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We investigated the copy number variation (CNV) of PDGFRA pathway across all common cancer types as well as its clinical relevance. This study included a total of 10,678 patients with pan-cancerous species involving 33 types of cancers and patient information was obtained from The Cancer Genome Atlas. According to the PDGFRA pathway CNV, all samples were divided into copy number gain (CN gain) group and No CN gain group. The analysis of loss of heterozygosity (LOH) fraction, CNV burden, tumor mutation burden (TMB), and the number of immunogenic mutations were performed, as well as the correlation analysis of PDGFRA pathway CN gain with tumor-related signaling pathways and tumor-infiltrating immune cell subpopulations. The results showed that CN gain of PDGFRA pathway in the cancer patients was associated with significantly shorter overall survival. The CN gain of PDGFRA pathway was identified as a prognostic risk factor for some tumors. CN gain was accompanied by an altered percentage of LOH, CNV burden, TMB, the number of immunogenic mutations were increased and tumor-infiltrating immune cell subpopulations were less. While certain tumor-related signaling pathways, such as hypoxia, cell cycle, DNA repair, and epithelial-mesenchymal transition were more enriched in the CN gain group, quiescence, and inflammation pathways were more enriched in the No CN gain group. In conclusion, PDGFRA pathway CNV gain may be a poor prognostic factor in cancer patients. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) immune checkpoint pathway has led to unprecedented advances in cancer therapy. However, the overall response rate of anti-PD-1/PD-L1 monotherapy is still unpromising, underscoring the need for predictive biomarkers. In this retrospective study, we collected pretreatment plasma samples from two independent cohorts of patients receiving ICB. To determine whether a signature of plasma cytokines could be associated with therapeutic efficacy, we systemically profiled cytokine clusters and functional groups in the discovery and validation datasets by using 59 multiplexed bead immunoassays and bioinformatics analysis. We first attempted to functionally classify the 59 immunological factors according to their biological classification or functional roles in the cancer-immunity cycle. Surprisingly, we observed that two signatures, the "checkpoint signature" and "trafficking of T-cell signature", were higher in the response subgroup than in the nonresponse subgroup in both the discovery and validation cohorts. Moreover, enrichment of the "checkpoint signature" was correlated with improved overall survival and progression-free survival in both datasets. In addition, we demonstrated that increased baseline levels of three checkpoint molecules (PD-L1, T-cell immunoglobulin mucin receptor 3 and T-cell-specific surface glycoprotein CD28) were common peripheral responsive correlates in both cohorts, thus rendering this "refined checkpoint signature" an ideal candidate for future verification. In the peripheral blood system, the "refined checkpoint signature" may function as a potential biomarker for anti-PD-1/PD-L1 monotherapy in gastrointestinal (GI) cancers. [ABSTRACT FROM AUTHOR]

This study explores change of precipitation and temperature using the Mann-Kendall test and the spatiotemporal variation of dryness/wetness using the standardized precipitation evapotranspiration index and empirical orthogonal function (EOF) analysis on 1-month time scales in Zhejiang Province, China, over 1971-2015. The results show that monthly precipitation had significant decreasing trends during April, May, September, and October, and significant increasing trends during November and December. Monthly temperatures had significant increasing trends in each month. Increasing temperature significantly increased drought events and intensity. There were consistent spatial patterns of dryness/wetness in Zhejiang. There were dryness trends in April, May, and September, a wetness trend in August, and no dryness/wetness pattern change in other months. The second EOF modes showed that dryness/wetness patterns were anti-phase between northern and southern Zhejiang during April-October. The third EOF modes showed that patterns were anti-phase between eastern and western Zhejiang in August and September. [ABSTRACT FROM AUTHOR]

Purpose: To describe the clinical and sonographic features of ovarian benign Brenner tumor (BBT) and malignant Brenner tumor (MBT), and to compare performance of four diagnostic models in differentiating them. Methods: Fifteen patients with BBTs and nine patients with MBTs were retrospectively identified in our institution from January 2003 and December 2021. One ultrasound examiner categorized each mass according to ovarian-adnexal reporting and data system (O-RADS), international ovarian tumor analysis (IOTA) Simple Rules Risk (SR-Risk) assessment and assessment of different neoplasias in the adnexa (ADNEX) models with/without CA125. Receiver operating characteristic curves were generated to compare diagnostic performance. Results: Patients with MBT had higher CA125 serum level (62.5% vs. 6.7%, P = 0.009) and larger maximum diameter of lesion (89 mm vs. 43 mm, P = 0.009) than did those with BBT. BBT tended to have higher prevalence of calcifications (100% vs. 55.6%, P = 0.012) and acoustic shadowing (93.3% vs. 33.3%, P = 0.004), and lower color scores manifesting none or minimal flow (100.0% vs. 22.2%, P < 0.001). Areas under curves of O-RADS, IOTA SR-Risk and ADNEX models with/without CA125 were 0.896, 0.913, 0.892 and 0.896, respectively. There were no significant differences between them. Conclusion: BBTs are often small solid tumors with sparse color Doppler signals, which contain calcifications with posterior acoustic shadowing. The most common pattern of MBT is a large multilocular-solid or solid mass with irregular tumor borders, and most were moderately or richly vascularized at color Doppler. These four models have excellent performance in distinguishing them. [ABSTRACT FROM AUTHOR]

It was suggested that the embryo pooling was an alternative for patients with insufficient number of embryos for preimplantation genetic testing (PGT) in a single ovarian stimulation cycle. However, limited study noticed whether it is an efficient strategy to pool cleavage-stage embryos by vitrification. This study included 71 cycles with vitrified-warmed and fresh embryos simultaneously for PGT between May 2016 and May 2021. The embryos from the same patients were split into two groups based on the origin: warming group and fresh group. Embryo development, sequencing results, clinical and neonatal outcomes were compared. The results showed that the rate of high-quality embryos in the warming group was significantly higher than that in the fresh group (64.53% versus 52.61%, P = 0.011); however, the available blastocyst rate in this group was significantly lower than that in the fresh group (47.29% versus 57.83%, P = 0.026). There were 96 and 144 blastocysts that underwent trophectoderm (TE) biopsy in warming and fresh groups, respectively. The high-quality blastocyst rate was significantly lower in the warming group compared to the fresh group (57.29% versus 70.14%, P = 0.041). The rates of genetic transferable blastocyst were comparable between the two groups (P = 0.956). There were no statistical differences in terms of embryo implantation, clinical pregnancy, miscarriage rates, and neonatal outcomes between the two groups. In conclusion, this study demonstrated that the cleavage-stage embryo pooling strategy might be unfavorable for the maintenance of embryonic development potential. If not necessary, it is not recommended to pool cleavage-stage embryos for PGT. [ABSTRACT FROM AUTHOR]

Based on phenological and economic output models established and meteorological data from 1972 to 2013, changes in the phenology, frost risk, and economic output of the Longjing-43 tea tree in the Yuezhou Longjing tea production area of China were evaluated. As the local climate has changed, the beginning dates of tea bud and leaf plucking of this cultivar in all five counties studied has advanced significantly by −1.28 to −0.88 days/decade, with no significant change in the risk of frost. The main tea-producing stages in the tea production cycle include the plucking periods for superfine, grade 1, and grade 2 buds and leaves. Among the five bud and leaf grades, the economic output of the plucking periods for superfine and grade 1 decreased significantly, that for grade 2 showed no significant change, and those for grades 3 and 4 increased significantly. The economic output of large-area tea plantations employing an average of 45 workers per hectare and producing superfine to grade 2 buds and leaves were significantly reduced by 6,745-8,829 yuan/decade/ha, depending on the county. Those tea farmers who planted tea trees on their own small land holdings and produced superfine to grade 4 tea buds and leaves themselves experienced no significant decline in economic output. [ABSTRACT FROM AUTHOR]

Immunotherapy has emerged as an effective therapeutic strategy for various cancers, including colorectal cancer (CRC), but only a subset of MSI-H patients can benefit from such therapy. Patched1 (PTCH1) is a frequently altered gene in CRCs and its mutations contribute to unregulated Hedgehog (Hh) signaling. In the study, we evaluated the association of PTCH1 mutations with CRC immunity based on our single-center cohort and multiple cancer genomic datasets. Among 21 enrolled patients, six (28.6%) harbored a PTCH1 mutation based on WES analyses. In CRC patients, the PTCH1 mutation subgroup experienced a higher durable clinical benefit rate than the PTCH1 wild-type subgroup (100% vs. 40%, P = 0.017). In addition, patients with the PTCH1 mutation experienced greater progression-free survival (PFS, P = 0.037; HR, 0.208) and overall survival (OS, P = 0.045; HR, 0.185). A validation cohort from the MSKCC also confirmed the correlation between PTCH1 mutation and better prognosis (P = 0.022; HR, 0.290). Mechanically, diverse antitumor immune signatures were more highly enriched in PTCH1-mutated tumors than in PTCH1 wild-type tumors. Furthermore, PTCH1-mutated tumors had higher proportions of CD8 + T cells, activated NK cells, and M1 type macrophage infiltration, as well as elevated gene signatures of several steps in the cancer-immunity cycle. Notably, the PTCH1 mutation was correlated with tumor mutational burden (TMB), loss of heterozygosity score, and copy number variation burden. Our results show that the mutation of PTCH1 is a potential biomarker for predicting the response of CRC patients to immunotherapy. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to analyze the impact of different biopsy protocols on the rate of mosaic blastocysts. Methods: This is a retrospective cohort study which included 115 cycles with pre-implantation genetic testing for aneuploidy (PGT-A). Two groups were allocated based on the biopsy protocols: method 1 group, the zona pellucida (ZP) was drilled on day 3 embryos followed by trophectoderm (TE) biopsy; and method 2 group, the ZP was opened on day 5 or 6 blastocysts followed by TE biopsy. All biopsy samples were assessed using next-generation sequencing (NGS) at a single reference laboratory. The euploid, aneuploid, and mosaic blastocyst rates and clinical outcomes were compared. Results: The mosaicism rate in the method 1 group was 19.58%, significantly higher than the method 2 group (8.12%; P < 0.05). No statistically significant difference was observed in euploid, aneuploid blastocyst rates, and clinical pregnancy rates between the two groups. Logistic regression analysis indicated that the biopsy protocols were independently associated with the mosaicism rates among all the variables. Conclusions: The present study showed that different biopsy protocols may have an impact on the mosaic blastocyst rate. ZP opening on day 3 combined with TE biopsy might increase the incidence of mosaic blastocysts. [ABSTRACT FROM AUTHOR]

Objectives: To establish methodological criteria for the clinical application of E-cervix technology in non-pregnant women, evaluate cervical differences between non-pregnant CI patients and normal women, and explore the predictive value of E-cervix for CI in non-pregnant women.Methods: In all, 46 non-pregnant women with CI and 46 non-pregnant women with full-term pregnancy experience were included. Elastic parameters (HR, IOS, EOS, IOS/EOS, CL) of the cervix were measured by transvaginal examination with a mid-sagittal section as the ROI, followed by examination of the whole cervix. The pressure of the probe on the cervix was divided into three levels. The elastic data of three consecutive images were separately obtained by two doctors for three pressure levels. Image stability and the effects of pressure were evaluated and the repeatability of the measurements was tested. In the case and control groups, cervical elasticity images were selected by standardized operation methods. Differences in the parameters between the two groups were determined and the diagnostic efficiency of each parameter was analyzed.Results: The HR, IOS, and EOS showed significant differences when measured on different sequential images obtained by continuous mapping (p < 0.05). The elastic parameters obtained from the first and last two images were significantly different (p < 0.05) and there were no significant differences between the elastic parameters obtained from the last two images (p > 0.05). The HR, IOS, EOS, and IOS/EOS showed significant differences among the pressure levels (p < 0.05), while the IOS showed a significant difference only between grades 0 and 2 (p < 0.05). E-cervix showed good repeatability within and among operators. The elastic parameters obtained by E-cervix in the CI group and control group were significantly different. ROC curve analysis showed that the HR was the most sensitive index for diagnosing CI.Conclusion: In E-cervix data acquisition, the first image should be excluded and the probe should not put pressure on the cervix. E-cervix has good retest and inter-observer reliability. Compared with normal women, CI patients showed a relatively softer and shorter cervix. E-cervix can be used as an important diagnostic tool for assessing cervical strain. [ABSTRACT FROM AUTHOR]