Summary
Epidemiologic evidence has shown inconsistent findings regarding the relationships between abdominal fatness, as measured by waist circumferences (WC) or waist‐to‐hip ratio (WHR), and risks ...of pre‐ and postmenopausal breast cancer (BC). A dose–response meta‐analysis of prospective studies was conducted to address these issues. Potentially eligible studies were identified by searching PubMed and EMBASE databases, and by carefully reviewing the bibliographies of retrieved publications and related reviews. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random‐effects model. When the most fully adjusted RRs were combined, both WC (14 studies, RR per 10‐cm increase = 1.06, 95% CI: 1.04–1.09, I2 = 29.9%) and WHR (15 studies, RR per 0.1‐unit increase = 1.07, 95% CI: 1.01–1.14, I2 = 52.9%) were significantly positively associated with postmenopausal BC, but neither WC (eight studies, RR per 10‐cm increase = 1.05, 95% CI: 0.99–1.10, I2 = 0%) nor WHR (11 studies, RR per 0.1‐unit increase = 1.07, 95% CI: 0.95–1.21, I2 = 59.7%) were associated with premenopausal BC. The WHR‐postmenopausal BC association lost statistical significance after correcting publication bias (RR per 0.1‐unit increase = 1.06, 95% CI: 0.99–1.13). When considering BMI‐adjusted RRs, WC was associated with both pre‐ (five studies, RR per 10‐cm increase = 1.09, 95% CI: 1.02–1.16, I2 = 0%) and postmenopausal BC (seven studies, RR per 10‐cm increase = 1.05, 95% CI: 1.02–1.08, I2 = 6.3%), whereas WHR was not associated with either pre‐ (seven studies, RR per 0.1‐unit increase = 1.12, 95% CI: 0.94–1.34, I2 = 70.9%) or postmenopausal BC (eight studies, RR per 0.1‐unit increase = 1.05, 95% CI: 0.98–1.13, I2 = 57.3%). Among non‐current (former or never) users of hormone replacement therapy, the summary RR per 10‐cm increase of postmenopausal BC associated with WC was 1.08 (95% CI: 1.03–1.05, I2 = 69.2%, seven studies; BMI‐adjusted RR = 1.05, 95% CI: 1.02–1.09, I2 = 22.8%, four studies). This meta‐analysis indicates that central obesity measured by WC, but not by WHR, is associated with modestly increased risks of both pre‐ and postmenopausal BC independent of general obesity.
Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment ...remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.
In this randomized trial involving infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth than was fresh-embryo transfer after the ...first transfer.
In vitro fertilization (IVF) is widely performed as an infertility treatment and has resulted in the births of more than 5 million infants worldwide.
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However, there are concerns about the safety of the procedures for women and for their infants.
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The ovarian hyperstimulation syndrome (which is caused by ovarian enlargement, an increase in vascular permeability and abdominal ascites, and intravascular hemoconcentration) is a potentially life-threatening complication of ovarian stimulation.
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Pregnancies conceived by means of IVF are associated with greater risks of maternal and neonatal complications, including preeclampsia, preterm delivery, low birth weight, and congenital anomalies, than are spontaneous pregnancies. . . .
Cancer genomic, transcriptomic, and proteomic profiling has generated extensive data that necessitate the development of tools for its analysis and dissemination. We developed UALCAN to provide a ...portal for easy exploring, analyzing, and visualizing these data, allowing users to integrate the data to better understand the gene, proteins, and pathways perturbed in cancer and make discoveries. UALCAN web portal enables analyzing and delivering cancer transcriptome, proteomics, and patient survival data to the cancer research community. With data obtained from The Cancer Genome Atlas (TCGA) project, UALCAN has enabled users to evaluate protein-coding gene expression and its impact on patient survival across 33 types of cancers. The web portal has been used extensively since its release and received immense popularity, underlined by its usage from cancer researchers in more than 100 countries. The present manuscript highlights the task we have undertaken and updates that we have made to UALCAN since its release in 2017. Extensive user feedback motivated us to expand the resource by including data on a) microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and promoter DNA methylation from TCGA and b) mass spectrometry-based proteomics from the Clinical Proteomic Tumor Analysis Consortium (CPTAC). UALCAN provides easy access to pre-computed, tumor subgroup-based gene/protein expression, promoter DNA methylation status, and Kaplan-Meier survival analyses. It also provides new visualization features to comprehend and integrate observations and aids in generating hypotheses for testing. UALCAN is accessible at http://ualcan.path.uab.edu
By designing a structured gas density profile between the dual-stage gas jets to manipulate electron seeding and energy chirp reversal for compressing the energy spread, we have experimentally ...produced high-brightness high-energy electron beams from a cascaded laser wakefield accelerator with peak energies in the range of 200-600 MeV, 0.4%-1.2% rms energy spread, 10-80 pC charge, and ∼0.2 mrad rms divergence. The maximum six-dimensional brightness B_{6D,n} is estimated as ∼6.5×10^{15} A/m^{2}/0.1%, which is very close to the typical brightness of e beams from state-of-the-art linac drivers. These high-brightness high-energy e beams may lead to the realization of compact monoenergetic gamma-ray and intense coherent x-ray radiation sources.
This paper presents a variant of particle swarm optimizers (PSOs) that we call the comprehensive learning particle swarm optimizer (CLPSO), which uses a novel learning strategy whereby all other ...particles' historical best information is used to update a particle's velocity. This strategy enables the diversity of the swarm to be preserved to discourage premature convergence. Experiments were conducted (using codes available from http://www.ntu.edu.sg/home/epnsugan) on multimodal test functions such as Rosenbrock, Griewank, Rastrigin, Ackley, and Schwefel and composition functions both with and without coordinate rotation. The results demonstrate good performance of the CLPSO in solving multimodal problems when compared with eight other recent variants of the PSO.
An effective tumor vaccine vector that can rapidly display neoantigens is urgently needed. Outer membrane vesicles (OMVs) can strongly activate the innate immune system and are qualified as ...immunoadjuvants. Here, we describe a versatile OMV-based vaccine platform to elicit a specific anti-tumor immune response via specifically presenting antigens onto OMV surface. We first display tumor antigens on the OMVs surface by fusing with ClyA protein, and then simplify the antigen display process by employing a Plug-and-Display system comprising the tag/catcher protein pairs. OMVs decorated with different protein catchers can simultaneously display multiple, distinct tumor antigens to elicit a synergistic antitumour immune response. In addition, the bioengineered OMVs loaded with different tumor antigens can abrogate lung melanoma metastasis and inhibit subcutaneous colorectal cancer growth. The ability of the bioengineered OMV-based platform to rapidly and simultaneously display antigens may facilitate the development of these agents for personalized tumour vaccines.
Abstract The magnetospheric cusp connects the planetary magnetic field to interplanetary space, offering opportunities for charged particles to precipitate to or escape from the planet. Terrestrial ...cusps are typically found near noon local time, but the characteristics of the Jovian cusp are unknown. Here we show direct evidence of Jovian cusps using datasets from multiple instruments onboard Juno spacecraft. We find that the cusps of Jupiter are in the dusk sector, which is contradicting Earth-based predictions of a near-noon location. Nevertheless, the characteristics of charged particles in the Jovian cusps resemble terrestrial and Saturnian cusps, implying similar cusp microphysics exist across different planets. These results demonstrate that while the basic physical processes may operate similarly to those at Earth, Jupiter’s rapid rotation and its location in the heliosphere can dramatically change the configuration of the cusp. This work provides useful insights into the fundamental consequences of star-planet interactions, highlighting how planetary environments and rotational dynamics influence magnetospheric structures.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been established as an effective treatment for patients with hematological malignancies. Disease relapse remains a major cause of ...transplant failure. T cell homeostasis is critical to determine the potency of the GVT effect. Recent studies have shown the association of the CTLA-4 polymorphisms with the outcome after HLA-identical sibling allogeneic HSCT.
In this study, we focused on four CTLA-4 polymorphisms, and analyzed the impact of donor genotypes and haplotypes on the conditions of 152 acute leukemia patients (ALL 83) after related HLA-haplotype- mismatched transplantation. The four SNP genotypes (-1661, -318, CT60 and +49) were determined by TaqMan SNP genotyping assays.
ALL recipients of donors with +49 GG showed significantly lower OS (67.7 vs. 90.3 %, P = 0.015) than those with GA+AA. Multivariate analyses showed that +49 GG was an independent risk factor for OS (HR: 0.306, 95 % CI 0.111-0.842, P = 0.022) .23 ALL patients receiving mDLI showed significantly lower OS with +49 GG donor than those with GA+AA (30.0 vs. 83.1 %, P = 0.003). The haplotype analysis revealed only three haplotypes in the donor population -1661/-318/CT60/+49 i.e., ACGG, ACAA and GTGA, the frequencies were 64.1, 19.4 and 16.5 %, respectively. Donors with and without the ACGG/ACGG haplotype had the same effect on transplant outcomes as those with +49 GG and +49 GA+AA.
In summary, the CTLA-4 +49 GG and the haplotype ACGG/ACGG reduced the overall survival in ALL after allo-HSCT from the related HLA-haplotype-mismatched donor, knowledge of the CTLA-4 polymorphism and haplotype may provide useful information for donor selection and individual application of immunosuppressive agents and immunotherapy.
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