Nevin Manimala

J Ovarian Res. 2024 Oct 21;17(1):208. doi: 10.1186/s13048-024-01526-w.

ABSTRACT

BACKGROUND: Immunotherapy has revolutionized the treatment of ovarian cancer (OC), but different immune microenvironments often constrain the efficacy of immunotherapeutic interventions. Therefore, there is an imperative to delineate novel immune subtypes for development of efficacious immunotherapeutic strategies.

METHODS: The immune subtypes of OC were identified by consensus cluster analysis. The differences in clinical features, genetic mutations, mRNA stemness (mRNAsi) and immune microenvironments were analyzed among subtypes. Subsequently, prognostic risk models were constructed based on differentially expressed genes (DEGs) of the immune subtypes using weighted correlation network analysis.

RESULTS: OC patients were classified into three immune subtypes with distinct survival rates and clinical features. Different subtypes exhibited varying tumor mutation burdens, homologous recombination deficiencies, and mRNAsi levels. Significant differences were observed among immune subtypes in terms of immune checkpoint expression and immunogenic cell death. Prognostic risk models were validated as independent prognostic factors demonstrated great predictive performance for survival of OC patients.

CONCLUSION: In this study, three distinct immune subtypes were identified based on gene sets related to vaccine response, with the C2 subtype exhibiting significantly worse prognosis. While no statistically significant differences in tumor mutation burden (TMB) were observed across the three subtypes, the homologous recombination deficiency (HRD) score and mRNA stemness index (mRNAsi) were notably elevated in the C2 group compared to the others. Immune infiltration analysis indicated that the C2 subtype may have an increased presence of regulatory T (Treg) cells, potentially contributing to a more favorable response to combination therapies involving PARP inhibitors and immunotherapy. These findings offer a precision medicine approach for tailoring immunotherapy in ovarian cancer patients. Moreover, the C3 subtype demonstrated significantly lower expression levels of immune checkpoint genes, a pattern validated by independent datasets, and associated with a better prognosis. Further investigation revealed that the immune-related gene FCRL5 correlates with ovarian cancer prognosis, with in vitro experiments showing that it influences the proliferation and migration of the ovarian cancer cell line SKOV3.

PMID:39434163 | DOI:10.1186/s13048-024-01526-w

BMC Womens Health. 2024 Oct 21;24(1):567. doi: 10.1186/s12905-024-03406-3.

ABSTRACT

AIMS: This study aims to examine cases identified with endometrial polyp and carcinoma originating from polyps in patients presenting with gynaecological problems, and to highlight the significance of risk factors contributing to malignancy.

MATERIALS AND METHODS: The study comprised 203 patients who visited our clinic between January 2019 and 2024 with various gynaecological problems and were identified with endometrial polyps after a clinical, radiographic, and laboratory assessment. We retrospectively analysed data from 191 benign endometrial polyps and hyperplasia without atypia and 12 patients with endometrial polyps and underlying endometrial hyperplasia with atypia and/or endometrial carcinoma, diagnosed histopathologically after hysteroscopic resection, retrieved from our hospital’s electronic archive system. Two hundred three participants were tested in the study, with 191 classifieds with benign tumours and 12 diagnosed with malignant tumours and atypical endometrial hyperplasia (premalignant). Cases were chosen according on consistent criteria for age, BMI, gravida, parity, abortion, educational level, smoking habits, operation history, and co-morbidities. After determining the sample size for the malignant group, patients from the control group were selected to be included in the study. Initially, patients with similar age and BMI distributions were included into the study. Next, the cases were analysed for similarities in gravida, parity, and abortion parameters, and those that matched were chosen. Following this step, the educational status was compared for resemblance, and examples with matching educational status were chosen. Consequently, the study covered a total of 34 patients, with 12 identified with malignant tumours and atypical endometrial hyperplasia (premalignant) and 22 with benign tumours. Two groups of cases were diagnosed with endometrial polyp, and risk factors that may cause the development of endometrial polyp and underlying carcinoma: age, gravida, parity, abortion, education level, smoking, previous operation history, comorbidity, gynaecological complaints, fasting blood sugar, CRP values, haemoglobin, and haematocrit were evaluated in terms of endometrial polyp sizes, endometrial thickness level, and endometrial polyp localization. By examining the pathological risk factors of these cases, particularly during the premenopausal period, the goal is to predict endometrial cancer, the most prevalent gynaecological cancer in women, along with its antecedents, and implement preventive measures proactively.

RESULTS: Age, BMI, gravida, parity, number of abortions, educational status, smoking status, operation history, co-morbidity, and complaint variables did not exhibit a statistically significant difference between the groups (p > 0.05). It was revealed that the FBG level, CRP level, Polyp length and Endometrial thickness level of the malignant group were statistically significantly higher than the benign group (p < 0.01) (p < 0.05). Upon analysing the FBG distribution among groups, it is noted that the ODDS ratio is 10.20 for FBG values of 122.5 and above (95% CI: 1.97 – 52.78). Upon analysing the CRP distribution by groups, it is noted that the ODDS ratio is 231 for CRP values of 9.7 and above (95% CI: 13.15 – 4058.67). Upon analysing the distribution of Polyp length based on groups, it was determined that the ODDS ratio is 13.5 for Polyp lengths of 2.25 and above (95% CI: 2.47 – 73.71). Upon analysing the distribution of EM thickness based on groups, it is shown that the ODDS ratio is 5.25 for EM thicknesses of 11 and above (95% CI: 1.09 – 25.21).

CONCLUSION: Endometrial polyps are common benign growths that are typically not seen as cancer precursors but may be linked to cancer in people with advanced age. It is vital to remember that in cases of endometrial polyps, variables such as increasing polyp length, endometrial thickness, fasting glucose level, and elevated CRP levels are significant risk factors for the development of cancer associated with polyps.

PMID:39434154 | DOI:10.1186/s12905-024-03406-3

J Transl Med. 2024 Oct 21;22(1):955. doi: 10.1186/s12967-024-05751-1.

ABSTRACT

Numerous clinical trials for myasthenia gravis (MG) treatment have been conducted recently, with satisfactory cognitive and clinical results. However, due to the limited evidence for direct comparison of the safety and effectiveness of various drugs, there is a need for further exploration of the advantages and disadvantages of different monoclonal antibodies and immunosuppressants. Thus, in the present network meta-analysis (NMA), we aimed to compare the efficacy and safety of immunosuppressants and monoclonal antibodies in treating MG. We systematically searched for randomized controlled trials published in PubMed, Embase, Web of Science, and the Cochrane Library between January 1, 2000 and March 6, 2024. Statistical analyses were performed using R software (version 4.2.3), JAGS, and STATA (version 15.0). The surface under the cumulative ranking curve (SUCRA) value was calculated to assess the potential efficacy of each drug and the likelihood of adverse events (AEs), with higher SUCRA values indicating better efficacy or a lower likelihood of AEs. This NMA included 21 randomized controlled trials involving 13 drugs and 1,657 patients. Based on changes in Quantitative MG and MG Composite scores, batoclimab was most likely to exert the best therapeutic effects, with SUCRA values of 99% and 92%, respectively. Rozanolixzumab performed better than the other drugs in terms of the MG Activities of Daily Living score (85%). Eculizumab exhibited the highest potential in reducing the 15-item revised version of the MG Quality of Life score (96%). Regarding safety, belimumab had the highest SUCRA value (85%), demonstrating the lowest likelihood of AEs. In conclusion, all immunosuppressants and monoclonal antibodies analyzed in this study were more effective than the placebo in treating MG, with rozanolixzumab and batoclimab potentially being the most effective. Regarding safety, rozanolixzumab exhibited a higher likelihood of AEs than did placebo. The conclusions guide the clinical selection of effective drugs and offer insights for future drug experiments.

PMID:39434135 | DOI:10.1186/s12967-024-05751-1

Reprod Biol Endocrinol. 2024 Oct 21;22(1):129. doi: 10.1186/s12958-024-01300-z.

ABSTRACT

BACKGROUND: At present, embryologists are attempting to use conventional in vitro fertilization (cIVF) as an alternative to intracytoplasmic sperm injection (ICSI) for preimplantation genetic testing (PGT). However, the potential parental contamination origin of sperm cells and cumulus cells is considered the main limiting factor in the inability of cIVF embryos to undergo PGT.

METHODS: In this study, we established an IVF-PGTA assay for parental contamination tests with a contamination prediction model based on allele frequencies and linkage disequilibrium (LD) to compute the log-likelihood ratio (LLR) under competing ploidy hypotheses, and then verified its sensitivity and accuracy. Finally, comparisons of the effectiveness of SNP-based analysis and LLR-based IVF-PGTA among 40 cIVF embryos was performed, based on both statistical analysis of the parental contamination rate and chromosomal ploidy concordance rate between TE biopsy and ICM isolations.

RESULTS: With IVF-PGTA assay, biopsies with 10% maternal contamination could be detected accurately, and contamination caused by sperm cells could be eliminated completely. Utilizing LLR-based or single Nucleotide Polymorphism (SNP) -based analyses, our comprehensive examination of 40 clinically discarded fresh cIVF embryos revealed an absence of paternal contamination. Strikingly, the LLR-based analysis uniquely revealed a mere instance of 24% maternal contamination within the trophectoderm cell (TE) biopsy of 5* embryo. Furthermore, it was solely through this analysis that embryo (9-F) was identified as a triploid of paternal origin.

CONCLUSIONS: In this study, we developed a new bioinformatics analysis method for identifying parental contamination during IVF-PGT, especially for couples with nonmale factor infertility.

PMID:39434113 | DOI:10.1186/s12958-024-01300-z

World J Surg Oncol. 2024 Oct 21;22(1):276. doi: 10.1186/s12957-024-03562-8.

ABSTRACT

OBJECTIVE: Poly (ADP-ribose) polymerase (PARP) inhibitors such as olaparib and niraparib have shown promise in extending progression-free survival (PFS) in patients with platinum-sensitive recurrent (PSR) epithelial ovarian cancer. In this retrospective study, we aimed to present our own data on the effect of PARP inhibitors on PFS in recurrent epithelial ovarian cancer.

METHODS: 82 patients diagnosed with PSR epithelial ovarian, tubal, or primary peritoneal cancer between May 2017 and September 2023 were initially enrolled from our hospital. However, 16 patients had prior exposure to PARP inhibitors during primary treatment, and 11 were lost to follow-up. Consequently, the study focused on 55 eligible patients. PFS was compared between patients receiving PARP inhibitor maintenance therapy and those who did not.

RESULTS: Among the 55 patients with PSR epithelial ovarian cancer, 18 received olaparib as maintenance therapy, 19 received niraparib, and 18 opted for observation. PARP inhibitor therapy significantly extended PFS (mean 24.0 months) compared to observation (mean 9.0 months, p = 0.0005), regardless of BRCA mutation status (HR = 0.20, 95% CI: 0.08-0.50). Subgroup analysis showed no statistical difference between olaparib and niraparib. Additionally, there was no PFS difference based on BRCA mutation status within both PARP inhibitor groups.

CONCLUSION: Our retrospective study demonstrates that PARP inhibitor maintenance therapy, including olaparib and niraparib, significantly prolongs PFS in patients with PSR epithelial ovarian, tubal, or primary peritoneal cancer, These findings support the broad utilization of PARP inhibitors as a standard maintenance therapy for PSR epithelial ovarian cancer irrespective of BRCA mutation status.

PMID:39434111 | DOI:10.1186/s12957-024-03562-8

J Hematol Oncol. 2024 Oct 21;17(1):99. doi: 10.1186/s13045-024-01623-9.

ABSTRACT

BACKGROUND: Accurate and up-to-date estimates of the global cancer burden in adolescents and young adults (AYA) are scarce. This study aims to assess the global burden and trends of AYA cancer, with a focus on socioeconomic disparities, to inform global cancer control strategies.

METHODS: AYA cancer, defined as cancer occurring in individuals aged 15-39, was analyzed using data from the Global Burden of Disease (GBD) 2021 study and the Global Cancer Observatory (GLOBOCAN) 2022 project. We examined the global burden by age, sex, geographic location, and Human Development Index (HDI), as well as its temporal trends. Primary outcomes included age-standardized incidence and mortality rates (ASIR, ASMR) and the average annual percent change (AAPC).

RESULTS: In 2022, an estimated 1,300,196 incidental cases and 377,621 cancer-related deaths occurred among AYAs worldwide, with an ASIR of 40.3 per 100,000 and an ASMR of 11.8 per 100,000. The most common cancers were breast, thyroid, and cervical, while the leading causes of death were breast, cervical, and leukemia. The incidence and mortality were disproportionately higher among females (ASIR: 52.9 for females vs. 28.3 for males; ASMR: 13.1 for females vs. 10.6 for males). Countries with higher HDI experienced a higher incidence of AYA cancers (ASIR: 32.0 [low HDI] vs. 54.8 [very high HDI]), while countries with lower HDI faced a disproportionately higher mortality burden (ASMR: 17.2 [low HDI] vs. 8.4 [very high HDI]) despite their relatively low incidence. Disproportionality and regression measures highlighted significant HDI-related inequalities. AYA cancer incidence was stable from 2000 to 2011 (AAPC: – 0.04) but increased from 2012 to 2021 (AAPC: 0.53), driven by growing gonadal and colorectal cancers. Mortality decreased substantially from 2000 to 2011 (AAPC: – 1.64), but the decline slowed from 2012 (AAPC: – 0.32) probably due to increased deaths from gonadal cancers. These trends varied by sex, cancer type, geography, and HDI.

CONCLUSION: AYA cancers present a significant and growing global burden, with marked disparities across sex, geographic locations, and HDI levels. Policymakers should prioritize equitable resource allocation and implement targeted interventions to reduce these inequalities, particularly in low-HDI regions and with regard to gonadal cancers.

PMID:39434099 | DOI:10.1186/s13045-024-01623-9

Environ Health. 2024 Oct 22;23(1):89. doi: 10.1186/s12940-024-01127-6.

ABSTRACT

BACKGROUND: Current evidence linking long-term exposure to fine particulate matter (PM_2.5) exposure and mortality is primarily based on persons that live in the same residence, city and/or country throughout the study, with few residential moves or relocations. We propose a novel method to quantify the health impacts of PM_2.5 for United States (US) diplomats who regularly relocate to international cities with different PM_2.5 levels.

METHODS: Life table methods were applied at an individual-level to US mortality statistics using the World Health Organization’s database of city-specific PM_2.5 annual mean concentrations. Global Burden of Disease concentration-response (C-R) functions were used to estimate cause-specific mortality and days of life lost (DLL) for a range of illustrative 20-year diplomatic assignments for three age groups. Time lags between exposure and exposure-related mortality risks were applied. Sensitivity analysis of baseline mortality, exposure level, C-R functions and lags was conducted. The effect of mitigation measures, including the addition of air purifiers, was examined.

RESULTS: DLL due to PM_2.5 exposure for a standard 20-year assignment ranged from 0.3 days for diplomats’ children to 84.1 days for older diplomats. DLL decreased when assignments in high PM_2.5 cities were followed by assignments in low PM_2.5 cities: 162.5 DLL when spending 20 years in high PM_2.5 cities compared to 62.6 DLL when spending one of every four years (5 years total) in a high PM_2.5 city for older male diplomats. Use of air purifiers and improved home tightness in polluted cities may halve DLL due to PM_2.5 exposure. The results were highly sensitive to lag assumptions: DLL increased by 68% without inception lags and decreased by 59% without cessation lags for older male diplomats.

CONCLUSION: We developed a model to quantify health impacts of changing PM_2.5 exposure for a population with frequent relocations. Our model suggests that alternating assignments in high and low PM_2.5 cities may help reduce PM_2.5-related mortality burdens. Adding exposure mitigation at home may help reduce PM_2.5 related mortality. Further research on outcome-specific lag structures is needed to improve the model.

PMID:39434094 | DOI:10.1186/s12940-024-01127-6

J Inflamm (Lond). 2024 Oct 21;21(1):40. doi: 10.1186/s12950-024-00414-w.

ABSTRACT

BACKGROUND: Trauma and infection induce emergency granulopoiesis. Counts of immature granulocytes and transcriptional pathways of terminal granulocytic differentiation in blood are elevated in sepsis but correlate with disease severity. This limits their performance as sepsis biomarkers in critically ill patients. We hypothesized that activation of these pathways in sepsis is attributable to immature low-density (LD) rather than mature high-density (HD) granulocytes.

METHODS: We included patients with sepsis and systemic inflammatory response syndrome (SIRS) of comparable disease severity, and additionally septic shock, on intensive or intermediate care unit admission. Blood granulocyte isolation by CD15 MicroBeads was followed by density-gradient centrifugation. Flow cytometry was used to determine counts of developmental stages (precursors) and their relative abundancies in total, HD, and LD granulocytes. Five degranulation markers were quantified in plasma by multiplex immunoassays. A set of 135 genes mapping granulocyte differentiation was assayed by QuantiGene™ Plex. CEACAM4, PLAC8, and CD63 were analyzed by qRT-PCR. Nonparametric statistical tests were applied.

RESULTS: Precursor counts appeared higher in sepsis than SIRS but did not correlate with disease severity for early immature and mature granulocytes. Precursor subpopulations were enriched at least ten-fold in LD over HD granulocytes without sepsis-SIRS differences. Degranulation markers in blood were comparable in sepsis and SIRS. Higher expression of early developmental genes in sepsis than SIRS was more pronounced in LD and less in HD than total granulocytes. Only the cell membrane protein encoding genes CXCR2 and CEACAM4 were more highly expressed in SIRS than sepsis. By qRT-PCR, the azurophilic granule genes CD63 and PLAC8 showed higher sepsis than SIRS levels in LD granulocytes and PLAC8 also in total granulocytes where its discriminatory performance resembled C-reactive protein (CRP).

CONCLUSIONS: Transcriptional programs of early terminal granulocytic differentiation distinguish sepsis from SIRS due to both higher counts of immature granulocytes and elevated expression of early developmental genes in sepsis. The sustained expression of PLAC8 in mature granulocytes likely accounts for its selection in the whole blood SeptiCyte™ LAB test. Total granulocyte PLAC8 rivals CRP as sepsis biomarker. However, infection-specific transcriptional pathways, that differentiate sepsis from sterile stress-induced granulocytosis more reliably than CRP, remain to be identified.

PMID:39434093 | DOI:10.1186/s12950-024-00414-w

BMC Oral Health. 2024 Oct 21;24(1):1260. doi: 10.1186/s12903-024-05029-4.

ABSTRACT

BACKGROUND: The materials used in root canal filling and radiotherapy (RT) application can affect the load-to-failure of the teeth. This study aimed to compare the load-to-failure of the teeth filled with AH Plus (AHP) or AH Plus bioceramic (AHPB) before or after 60 Gy- and 70 Gy-dose radiotherapy.

MATERIALS AND METHODS: One hundred and ten maxillary incisors were endodontically prepared up to ProTaper Next X4 instruments. The teeth were randomly divided into 5 main groups as: non-irradiated, root canal treatment (RCT) before 60 Gy radiotherapy, RCT before 70 Gy radiotherapy, RCT after 60 Gy radiotherapy, RCT after 70 Gy radiotherapy. These groups were divided into 2 subgroups for filling material: AHP ve AHPB. After filling and radiotherapy procedures, the teeth were fixed on the thermoplastic mask plane. The plane were placed in the middle of a rectangular prism shaped glass phantom, and irradiated via a linear accelerator device. The teeth were then embedded in cylindrical acrylic blocks and the force (N) that caused the fracture was recorded under the Universal testing device. Student t-test was used for statistical comparisons. Statistical significance level was determined as p < 0.05.

RESULTS: After 70 Gy dose radiotherapy, the group filled with AHPB showed statistically significantly lower fracture strength than the group filled with AHP (p < 0.05). In the control group, before 60 Gy RT group, after 60 Gy RT group, and before 70 Gy RT group, the sealers had statistically significantly similar load-to-failure. (p > 0.05).

CONCLUSION: The group filled with AHPB caused a lower fracture strength than the group filled with AHP following a 70 Gy dose of RT. The sealers in the control group, before 60 Gy RT group, after 60 Gy RT group, and before 70 Gy RT group exhibited comparable load-to-failure values.

PMID:39434091 | DOI:10.1186/s12903-024-05029-4

BMC Public Health. 2024 Oct 21;24(1):2895. doi: 10.1186/s12889-024-20399-8.

ABSTRACT

BACKGROUND: Air quality health index (AQHI), as a developed air quality risk communication tool, has been proved to be more accurate in predicting air quality related health risks than air quality index (AQI) by previous studies. However, the standard method to construct AQHI is summing the excess risks of single-pollutant models directly, which may ignore the joint effect of air pollutant mixtures.

METHODS: In this study, a new method which could solve the aforementioned problem, Analytic hierarchy process (AHP), was introduced. Based on this method, we constructed the respiratory health related AQHI using years of life lost (YLL) as indicator of health outcome and compared its validity with AQI.

RESULTS: There was a correlation between daily AQI and AQHI in 2019 (R² = 0.830, P < 0.01), and the chi-square test between the two excellent rates showed a statistically significant difference (χ² = 4.156, P < 0.05). Both AQI and AQHI were correlated with the daily respiratory YLL (P < 0.01), however, the coefficient of AQHI was larger than those of AQI.

CONCLUSIONS: This study indicated that compared with AQI, the constructed AQHI based on AHP may predict the health risk of air pollution more effectively. AHP may become a new method to construct AQHI which needs to be proved by taking into consideration by more studies.

PMID:39434079 | DOI:10.1186/s12889-024-20399-8