The number of people suffering from diabetes in Taiwan has continued to rise in recent years. According to the statistics of the International Diabetes Federation, about 537 million people worldwide ...(10.5% of the global population) suffer from diabetes, and it is estimated that 643 million people will develop the condition (11.3% of the total population) by 2030. If this trend continues, the number will jump to 783 million (12.2%) by 2045. At present, the number of people with diabetes in Taiwan has reached 2.18 million, with an average of one in ten people suffering from the disease. In addition, according to the Bureau of National Health Insurance in Taiwan, the prevalence rate of diabetes among adults in Taiwan has reached 5% and is increasing each year. Diabetes can cause acute and chronic complications that can be fatal. Meanwhile, chronic complications can result in a variety of disabilities or organ decline. If holistic treatments and preventions are not provided to diabetic patients, it will lead to the consumption of more medical resources and a rapid decline in the quality of life of society as a whole. In this study, based on the outpatient examination data of a Taipei Municipal medical center, 15,000 women aged between 20 and 80 were selected as the subjects. These women were patients who had gone to the medical center during 2018-2020 and 2021-2022 with or without the diagnosis of diabetes. This study investigated eight different characteristics of the subjects, including the number of pregnancies, plasma glucose level, diastolic blood pressure, sebum thickness, insulin level, body mass index, diabetes pedigree function, and age. After sorting out the complete data of the patients, this study used Microsoft Machine Learning Studio to train the models of various kinds of neural networks, and the prediction results were used to compare the predictive ability of the various parameters for diabetes. Finally, this study found that after comparing the models using two-class logistic regression as well as the two-class neural network, two-class decision jungle, or two-class boosted decision tree for prediction, the best model was the two-class boosted decision tree, as its area under the curve could reach a score of 0.991, which was better than other models.
Abstract
The escape of bladder cancer from immunosurveillance causes monotherapy to exhibit poor efficacy; therefore, designing a multifunctional nanoparticle that boosts programmed cell death and ...immunoactivation has potential as a treatment strategy. Herein, we developed a facile one-pot coprecipitation reaction to fabricate cluster-structured nanoparticles (CNPs) assembled from Fe
3
O
4
and iron chlorophyll (Chl/Fe) photosensitizers. This nanoassembled CNP, as a multifunctional theranostic agent, could perform red-NIR fluorescence and change the redox balance by the photoinduction of reactive oxygen species (ROS) and attenuate iron-mediated lipid peroxidation by the induction of a Fenton-like reaction. The intravesical instillation of Fe
3
O
4
@Chl/Fe CNPs modified with 4-carboxyphenylboronic acid (CPBA) may target the BC wall through glycoproteins in the BC cavity, allowing local killing of cancer cells by photodynamic therapy (PDT)-induced singlet oxygen and causing chemodynamic therapy (CDT)-mediated ferroptosis. An interesting possibility is reprogramming of the tumor microenvironment from immunosuppressive to immunostimulatory after PDT-CDT treatment, which was demonstrated by the reduction of PD-L1 (lower “off” signal to the effector immune cells), IDO-1, TGF-β, and M2-like macrophages and the induction of CD8
+
T cells on BC sections. Moreover, the intravesical instillation of Fe
3
O
4
@Chl/Fe CNPs may enhance the large-area distribution on the BC wall, improving antitumor efficacy and increasing survival rates from 0 to 91.7%. Our theranostic CNPs not only demonstrated combined PDT-CDT-induced cytotoxicity, ROS production, and ferroptosis to facilitate treatment efficacy but also opened up new horizons for eliminating the immunosuppressive effect by simultaneous PDT-CDT.
With the rising need for accessible cervical cancer screening, self‐sampling methods offer a promising alternative to traditional physician‐led sampling. This study aims to evaluate the efficacy of ...the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high‐risk HPV (hrHPV) types between samples collected by physicians and those self‐collected by women using a self‐sampling kit for validation. Women aged 21–65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician‐sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self‐sampling kit closely matched the physician‐led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval 95% CI: 0.72–0.79; agreement: 87.7%, 95% CI: 85.8–89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72–0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user‐friendly alternative to traditional sampling methods. This suggests that self‐sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.
MicroRNAs (miRNAs) are small noncoding RNAs that play fundamental roles in diverse biological and pathological processes by targeting the expression of specific genes. Here, we identified 38 ...methylation‐associated miRNAs, the expression of which could be epigenetically restored by cotreatment with 5‐aza‐2′‐deoxycytidine and trichostatin A. Among these 38 miRNAs, we further analyzed miR‐34b, miR‐127‐3p, miR‐129‐3p and miR‐409 because CpG islands are predicted adjacent to them. The methylation‐silenced expression of these miRNAs could be reactivated in gastric cancer cells by treatment with demethylating drugs in a time‐dependent manner. Analysis of the methylation status of these miRNAs showed that the upstream CpG‐rich regions of mir‐34b and mir‐129‐2 are frequently methylated in gastric cancer tissues compared to adjacent normal tissues, and their methylation status correlated inversely with their expression patterns. The expression of miR‐34b and miR‐129‐3p was downregulated by DNA hypermethylation in primary gastric cancers, and the low expression was associated with poor clinicopathological features. In summary, our study shows that tumor‐specific methylation silences miR‐34b and miR‐129 in gastric cancer cells.
Plasticizers/phthalates play a facilitating role in the development of cancer and help the tumor to grow and metastasize. Camptothecin (CPT) and its derivatives are known to have anticancer ...properties of inhibiting cell growth, promoting cell apoptosis, and increasing autophagy. Therefore, in this study, we investigated whether the presence of di(2‐ethylhexyl) phthalate (DEHP) could hinder apoptosis and autophagy caused by CPT in non‐small cell lung cancer (NSCLC) cells. We found that DEHP interferes with CPT‐induced apoptosis and autophagy and increases the prosurvival pathway by reducing the DNA damage marker γ‐H2AX and activating the Akt and NF‐κB pathways. Furthermore, we also confirmed that combining DEHP with 3‐MA has additive effects in inhibiting autophagy and apoptosis in NSCLC cells. Taken together, our findings show that DEHP could affect CPT‐induced anticancer treatment and provide evidence to show that DEHP induces chemoresistance in CPT‐based chemotherapy.
A high breakdown voltage of 11.7 V is achieved for a GeSn ultrathin (<inline-formula> <tex-math notation="LaTeX">\sim </tex-math></inline-formula>2 nm) body nanosheet p-channel field-effect ...transistor. This voltage is 5.7 V higher than that for a 10-nm GeSn nanosheet. The large effective bandgap associated with the quantum confinement in the <inline-formula> <tex-math notation="LaTeX">\sim </tex-math></inline-formula>2-nm Ge<inline-formula> <tex-math notation="LaTeX">_{{0}.{9}} </tex-math></inline-formula>Sn<inline-formula> <tex-math notation="LaTeX">_{{0}.{1}} </tex-math></inline-formula> channel is responsible for the enhanced breakdown voltage. An extremely scaled Ge<inline-formula> <tex-math notation="LaTeX">_{{0}.{9}} </tex-math></inline-formula>Sn<inline-formula> <tex-math notation="LaTeX">_{{0}.{1}} </tex-math></inline-formula> ultrathin body with channel thickness reduced to <inline-formula> <tex-math notation="LaTeX">\sim </tex-math></inline-formula>2 nm is realized through the co-optimization of low-temperature epitaxy and selective isotropic etching. As-grown Ge<inline-formula> <tex-math notation="LaTeX">_{{0}.{9}} </tex-math></inline-formula>Sn<inline-formula> <tex-math notation="LaTeX">_{{0}.{1}} </tex-math></inline-formula> channel layers as thin as 4 nm sandwiched by Ge<inline-formula> <tex-math notation="LaTeX">_{{0}.{97}} </tex-math></inline-formula>Sn<inline-formula> <tex-math notation="LaTeX">_{{0}.{03}} </tex-math></inline-formula>/Ge caps are carefully designed for ultrathin bodies. Radical-based highly selective isotropic dry etching is adopted to etch the caps and sacrificial layers and to release the GeSn ultrathin body channels. In addition, owing to strong quantum confinement in the <inline-formula> <tex-math notation="LaTeX">\sim </tex-math></inline-formula>2-nm ultrathin body, a high <inline-formula> <tex-math notation="LaTeX">{I}_{\text {ON}}/{I}_{\text {OFF}} </tex-math></inline-formula> ratio of <inline-formula> <tex-math notation="LaTeX">\ge 1.7 \times 10^{{7}} </tex-math></inline-formula> at <inline-formula> <tex-math notation="LaTeX">{V}_{\text {DS}} </tex-math></inline-formula> = -0.5 V is achieved.
We aimed to compare the efficacy of genotypic resistance–guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials.
We performed ...2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance–guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate.
H pylori infection was eradicated in 17 of 21 (81%) patients receiving genotype resistance–guided therapy and 12 of 20 (60%) patients receiving empirical therapy (P = .181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 57.7%). In trial 2, H pylori infection was eradicated in 160 of 205 (78%) patients receiving genotype resistance–guided therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P = .170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups.
Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance–guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.
Display omitted
Snail is primarily known as a transcriptional repressor that induces epithelial-mesenchymal transition by suppressing adherent proteins. Emerging evidence suggests that Snail can act as an activator; ...however, the mechanism and biological significance are unclear. Here, we found that CREB-binding protein (CBP) is the critical factor in Snail-mediated target gene transactivation. CBP interacts with Snail and acetylates Snail at lysine 146 and lysine 187, which prevents the repressor complex formation. We further identified several Snail-activated targets, including TNF-α, which is also the upstream signal for Snail acetylation, and CCL2 and CCL5, which promote the recruitment of tumor-associated macrophages. Here, we present our results on the mechanism by which Snail induces target gene transactivation to remodel the tumor microenvironment.
Display omitted
•TNF-α potentiates CBP-induced acetylation of Snail at lysine 146 and lysine 187•Acetylation of Snail prevents the formation of the Snail repressor complex•Acetylation of Snail induces transcription of TNFA, CCL2, and CCL5•Acetylation of Snail promotes the recruitment of tumor-associated macrophages
Hsu et al. report that Snail acetylation by CBP prevents repressor complex formation and allows target gene transactivation. Snail-mediated transactivation of TNFA provides the upstream signal for Snail acetylation, whereas that of CCL2 and CCL5 promotes tumor-associated macrophage recruitment.
Tissue stroma is known to be important in regulating Hp-mediated inflammation, but its interaction with Hp and dendritic cells (DCs) remains to be determined. To this end, the potential crosstalk ...between H. pylori (Hp) infected gastric stromal cells (Hp-GSCs) and DCs was investigated. Primary GSCs from cancerous and adjacent normal tissues were generated from gastric cancer patients, and monocyte-derived DCs were obtained from healthy individuals. Levels of cytokines and prostaglandin E
(PGE
) were measured by ELISA, and C-type lectin expression in GSCs was assessed by flow cytometry and immunohistochemistry. In a trans-well co-culture system, significantly upregulated DC-derived IL-23 expression was found when DCs were co-cultured with Hp-infected GSCs (Hp-GSCs). Further, PGE
from Hp-GSCs was discovered to possess the priming effect, which could be inhibited by anti-COLEC12 (Collectin subfamily member 12) Abs, COLEC12 knockdown or when alpha3-fucosyltransferase-null (futB; HP0651) strain of Hp was used. Also, the expression of COLEC12 was co-localized with CD90
stromal cells in cancerous tissues. Hp-GSCs-conditioned DCs were able to induce the expression of IL-17 from CD4
T cells, which could be inhibited by IL-23-neutralizing Abs. These results suggested the importance of COLEC12 as a receptor involved in Hp-stromal cell interaction and its subsequent conditioning effect on DCs.
PDF
