OBJECTIVE: To conduct a meta-analysis of studies assessing the effect of IVF and intracytoplasmic sperm injection (ICSI) on birth defects. DESIGN: Meta-analysis. SETTING: Centers for reproductive ...care. PATIENT(S): Patients treated by IVF and/or ICSI. INTERVENTION(S): We identified all studies published by September 2011 with data related to birth defects in children conceived by IVF and/or ICSI compared with spontaneously conceived children, or birth defects in the children conceived by IVF compared with those by ICSI. Risk ratios from individual studies were pooled with the fixed and random effect models. MAIN OUTCOME MEASURE(S): Risk of birth defects in children conceived by IVF and/or ICSI. RESULT(S): Of 925 studies reviewed for eligibility, 802 were excluded after screening titles and abstracts, 67 were excluded for duplicated data, data unavailable, or inappropriate control group, 56 were included in the final analysis. Among the 56 studies, 46 studies had data on birth defects in children conceived by IVF and/or ICSI (124,468) compared with spontaneously conceived children. These studies provided a pooled risk estimation of 1.37 (95% confidence interval CI: 1.26–1.48), which is also evident in subgroup analysis. In addition, 24 studies had data on birth defects in children conceived by IVF (46,890) compared with those by ICSI (27,754), which provided an overall no risk difference. CONCLUSION(S): Children conceived by IVF and/or ICSI are at significantly increased risk for birth defects, and there is no risk difference between children conceived by IVF and/or ICSI.
Inclusive tourism is a key part of an increasingly sustainable tourism development and harmony society. However, the degree, characteristics, and shortcomings of regional inclusive tourism ...development remain understudied. To holistically understand and describe the development of inclusive tourism in China, we develop an assessment model for inclusive tourism development from three dimensions: tourism stakeholders, economic inclusion, and tourism resources and environments. The spatial pattern and characteristics of China’s provincial inclusive tourism development is measured and classified. Furthermore, we conduct an in-depth discussion combined with specific indicators and propose the targeted suggestions. This study provides a basis for optimizing policies and practices of inclusive tourism in China. In addition, this study also contributes to the global body of knowledge surrounding inclusive tourism and provides the referee value for other countries.
The early detection of hepatocellular carcinoma (HCC) presents a challenge because of the lack of specific biomarkers. Serum/plasma microRNAs (miRNAs) can discriminate HCC patients from controls. We ...aimed to identify and evaluate HCC‐associated plasma miRNAs originating from the liver as early biomarkers for detecting HCC. In this multicenter three‐phase study, we first performed screening using both plasma (HCC before and after liver transplantation or liver hepatectomy) and tissue samples (HCC, para‐carcinoma and cirrhotic tissues). Then, we evaluated the diagnostic potential of the miRNAs in two case–control studies (training and validation sets). Finally, we used two prospective cohorts to test the potential of the identified miRNAs for the early detection of HCC. During the screening phase, we identified ten miRNAs, eight of which (miR‐20a‐5p, miR‐25‐3p, miR‐30a‐5p, miR‐92a‐3p, miR‐132‐3p, miR‐185‐5p, miR‐320a and miR‐324‐3p) were significantly overexpressed in the HBV‐positive HCC patients compared with the HBV‐positive cancer‐free controls in both the training and validation sets, with a sensitivity of 0.866 and specificity of 0.646. Furthermore, we assessed the potential for early HCC detection of these eight newly identified miRNAs and three previously reported miRNAs (miR‐192‐5p, miR‐21‐5p and miR‐375) in two prospective cohorts. Our meta‐analysis revealed that four miRNAs (miR‐20a‐5p, miR‐320a, miR‐324‐3p and miR‐375) could be used as preclinical biomarkers (pmeta < 0.05) for HCC. The expression profile of the eight‐miRNA panel can be used to discriminate HCC patients from cancer‐free controls, and the four‐miRNA panel (alone or combined with AFP) could be a blood‐based early detection biomarker for HCC screening.
What's new?
Half of all deaths from hepatocellular carcinoma (HCC) occur in China. But while early detection of the disease could improve survival, preclinical diagnostic biomarkers are lacking. Using tissue and plasma samples from HCC patients and plasma samples from prospective cohorts, the authors of this study evaluated the diagnostic and predictive potential of miRNAs. A panel of eight miRNAs dysregulated during HCC development successfully distinguished HCC patients from controls, while a panel of four miRNAs was found to have preclinical potential. The newly described miRNA panels could aid in the detection of HCC before the disease is otherwise clinically apparent.
Genetic variants and lifestyle factors have been associated with gastric cancer risk, but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unknown. We aimed ...to establish a genetic risk model for gastric cancer and assess the benefits of adhering to a healthy lifestyle in individuals with a high genetic risk.
In this meta-analysis and prospective cohort study, we first did a fixed-effects meta-analysis of the association between genetic variants and gastric cancer in six independent genome-wide association studies (GWAS) with a case-control study design. These GWAS comprised 21 168 Han Chinese individuals, of whom 10 254 had gastric cancer and 10 914 geographically matched controls did not. Using summary statistics from the meta-analysis, we constructed five polygenic risk scores in a range of thresholds (p=5 × 10−4 p=5 × 10−5 p=5 × 10−6 p=5 × 10−7, and p=5 × 10−8) for gastric cancer. We then applied these scores to an independent, prospective, nationwide cohort of 100 220 individuals from the China Kadoorie Biobank (CKB), with more than 10 years of follow-up. The relative and absolute risk of incident gastric cancer associated with healthy lifestyle factors (defined as not smoking, never consuming alcohol, the low consumption of preserved foods, and the frequent intake of fresh fruits and vegetables), was assessed and stratified by genetic risk (low quintile 1 of the polygenic risk score, intermediate quintile 2–4 of the polygenic risk score, and high quintile 5 of the polygenic risk score). Individuals with a favourable lifestyle were considered as those who adopted all four healthy lifestyle factors, those with an intermediate lifestyle adopted two or three factors, and those with an unfavourable lifestyle adopted none or one factor.
The polygenic risk score derived from 112 single-nucleotide polymorphisms (p<5 × 10−5) showed the strongest association with gastric cancer risk (p=7·56 × 10−10). When this polygenic risk score was applied to the CKB cohort, we found that there was a significant increase in the relative risk of incident gastric cancer across the quintiles of the polygenic risk score (ptrend<0·0001). Compared with individuals who had a low genetic risk, those with an intermediate genetic risk (hazard ratio HR 1·54 95% CI 1·22–1·94, p=2·67 × 10−4) and a high genetic risk (2·08 1·61–2·69, p<0·0001) had a greater risk of gastric cancer. A similar increase in the relative risk of incident gastric cancer was observed across the lifestyle categories (ptrend<0·0001), with a higher risk of gastric cancer in those with an unfavourable lifestyle than those with a favourable lifestyle (2·03 1·46–2·83, p<0·0001). Participants with a high genetic risk and a favourable lifestyle had a lower risk of gastric cancer than those with a high genetic risk and an unfavourable lifestyle (0·53 0·29–0·99, p=0·048), with an absolute risk reduction of 1·12% (95% CI 0·62–1·56).
Chinese individuals at an increased risk of incident gastric cancer could be identified by use of our newly developed polygenic risk score. Compared with individuals at a high genetic risk who adopt an unhealthy lifestyle, those who adopt a healthy lifestyle could substantially reduce their risk of incident gastric cancer.
National Key R&D Program of China, National Natural Science Foundation of China, 333 High-Level Talents Cultivation Project of Jiangsu Province, and China Postdoctoral Science Foundation.
Abstract In unraveling the profound connections between humans and place, the traditional concept of the sense of place takes on new dimensions in the digital era. This study contributes to a nuanced ...understanding by integrating digital and physical spaces within the context of information and communication technology (ICT). Beginning with a review of historical changes and debates surrounding the sense of place, the research establishes a foundation for understanding the evolving relationship with the place. Building on this, the study explores the intricate interplay between digital media and place, revealing how advancements in digital technology shape perceptions of the sense of place. Beyond analysis, the study introduces a three-dimensional framework for the sense of place (i.e., physical sense of place, digital sense of place, and hybrid sense of place), recognizing the dynamic relationship between individuals and their environment, incorporating the digital dimension. Firmly grounded in the perspective of relationships, this framework captures multifaceted connections individuals establish with both physical and digital spaces. Finally, the research explores practical applications of this reconceptualized sense of place. This research deepens the current understanding of the complex dynamics in constructing places in contemporary society, where digital and physical realms intertwine. This research serves as a crucial steppingstone for comprehending the evolving dynamics of the sense of place in the digital era, presenting a refined framework that captures the complex relationships between individuals, technology, and the places they inhabit.
Cancer-testis (CT) genes represent the similarity between the processes of spermatogenesis and tumorigenesis. It is possible that their selective expression pattern can help identify driver genes in ...cancer. In this study, we integrate transcriptomics data from multiple databases and systematically identify 876 new CT genes in 19 cancer types. We explore their relationship with testis-specific regulatory elements. We propose that extremely highly expressed CT genes (EECTGs) are potential drivers activated through epigenetic mechanisms. We find mutually exclusive associations between EECTGs and somatic mutations in mutated genes, such as PIK3CA in breast cancer. We also provide evidence that promoter demethylation and close non-coding RNAs (namely, CT-ncRNAs) may be two mechanisms to reactivate EECTG gene expression. We show that the meiosis-related EECTG (MEIOB) and its nearby CT-ncRNA have a role in tumorigenesis in lung adenocarcinoma. Our findings provide methods for identifying epigenetic-driver genes of cancer, which could serve as targets of future cancer therapies.
Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of ...site-specific and overall cancer.
Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs).
Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18-1.27) in men, and 1.26 (1.22-1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10-2.51) for men and 1.94 (1.78-2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = -1.01 in men, p<0.001; Beta = -0.98 in women, p<0.001).
Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle.
This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).
It has been demonstrated that there are abundant stable microRNAs (miRNAs) in plasma/serum, which can be detected and are potentially disease specific. However, the lack of suitable endogenous ...controls for serum miRNA detection is the restriction for the widely usage of this kind of biomarkers and for the between-laboratory comparison of the findings. We first systematically screened for endogenous control miRNAs (ECMs) by testing 10 pooling samples (using both Solexa sequencing and TaqMan low density array) and 50 individual samples (using quantitative reverse transcription-PCR) of different cancer traits and healthy controls. Then we assessed serum miRNAs used as potential biomarkers for breast cancer risk prediction based on a two-stage case-control analysis, including 48 breast cancer patients and 48 controls for the discovery stage and 76 breast cancer patients and 76 controls for validation. We identified two candidate ECMs (miRNA-191 and miRNA-484). Normalized by the two ECMs, we found four miRNAs (miR-16, miR-25, miR-222 and miR-324-3p) that were consistently differentially expressed between breast cancer cases and controls. The area under the receiver operating characteristic curve is 0.954 for the four-miRNA signature in the discovery stage (sensitivity = 0.917 and specificity = 0.896) and 0.928 in the validation stage (sensitivity = 0.921 and specificity = 0.934). In conclusion, the four-miRNA signature from serum may serve as a non-invasive prediction biomarker for breast cancer. Furthermore, we proposed the combination of miRNA-484 and miRNA-191 as endogenous control for serum miRNA detection, at least for most common cancers.
Gestational diabetes mellitus (GDM) is one type of diabetes that presents during pregnancy and significantly increases the risk of a number of adverse consequences for the fetus and mother. The ...microRNAs (miRNA) have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. However, no reported study investigates the associations between serum miRNA and GDM.
We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to screen miRNAs in serum collected at 16-19 gestational weeks. The expression levels of three miRNAs (miR-132, miR-29a and miR-222) were significantly decreased in GDM women with respect to the controls in similar gestational weeks in our discovery evaluation and internal validation, and two miRNAs (miR-29a and miR-222) were also consistently validated in two-centric external validation sample sets. In addition, the knockdown of miR-29a could increase Insulin-induced gene 1 (Insig1) expression level and subsequently the level of Phosphoenolpyruvate Carboxy Kinase2 (PCK2) in HepG2 cell lines.
Serum miRNAs are differentially expressed between GDM women and controls and could be candidate biomarkers for predicting GDM. The utility of miR-29a, miR-222 and miR-132 as serum-based non-invasive biomarkers warrants further evaluation and optimization.
Genetic variation has an important role in the development of non-small-cell lung cancer (NSCLC). However, genetic factors for lung cancer have not been fully identified, especially in Chinese ...populations, which limits the use of existing polygenic risk scores (PRS) to identify subpopulations at high risk of lung cancer for prevention. We therefore aimed to identify novel loci associated with NSCLC risk, and generate a PRS and evaluate its utility and effectiveness in the prediction of lung cancer risk in Chinese populations.
To systematically identify genetic variants for NSCLC risk, we newly genotyped 19 546 samples from Chinese NSCLC cases and controls from the Nanjing Medical University Global Screening Array Project and did a meta-analysis of genome-wide association studies (GWASs) of 27 120 individuals with NSCLC and 27 355 without NSCLC (13 327 cases and 13 328 controls of Chinese descent as well as 13 793 cases and 14 027 controls of European descent). We then built a PRS for Chinese populations from all reported single-nucleotide polymorphisms that have been reported to be associated with lung cancer risk at genome-wide significance level. We evaluated the utility and effectiveness of the generated PRS in predicting subpopulations at high-risk of lung cancer in an independent prospective cohort of 95 408 individuals from the China Kadoorie Biobank (CKB) with more than 10 years' follow-up.
We identified 19 susceptibility loci to be significantly associated with NSCLC risk at p≤5·0 × 10
, including six novel loci. When applied to the CKB cohort, the PRS of the risk loci successfully predicted lung cancer incident cases in a dose-response manner in participants at a high genetic risk (top 10%) than those at a low genetic risk (bottom 10%; adjusted hazard ratio 1·96, 95% CI 1·53-2·51; p
=2·02 × 10
). Specially, we observed consistently separated curves of lung cancer events in individuals at low, intermediate, and high genetic risk, respectively, and PRS was an independent effective risk stratification indicator beyond age and smoking pack-years.
We have shown for the first time that GWAS-derived PRS can be effectively used in discriminating subpopulations at high risk of lung cancer, who might benefit from a practically feasible PRS-based lung cancer screening programme for precision prevention in Chinese populations.
National Natural Science Foundation of China, the Priority Academic Program for the Development of Jiangsu Higher Education Institutions, National Key R&D Program of China, Science Foundation for Distinguished Young Scholars of Jiangsu, and China's Thousand Talents Program.
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