Nevin Manimala

Zhonghua Zhong Liu Za Zhi. 2023 Jan 23;45(1):56-63. doi: 10.3760/cma.j.cn112152-20200623-00588.

ABSTRACT

Objective: To investigate the effect of long non-coding RNA urothelial carcinoma-associated 1 (UCA1) gene on the proliferation, migration, apoptosis and immune escape of endometrial cancer cells and its molecular mechanism. Methods: Endometrial cancer tissues and adjacent normal tissues of patients with endometrioid adenocarcinoma who underwent total or partial hysterectomy in Henan Provincial People’s Hospital from 2017 to 2019 were collected. The expressions of UCA1 and miR-204-5p were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and the cell proliferation, migration and apoptosis were detected by cell counting kit 8 (CCK8) method, Transwell method, flow cytometry, and dual-luciferase reporter assay was used to explore the target relationship between UCA1 and miR-204-5p. HEC-1A-sh-NC or HEC-1A-sh-UCA1 cells were co-cultured with peripheral blood mononuclear cells (PBMC) or cytokine-induced killer cells in vitro to explore the role of UCA1 in immune escape. Results: The expression level of UCA1 in endometrial cancer tissue (17.08±0.84) was higher than that in adjacent normal endometrial tissue (3.00±0.37), and the expression level of miR-204-5p (0.98±0.16) was lower than that in adjacent normal endometrial tissue (2.00±0.20, P<0.05). Pearson correlation analysis showed that the expression of miR-204-5p was negatively correlated with the expression of UCA1 (r=-0.330, P=0.030). The expressions of UCA1 and miR-204-5p were associated with the International Federation of Gynecology and Obstetrics stage of endometrial cancer, lymph node metastasis and vascular invasion (P<0.05). The relative ratio of absorbance (0.58±0.11) and the number of cell migration [(199.68±18.44)] in the sh-UCA1 group were lower than those in the sh-NC group (1.24±0.17 and 374.76±24.83), respectively. The apoptosis rate of sh-UCA1 group [(28.64±7.80)%] was higher than that of sh-NC group [(14.27±4.38)%, P<0.05]. After different ratios of effector cells and target cells were cultured, the cell survival rate of HEC-1A-sh-UCA1 group was lower than that of HEC-1A-sh-NC group, and the difference was statistically significant (P<0.05). UCA1 had a binding site for miR-204-5p. The relative ratio of absorbance (1.74±0.08) and the number of cell migration (426.00±18.00) cells in the UCA1+ anti-miR-204-5p group were higher than those in the control group [1.00±0.03 and (284.00±8.00) cells, respectively]. The apoptosis rate of UCA1+ anti-miR-204-5p group [(5.42±0.93)%] was lower than that of control group [(14.82±1.48)%, P<0.05]. HEC-1A-sh-UCA1 cells could induce higher interferon gamma (IFN-γ) expression when co-cultured with PBMC, and the levels of IFN-γ expression in PHA group and PHA+ pre-miR-204-5p group cells were 2.42±0.49 and 1.88±0.26, which were higher than that in the PHA+ pre-NC group (0.85±0.10, P<0.05). When co-cultured with cytokine-induced killer cells (different ratios) in vitro, the HEC-1A-sh-UCA1 group and the HEC-1A-pre-miR-204-5p group had lower survival rates than that in the HEC-1A-pre-miR-204-5p group. In the HEC-1A-pre-NC group, the differences were statistically significant (P<0.05). Conclusion: UCA1/miR-204-5p may play an important role in human endometrial cancer.

PMID:36709121 | DOI:10.3760/cma.j.cn112152-20200623-00588

Zhonghua Xue Ye Xue Za Zhi. 2022 Dec 14;43(12):992-1002. doi: 10.3760/cma.j.issn.0253-2727.2022.12.004.

ABSTRACT

Objective: To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases. Methods: From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14-62) years, with 363 males (56.0% ) and 285 females (44.0% ) present. 242 cases of acute lymphoblastic leukemia (ALL) (37.3% ) , 293 cases of acute myeloid leukemia (AML) (45.2% ) , 56 cases of myelodysplastic syndrome (MDS) (8.7% ) , 27 cases of non-Hodgkin’s lymphoma (NHL) (4.2% ) , and 30 cases of other hematological malignancies (4.6% ) . Results: ① The 3-year overall survival (OS) , DFS, the incidence of Ⅱ-Ⅳ grade acute graft-versus-host disease (aGVHD) , the incidence of Ⅲ-Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD (cGVHD) , severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were (73.10±1.90) % , (70.80±1.90) % , (33.96±1.87) % , (13.08±1.33) % , (35.10±2.14) % , (10.66±1.38) % , (19.43±1.67) % , and (9.80±1.24) % , respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups (P=0.148) . The incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups (P>0.05) . The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group [ (91.45±2.63) % vs. (94.77±1.75) % , P=0.004; (91.45±2.63) % vs. (95.54±2.05) % , P=0.005]. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group [ (91.45±2.63) % vs. (95.08±1.41) % , P=0.284]. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were (26.71±5.90) % and (10.33±4.43) % , respectively (P=0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% vs. 27.41% , respectively, among those over 35 (40.07±6.65) % vs. (27.41±4.54) % (P=0.084) . ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups [ (91.45±2.63) % vs. (95.08±0.95) % , P=0.037]. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius (ATG-F) 10 mg/kg group [ (89.29±4.29) % vs. (94.49±1.45) % , P=0.037]. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin (rATG-T) 6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different [ (93.44±3.38) % vs. (95.62±1.26) % , P=0.404]. Conclusion: The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.

PMID:36709104 | DOI:10.3760/cma.j.issn.0253-2727.2022.12.004

J Pediatr Surg. 2023 Jan 3:S0022-3468(22)00834-X. doi: 10.1016/j.jpedsurg.2022.12.030. Online ahead of print.

ABSTRACT

BACKGROUND: The optimal timing of surgical repair for infants with congenital diaphragmatic hernia (CDH) treated with extracorporeal membrane oxygenation (ECMO) support remains controversial. The risk of surgical bleeding is considered by many centers as a primary factor in determining the preferred timing of CDH repair for infants requiring ECMO support. This study compares surgical bleeding following CDH repair on ECMO in early versus delayed fashion.

METHODS: A retrospective review of 146 infants who underwent CDH repair while on ECMO support from 1995 to 2021. Early repair occurred during the first 48 h after ECMO cannulation (ER) and delayed repair after 48 h (DR). Surgical bleeding was defined by the requirement of reoperative intervention for hemostasis or decompression.

RESULTS: 102 infants had ER and 44 infants DR. Surgical bleeding was more frequent in the DR group (36% vs 5%, p < 0.001) with an odds ratio of 11.7 (95% CI: 3.48-39.3, p < 0.001). Blood urea nitrogen level on the day of repair was significantly elevated among those who bled (median 63 mg/dL, IQR 20-85) vs. those who did not (median 9 mg/dL, IQR 7-13) (p < 0.0001). Duration of ECMO support was shorter in the ER group (median 13 vs 18 days, p = 0.005). Survival was not statistically different between the two groups (ER 60% vs. DR 57%, p = 0.737).

CONCLUSION: We demonstrate a significantly lower incidence of bleeding and shorter duration of ECMO with early CDH repair. Azotemia was a strong risk factor for surgical bleeding associated with delayed CDH repair on ECMO.

LEVEL OF EVIDENCE: Level III cohort study.

PMID:36709093 | DOI:10.1016/j.jpedsurg.2022.12.030

Sci Rep. 2023 Jan 27;13(1):1487. doi: 10.1038/s41598-023-27695-0.

ABSTRACT

Most of the studies about mental health and quality of life of emerging adults have been conducted in developed countries and non-students’ population has been neglected, limiting the generalisation of the results to other socioeconomic realities. This paper reports the results of an observational study on differences between the two cohorts (students vs non-students) both on mental health and quality of life measures but also on demographic, lifestyle and mental health variables in emerging adults living in a middle-income country. Associations between variables and interactions in the prediction of both outcomes scores were explored to understand how much other variables may contribute to differences between the two groups. We found poorer mental health and worse health-related quality of life in the students than the non-students, although effect sizes were small. Differences between the groups on some sociodemographic predictor variables were statistically significant, showing fairly strong effects, for social status, sleeping hours and parenting, however, none of the predictor variables showed confounding with group effects on both outcomes. Developing countries are growing and work forces are changing, creating a huge global need to understand these changes and the effects on the mental health and quality of life of this evolving population.Registration: ClinicalTrials.gov (NCT04596345).

PMID:36707675 | DOI:10.1038/s41598-023-27695-0

Sci Rep. 2023 Jan 27;13(1):1553. doi: 10.1038/s41598-023-28549-5.

ABSTRACT

Certain cut-off points for sarcopenia screening and diagnosis are arbitrary and based on European populations, with normative references often obtained from healthy young adults. Although respiratory skeletal muscle strength tests represent low-cost clinical measures commonly performed in clinical practice by health professionals, a gap remains regarding whether respiratory skeletal muscle strength tests are adequate and sensitive measures for sarcopenia screening. This study aimed to verify the value of handgrip and respiratory muscle strength as possible discriminators to identify sarcopenia and to establish cut-off points for sarcopenia screening in community-dwelling, Brazilian women. In a cross-sectional study, 154 community-dwelling, Brazilian women (65-96 years) were assessed for appendicular skeletal muscle mass, handgrip (HGS), and respiratory muscular strength, including maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). The data were analyzed using the ROC curve and the Youden Index determined cut-off points. Statistical significance was set at 5%. 88 participants (57%) were sarcopenic. MEP (OR 0.98 [95%CI 0.97, 1.00], p = 0.023) and HGS (OR 0.82 [95% CI 0.75, 0.90], p < 0.001) were independent factors for sarcopenia in older. The optimal cut-off points for identifying sarcopenia were ≤ 77 cmH₂O for MEP (AUC = 0.72), and ≤ 20 kg for HGS (AUC = 0.80). Simple muscular strength tests, including HGS and MEP, may be considered in the identification of sarcopenia in older, community-dwelling, Brazilian women. Future work is still needed to assess external validation of the proposed cut-offs before the clinical application.

PMID:36707661 | DOI:10.1038/s41598-023-28549-5

NPJ Precis Oncol. 2023 Jan 27;7(1):14. doi: 10.1038/s41698-023-00352-5.

ABSTRACT

Advances in computational algorithms and tools have made the prediction of cancer patient outcomes using computational pathology feasible. However, predicting clinical outcomes from pre-treatment histopathologic images remains a challenging task, limited by the poor understanding of tumor immune micro-environments. In this study, an automatic, accurate, comprehensive, interpretable, and reproducible whole slide image (WSI) feature extraction pipeline known as, IMage-based Pathological REgistration and Segmentation Statistics (IMPRESS), is described. We used both H&E and multiplex IHC (PD-L1, CD8+, and CD163+) images, investigated whether artificial intelligence (AI)-based algorithms using automatic feature extraction methods can predict neoadjuvant chemotherapy (NAC) outcomes in HER2-positive (HER2+) and triple-negative breast cancer (TNBC) patients. Features are derived from tumor immune micro-environment and clinical data and used to train machine learning models to accurately predict the response to NAC in breast cancer patients (HER2+ AUC = 0.8975; TNBC AUC = 0.7674). The results demonstrate that this method outperforms the results trained from features that were manually generated by pathologists. The developed image features and algorithms were further externally validated by independent cohorts, yielding encouraging results, especially for the HER2+ subtype.

PMID:36707660 | DOI:10.1038/s41698-023-00352-5

Pharm Stat. 2023 Jan 27. doi: 10.1002/pst.2290. Online ahead of print.

ABSTRACT

Here we present as case study how re-randomization tests were performed in two randomized, controlled clinical trials as sensitivity analyses, as recommended by the United States Food and Drug Administration in the context of adaptive randomization. This was done to confirm primary conclusions on immunological noninferiority of an investigational new fully liquid presentation of a quadrivalent cross-reacting material conjugate meningococcal vaccine (MenACWY-CRM), over its licensed lyophilized/liquid presentation. In two phase 2b studies (Study #1: NCT03652610; Study #2: NCT03433482), noninferiority of the fully liquid presentation of MenACWY-CRM to the licensed presentation was assessed and demonstrated for immune responses against meningococcal serogroup A (MenA), the only vaccine component modified from lyophilized to liquid in the new presentation. The original vaccine assignment algorithm, with a minimization procedure accounting for center or center within age strata, was used to re-randomize participants belonging to the fully liquid and licensed vaccine groups while keeping antibody responses, covariates and entry order as observed. Test statistics under re-randomization were generated according to the ANCOVA model used in the primary analysis. To confirm immunological noninferiority following re-randomization, the corresponding p-values had to be <0.025. For both studies and all primary objective evaluations, the re-randomization p-values were well below 0.025 (0.0004 for Study #1; 0.0001 for the two co-primary endpoints in Study #2). Re-randomization tests performed to comply with a regulatory request confirmed the primary conclusions of immunological noninferiority for the MenA of the fully liquid compared to the licensed vaccine presentation.

PMID:36707656 | DOI:10.1002/pst.2290

Nat Hum Behav. 2023 Jan;7(1):15-26. doi: 10.1038/s41562-022-01497-2. Epub 2023 Jan 26.

ABSTRACT

Flexibility in the design, analysis and interpretation of scientific studies creates a multiplicity of possible research outcomes. Scientists are granted considerable latitude to selectively use and report the hypotheses, variables and analyses that create the most positive, coherent and attractive story while suppressing those that are negative or inconvenient. This creates a risk of bias that can lead to scientists fooling themselves and fooling others. Preregistration involves declaring a research plan (for example, hypotheses, design and statistical analyses) in a public registry before the research outcomes are known. Preregistration (1) reduces the risk of bias by encouraging outcome-independent decision-making and (2) increases transparency, enabling others to assess the risk of bias and calibrate their confidence in research outcomes. In this Perspective, we briefly review the historical evolution of preregistration in medicine, psychology and other domains, clarify its pragmatic functions, discuss relevant meta-research, and provide recommendations for scientists and journal editors.

PMID:36707644 | DOI:10.1038/s41562-022-01497-2

Eur J Hum Genet. 2023 Jan 27. doi: 10.1038/s41431-022-01257-w. Online ahead of print.

ABSTRACT

Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCM MVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry. Sixteen common MVs were tested individually; the remaining rare 673 MVs were tested by burden analyses considering their position and pathogenicity score. We also conducted a meta-analysis of our results and those from published studies. We did not find evidence for association for any of the 16 variants individually tested. The rare MVs were significantly associated with increased risk of ER-negative breast cancer by burden analysis comparing familial cases to controls (OR = 1.48; 95% CI 1.07-2.04; P = 0.017). Higher ORs were found for the subgroup of MVs located in functional domains or predicted to be pathogenic. The meta-analysis indicated that FANCM MVs overall are associated with breast cancer risk (OR = 1.22; 95% CI 1.08-1.38; P = 0.002). Our results support the definition from previous analyses of FANCM as a moderate-risk breast cancer gene and provide evidence that FANCM MVs could be low/moderate risk factors for ER-negative and TNBC subtypes. Further genetic and functional analyses are necessary to clarify better the increased risks due to FANCM MVs.

PMID:36707629 | DOI:10.1038/s41431-022-01257-w

Sci Rep. 2023 Jan 27;13(1):1548. doi: 10.1038/s41598-023-28809-4.

NO ABSTRACT

PMID:36707616 | DOI:10.1038/s41598-023-28809-4