Autoimmune thyroiditis (AIT) is increasingly common, and serological markers include thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). To determine if selected metals influence ...thyroiditis antibody positivity, this cross-sectional study investigated associations between metals and thyroiditis antibody status. Healthy individuals (
n
= 1104) completed a questionnaire and underwent checkups of anthropometric parameters, thyroid function status, and levels of seven metals in blood (magnesium, iron, calcium, copper, zinc, manganese, and lead). Associated profiles of glyco- and lipid metabolism were also established. Logistic regression and restricted cubic spline (RCS) regression analysis were applied to adjudge associations between metals and TPOAb and TgAb status. It was found that, after adjusting for likely cofounding factors, participants with antibody positivity had significantly lower serum concentrations of magnesium and iron. When serum magnesium levels were analyzed in quartiles, the odds ratios of quartile 4 were 0.329–fold (95% confidence interval (CI): 0.167–0647) and 0.259-fold (95% CI 0.177–0.574) that of quartile 1 regarding TPOAb and TgAb positivity (
P
= 0.004, 0.003). After adjustment, the RCS analysis detected nonlinear associations between iron and TPOAb and TgAb positivity (
P
< 0.01, both). In stratified analyses, these associations regarding magnesium and iron remained for women of reproductive age, but not for postmenopausal women and men. We conclude that lower serum levels of magnesium and iron are associated with incremental positivity of thyroiditis antibodies and may be among the most important metals contributing to AIT in women of reproductive age.
Full text
Available for:
CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aims
Tumor electric fields therapy (TTFields) is emerging as a novel anti‐cancer physiotherapy. Despite recent breakthroughs of TTFields in glioma treatment, the average survival time for ...glioblastoma patients with TTFields is <2 years, even when used in conjugation with traditional anti‐cancer therapies. To optimize TTFields‐afforded efficacy against glioblastoma, we investigated the cancer cell‐killing effects of various TTFields paradigms using in vitro and in vivo models of glioblastoma.
Methods
For in vitro studies, the U251 glioma cell line or primary cell cultures prepared from 20 glioblastoma patients were treated with the tumor electric field treatment (TEFT) system. Cell number, volume, and proliferation were measured after TEFT at different frequencies (100, 150, 180, 200, or 220 kHz), durations (24, 48, or 72 h), field strengths (1.0, 1.5, or 2.2V/cm), and output modes (fixed or random sequence output). A transwell system was used to evaluate the influence of TEFT on the invasiveness of primary glioblastoma cells. For in vivo studies, the therapeutic effect and safety profiles of random sequence electric field therapy in glioblastoma‐transplanted rats were assessed by calculating tumor size and survival time and evaluating peripheral immunobiological and blood parameters, respectively.
Results
In the in vitro settings, TEFT was robustly effective in suppressing cell proliferation of both the U251 glioma cell line and primary glioblastoma cell cultures. The anti‐proliferation effects of TEFT were frequency‐ and “dose” (field strength and duration)‐dependent, and contingent on the field sequence output mode, with the random sequence mode (TEFT‐R) being more effective than the fixed sequence mode (TEFT‐F). Genetic tests were performed in 11 of 20 primary glioblastoma cultures, and 6 different genetic traits were identified them. However, TEFT exhibited comparable anti‐proliferation effects in all primary cultures regardless of their genetic traits. TEFT also inhibited the invasiveness of primary glioblastoma cells in transwell experiments. In the in vivo rat model of glioblastoma brain transplantation, treatment with TEFT‐F or TEFT‐R at frequency of 200 kHz and field strength of 2.2V/cm for 14 days significantly reduced tumor volume by 42.63% (TEFT‐F vs. control, p = 0.0002) and 63.60% (TEFT‐R vs. control, p < 0.0001), and prolonged animal survival time by 30.15% (TEFT‐F vs. control, p = 0.0415) and 69.85% (TEFT‐R vs. control, p = 0.0064), respectively. The tumor‐bearing rats appeared to be well tolerable to TEFT therapies, showing only moderate increases in blood levels of creatine and red blood cells. Adverse skin reactions were common for TEFT‐treated rats; however, skin reactions were curable by local treatment.
Conclusion
Tumor electric field treatment at optimal frequency, strength, and output mode markedly inhibits the cell viability, proliferation, and invasiveness of primary glioblastoma cells in vitro independent of different genetic traits of the cells. Moreover, a random sequence electric field output confers considerable anti‐cancer effects against glioblastoma in vivo. Thus, TTFields are a promising physiotherapy for glioblastoma and warrants further investigation.
Primary tumor cells prepared from 20 patients were treated with the tumor electric field treatment system (TEFTS). The impact of genetic background on cell responses to TEFTS were evaluated. Cell volume, cell number and cell proliferation were measured after TEFT at different frequencies (100, 150, 180, 200, 220 kHz). A transwell system was used to evaluate the influence of TEFT on the invasiveness of primary cells. The therapeutic effect and safety of random sequence electric field therapy in tumor‐bearing rats were assessed by calculating tumor size and survival time and by evaluating other immunobiological and blood parameters. Twelve types of primary tumor cells with different genetic traits were all sensitive to electric field treatment. After sensitive frequency treatment, the volume of primary cells significantly increased compared to control group, while the proliferation and invasiveness of tumor cells were inhibited. The optimal frequencies among all 20 types of primary cells were divided into different categories: 30% of them had the optimal frequency of 180 kHz; 25% of them had the optimal frequency of 200 kHz; 15% of them had the optimal frequency of 150 kHz, and 30% of them had the optimal frequency of 220 kHz. Two cases were not sensitive to 200 kHz. The therapy with random sequence electric field output significantly reduced tumor size and elongated survival time of tumor‐bearing rats compared to the fixed sequence TEFT, while increased the incidence of dermatological side effects.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background and objective
Nationally representative reports on the characteristics and long‐term survival of pulmonary arterial hypertension (PAH) from developing countries are scarce. The ...applicability of the current main risk stratifications and the longitudinal changes in goal‐oriented treatments have yet to be elucidated in real‐world settings. Therefore, we aimed to provide insights into the characteristics, goal‐oriented treatments and survival of PAH in China and to explore the applicability of the main risk stratifications in our independent cohort.
Methods
PAH patients were consecutively enrolled from a national prospective multicentre registry. Data on baseline, follow‐up re‐evaluation and therapeutic changes were collected.
Results
A total of 2031 patients were enrolled, with congenital heart disease (CHD)‐PAH (45.2%) being the most common aetiology. The mean age was 35 ± 12 years, and 76.2% were females. At baseline, approximately 20% of the patients with intermediate or high risk received combination treatment. At follow‐up, approximately half of the re‐evaluated patients did not achieve low‐risk profiles, and even among patients who received combination therapy at baseline, 4% of them still worsened. The rate of combination therapy increased significantly from 6.7% before 2015 to 35.5% thereafter. The main risk assessment tools demonstrated good performance for predicting survival both at baseline and at follow‐up.
Conclusion
Chinese PAH patients show both similar and distinct features compared to other countries. Current main risk stratifications can significantly discriminate patients at different risk levels. There were still many patients not achieving low‐risk profiles at follow‐up, indicating more aggressive treatment should be implemented to optimize the goal‐oriented treatment strategy.
This Chinese registry study revealed that Chinese patients with pulmonary arterial hypertension showed both similar and distinct features compared to other countries. Many patients did not achieve low‐risk profiles at follow‐up, indicating more aggressive treatment should be implemented to optimize goal‐oriented therapy for these patients.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This review explores the concept of life-on-a-chip, which involves the creation of miniaturized biological systems, such as organs, tissues, and model organisms, on microscale platforms called ...microfluidic chips. These chips consist of intricately etched channels, wells, and chambers that enable precise control and observation of fluids, cells, and biochemical reactions, facilitating the simulation of various aspects of human or animal physiology and the study of responses to different stimuli, drugs, or disease conditions. The review highlights the application of a novel technology, “Beyond Limit Manufacturing” (BLM), in the development of sophisticated three-dimensional cell models and model organism microchips. Model-organism-on-a-chip and organ-on-a-chip (OoC) are among the thriving developments in the field of microfluidics, allowing for the reconstruction of living microenvironments and implementation of multiple stimuli. The review discusses the latest advancements in life-on-a-chip technology using BLM and outlines potential future research directions, emphasizing the significant role of these chips in studying complex biological processes in a controlled and scalable manner.
This review explores the concept of life-on-a-chip, highlighting the utilization of "Beyond Limit Manufacturing" (BLM) technology to create advanced microchips, and discusses progress, potential, and future directions in this field.
Display omitted
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Most patients with cancer are refractory to immune checkpoint blockade (ICB) therapy, and proper patient stratification remains an open question. Primary patient data suffer from high heterogeneity, ...low accessibility, and lack of proper controls. In contrast, syngeneic mouse tumor models enable controlled experiments with ICB treatments. Using transcriptomic and experimental variables from >700 ICB-treated/control syngeneic mouse tumors, we developed a machine learning framework to model tumor immunity and identify factors influencing ICB response. Projected on human immunotherapy trial data, we found that the model can predict clinical ICB response. We further applied the model to predicting ICB-responsive/resistant cancer types in The Cancer Genome Atlas, which agreed well with existing clinical reports. Last, feature analysis implicated factors associated with ICB response. In summary, our computational framework based on mouse tumor data reliably stratified patients regarding ICB response, informed resistance mechanisms, and has the potential for wide applications in disease treatment studies.
Machine learning integrating mouse transcriptome and experimental variables predicts tumor immunity and immunotherapy response.
Abstract
In this paper, using the fluidity and parallelism of FPGA, we design a set of memory scheduling mechanism to implement an open convolutional neural network. The self-built vehicle database ...and the cropped and zoomed Daimler Pedestrian Detection Benchmark dataset are each trained under different network structures, and their recognition rates reached 97.8% and 98.6%. An open feedforward network is implemented on the FPGA platform, and experiments show that for small convolutional networks with different structures, the FPGA platform can increase its recognition speed when resources permit.
MHC-II is known to be mainly expressed on the surface of antigen-presenting cells. Evidence suggests MHC-II is also expressed by cancer cells and may be associated with better immunotherapy ...responses. However, the role and regulation of MHC-II in cancer cells remain unclear. In this study, we leveraged data mining and experimental validation to elucidate the regulation of MHC-II in cancer cells and its role in modulating the response to immunotherapy. We collated an extensive collection of omics data to examine cancer cell-intrinsic MHC-II expression and its association with immunotherapy outcomes. We then tested the functional relevance of cancer cell-intrinsic MHC-II expression using a syngeneic transplantation model. Finally, we performed data mining to identify pathways potentially involved in the regulation of MHC-II expression, and experimentally validated candidate regulators. Analyses of preimmunotherapy clinical samples in the CheckMate 064 trial revealed that cancer cell-intrinsic MHC-II protein was positively correlated with more favorable immunotherapy outcomes. Comprehensive meta-analyses of multiomics data from an exhaustive collection of data revealed that MHC-II is heterogeneously expressed in various solid tumors, and its expression is particularly high in melanoma. Using a syngeneic transplantation model, we further established that melanoma cells with high MHC-II responded better to anti-PD-1 treatment. Data mining followed by experimental validation revealed the Hippo signaling pathway as a potential regulator of melanoma MHC-II expression. In summary, we identified the Hippo signaling pathway as a novel regulator of cancer cell-intrinsic MHC-II expression. These findings suggest modulation of MHC-II in melanoma could potentially improve immunotherapy response.
Summary
Objective
Little is known about using glycated haemoglobin A1c (HbA1c) to diagnose diabetes in Chinese subjects over 50 years old. This study aims to evaluate HbA1c in diagnosing diabetes and ...identify the optimal threshold to be used in Chinese community subjects aged over 50 years.
Methods
A community‐based cross‐sectional survey was conducted from October 2010 to January 2011 in Shipai community of Guangzhou, Guangdong, China. A total of 1494 subjects (72·8%) aged over 50 years were investigated. Fasting plasma glucose (FPG1st) and HbA1c were assayed in each participant. Diabetic candidates with FPG1st ≥ 5·6 mmol/l or HbA1c ≥ 39 mmol/mol (5·7%) were informed to undergo a 75‐g oral glucose tolerance test (OGTT). Diagnosis of diabetes was made by 1999 World Health Organization criteria. Sensitivity and specificity of HbA1c for diagnosing diabetes were calculated by receiver operating characteristics (ROC) curve.
Results
Among 1494 subjects, 161 subjects (10·8%) with previously diagnosed diabetes and 21 with missing data were excluded. Among the remaining 1312 subjects (87·8%), 861 subjects (65·6%) with either FPG1st ≥ 5·6 mmol/l or HbA1c ≥ 39 mmol/mol (5·7%) were invited to perform OGTT. Finally, 453 subjects (52·6%) performed OGTT (FPG2nd and 2‐h plasma glucose were measured) and 54 subjects (11·9%) were identified as being diabetes. The area under ROC curve was 0·916 (0·887–0·940) for HbA1c and 0·972 (0·953–0·985) for FPG2nd in diagnosing diabetes (P = 0·045). An HbA1c threshold of 48 mmol/mol (6·5%) yielded the highest combination of sensitivity (75·9%) and specificity (95·5%) for diagnosing diabetes.
Conclusion
An HbA1c threshold of 48 mmol/mol (6·5%) was highly specific and had a good sensitivity for diagnosing diabetes among Chinese subjects aged over 50 years with FPG ≥ 5·6 mmol/l or HbA1c ≥ 39 mmol/mol (5·7%). This threshold may be suitable for diagnosing diabetes in Chinese subjects over 50 years old.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
PDF
