alzheimer's disease (AD). The natural psychedelic N, N-dimethyltryptamine (DMT) is a Sig-1r agonist that may have the anti-AD potential through protecting neuronal ER-mitochondrial interplay. METHODS: 3×TG-AD transgenic mice were administered with chronic DMT (2 mg/kg) for 3 weeks and then performed water maze test. The Aß accumulation in the mice brain were determined. The Sig-1r level upon DMT treatment was tested. The effect of DMT on the ER-mitochondrial contacts site and multiple mitochondria-associated membrane (MAM)-associated proteins were examined. The effect of DMT on calcium transport between ER and mitochondria and the mitochondrial function were also evaluated. RESULTS: chronic DMT (2 mg/kg) markedly alleviated cognitive impairment of 3×TG-AD mice. In parallel, it largely diminished Aß accumulation in the hippocampus and prefrontal cortex. DMT restored the decreased Sig-1r levels of 3×TG-AD transgenic mice. The hallucinogen reinstated the expression of multiple MAM-associated proteins in the brain of 3×TG-AD mice. DMT also prevented physical contact and calcium dynamic between the two organelles in in vitro and in vivo pathological circumstances. DMT modulated oxidative phosphorylation (OXPHOS) and ATP synthase in the in vitro model of AD. CONCLUSION: The anti-AD effects of DMT are associated with its protection of neuronal ER-mitochondria crosstalk via the activation of Sig-1r. DMT has the potential to serve as a novel preventive and therapeutic agent against AD.