Lipoproteins and metabolites in diagnosing and predicting Alzheimer's disease using machine learning.

BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disorder that poses a substantial economic burden. The Random forest algorithm is effective in predicting AD; however, the key factors influencing AD onset remain unclear. This study aimed to analyze the key lipoprotein and metabolite factors influencing AD onset using machine-learning methods. It provides new insights for researchers and medical personnel to understand AD and provides a reference for the early diagnosis, treatment, and early prevention of AD. METHODS: A total of 603 participants, including controls and patients with AD with complete lipoprotein and metabolite data from the Alzheimer's disease Neuroimaging Initiative (ADNI) database between 2005 and 2016, were enrolled. Random forest, Lasso regression, and CatBoost algorithms were employed to rank and filter 213 lipoprotein and metabolite variables. Variables with consistently high importance rankings from any two methods were incorporated into the models. Finally, the variables selected from the three methods, with the participants' age, sex, and marital status, were used to construct a random forest predictive model. RESULTS: Fourteen lipoprotein and metabolite variables were screened using the three methods, and 17 variables were included in the AD prediction model based on age, sex, and marital status of the participants. The optimal random forest modeling was constructed with "mtry" set to 3 and "ntree" set to 300. The model exhibited an accuracy of 71.01%, a sensitivity of 79.59%, a specificity of 65.28%, and an AUC (95%CI) of 0.724 (0.645-0.804). When Mean Decrease Accuracy and Gini were used to rank the proteins, age, phospholipids to total lipids ratio in intermediate-density lipoproteins (IDL_PL_PCT), and creatinine were among the top five variables. CONCLUSIONS: Age, IDL_PL_PCT, and creatinine levels play crucial roles in AD onset. Regular monitoring of lipoproteins and their metabolites in older individuals is significant for early AD diagnosis and prevention.

Incidence and trends of hepatic cancer among children and adolescents in the United States from 2000 to 2017: Evidence from the Surveillance, Epidemiology, and End Results registry data.

OBJECTIVE: Primary liver tumors are rare pediatric malignancies. Knowledge of the epidemiology of pediatric liver tumors is limited. This study aims to present the national incidence trends of pediatric liver tumors over 18 years, according to sociodemographic and histological subtype variation. METHODS: The Surveillance, Epidemiology, and End Results registry was queried from 2000 to 2017 for 1,099 patients between ages 0 and 19 with liver tumors. Age-standardized incidence rates by age, sex, and race/ethnicity were examined among histological subtypes. Annual percentage change (APC) was calculated via joinpoint regression for various sociodemographic and histotype subgroups. RESULTS: An increase of age-adjusted incidence rate of pediatric hepatic cancers was observed between 2000 and 2017 (APC, 1.7% [95% confidence interval or CI: 0.6%-2.8%], p-value = 0.006), which may likely attribute to the increasing incidence of hepatoblastoma and mesenchymal tumors (APC, 2.5% [95% CI: 1.1%-3.8%], p-value = 0.001). The incidence trend of hepatocellular carcinoma remained stable in the study period. The non-Hispanic Asian/Pacific Islander children and adolescents had a higher risk of hepatic tumors (incidence rate ratio or IRR, 1.42 [95% CI: 1.16-1.72], p-value = 0.0007) when compared with the non-Hispanic white subgroup, while a non-Hispanic black child was associated with a lower incidence rate (IRR, 0.64 [95% CI: 0.50-0.80], p-value < 0.0001). Significantly lower hepatic tumor incidence occurred in females than males, with an incidence rate ratio of 0.69 (95% CI: 0.61-0.78; p-value < 0.0001). Hepatic tumor incidence was also significantly lower in those aged 1-4 years (IRR, 0.47 [95% CI: 0.40-0.54]; p-value < 0.001) and 5-19 years (IRR, 0.09 [95% CI: 0.08-0.10]; p-value < 0.001) when compared with the youngest age group aged less than 1 year. These significant differences were also detected for the subgroup of hepatoblastoma and mesenchymal liver tumors but less among hepatocellular carcinomas (all p-values less than 0.0001). CONCLUSION: Continued increasing incidence of pediatric hepatoblastoma and mesenchymal liver tumors was discovered and warranted further investigation. Additional findings include a lower incidence of hepatic cancer among non-Hispanic black individuals and higher incidence of hepatic cancer in non-Hispanic Asian/Pacific Islander, male, and aged 1-4-year children and adolescents.

Pulmonary resection of residual lesions of pulmonary metastasis from gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate the prognosis and recurrence in patients with residual lesions of pulmonary metastasis from gestational trophoblastic neoplasia after initial treatment, and to explore the clinical significance of pulmonary resection. METHODS: A retrospective analysis was performed on 606 patients with residual lesions from pulmonary metastasis after receiving standardized chemotherapy as initial treatment in Peking Union Medical College Hospital from January 2002 to December 2018. Patients were divided into surgery (51 patients) and non-surgery (555 patients) groups. The prognosis of these patients was compared. Risk factors affecting recurrence were analyzed to explore the effect of pulmonary resection. RESULTS: Among low risk patients, complete remission rate was 100% and recurrence rate was <1% in both groups. Among high risk patients, complete remission and recurrence rates were 93.5% and 10.3% in the surgery group and 94.7% and 14.3% in the non-surgery group, respectively. There was no significant difference in prognostic features between the two groups (all p>0.05). No significant difference was found in recurrence rates based on recurrence risk factors (≥3.2 cm residual lung lesions, prognosis score ≥9.0, and drug resistance) between the two groups (all p>0.05). CONCLUSION: After standardized chemotherapy, pulmonary resection was not necessary for initially treated stage III gestational trophoblastic neoplasia patients whose blood ß human chorionic gonadotropin levels normalized and residual lung lesions remained stable. These patients should be closely monitored during follow-up, regardless of the size of the residual lung lesions or high/low risk score, especially within a year after complete remission.

Knowledge, psychological impacts, and protective behaviours during the first wave of the COVID-19 pandemic among Chinese residents in Canada with dependent school-age children: a cross-sectional online study.

BACKGROUND: The purpose of this study was to describe the knowledge, protective behaviours, and psychological impact of COVID-19 on Chinese residents in Canada, as the emotional and behavioural impacts of the pandemic have not been intensively studied amongst these populations. It was important to determine whether having dependent school-age children (DSAC) aged 16 or under was associated with adverse psychological impacts amongst the Chinese residents living in the country. METHODS: In April 2020, 757 eligible participants were recruited through a snowball sampling to complete an online survey related to the COVID-19 pandemic. Psychological, behavioural, and sociodemographic variables were collected and first analyzed using descriptive and univariate statistics. Multiple logistic regression analyses were performed to further confirm the observed significant associations in bivariate analyses for selected psychological outcome variables. RESULTS: Seven hundred forty-two participants who responded to the "dependent school-age children" question were included in the analysis. Most of them identified as females (65.8%) and 77.2% included receiving a university degree or higher. There were no significant differences in COVID-19 knowledge between those living with or without DSAC. However, participants with DSAC were more likely to perceive themselves as being at greater risk of contracting COVID-19 (p = .023); therefore, having a higher chance of adopting protective behaviours (e.g., hand washing, sanitizing frequently or disinfecting work and living spaces (p < .05), elevated risks of depression (p = .007), and stress (p = .010), compared to those without DSAC. CONCLUSIONS: Predominantly, the Chinese residents in Canada with dependent school-age children were more likely to report the negative psychological impacts of the pandemic. These findings warrant further investigations that may contribute to informing key stakeholders about the identification and implementation of policies and interventions to support the needs of parents with young children, during and after the pandemic.

Prevalence of Oral Exostoses in Northern China During the Past Six Millennia-From a Sex and Age Perspective.

This study is intended to investigate oral exostoses of 5 sample populations, spanning over 6000 years, from the same region of Northern China, to determine the significance of sex and age on the development of oral exostoses during each time period. The samples analyzed were 306 dry jaws from human skeletons, which were excavated from 4 archeological sites: Banpo (6700-5600 y BP), Shaolingyuan (3000 y BP), Shanren (2200 y BP), and Chang'an (1000-1300 y BP), as well as the modern Xi'an district. The sex and the age of the samples at death were estimated. The degree of buccal exostosis (BE), torus mandibularis (TM), and torus palatinus (TP) and the TP shape were recorded. The results showed BEs in the Banpo and Chang'an regions, TMs in the Banpo region were more often diagnosed in males than in females. Conversely, females in Shaolingyuan showed a higher prevalence and severity of TM than that in males. The occurrence of BEs in the Shanren and Xi'an regions, TMs in the Banpo, Chang'an, and Xi'an regions, as well as TPs in the Banpo region significantly increased with age at death. In conclusion, sex differences and increasing trends with age in relation to oral exostoses were found in samples from Northern China during the past six millennia.

An aging-related signature predicts favorable outcome and immunogenicity in lung adenocarcinoma.

Aging has been demonstrated to play vital roles in the prognosis and treatment efficacy of cancers, including lung adenocarcinoma (LUAD). This novel study aimed to construct an aging-related risk signature to evaluate the prognosis and immunogenicity of LUAD. Transcriptomic profiles and clinical information were collected from a total of 2518 LUAD patients from 12 independent cohorts. The risk signature was developed by combining specific gene expression with the corresponding regression coefficients. One cohort treated with the immune checkpoint inhibitor (ICI) was also used. Subsequently, a risk signature was developed based on 21 aging-related genes. LUAD patients with low-risk scores exhibited improved survival outcomes in both the discovery and validation cohorts. Further immunology analysis revealed elevated lymphocyte infiltration, decreased infiltration of immune-suppressive cells, immune response-related pathways, and favorable ICI predictor enrichment in the low-risk subgroup. Genomic mutation exploration indicated the enhanced mutation burden and higher mutation rates in significantly driver genes of TP53, KEAP1, SMARCA4, and RBM10 were enriched in patients with a low-risk signature. In the immunotherapeutic cohort, it was observed that low-risk aging scores were markedly associated with prolonged ICI prognosis. Overall, the estimated aging signature proved capable of evaluating the prognosis, tumor microenvironment, and immunogenicity, which further provided clues for tailoring prognosis prediction and immunotherapy strategies, apart from promoting individualized treatment plans for LUAD patients.

Pediatric neurological cancer incidence and trends in the United States, 2000-2018.

OBJECTIVE: To characterize the epidemiological trends and sociodemographic variation of pediatric and adolescent neurological cancers by histological subtypes over time in the USA. METHODS: A total of 16,511 patients aged 0-19 years diagnosed with neurological cancers between 2000 and 2018, including 13,024 with central nervous system (CNS) neoplasms and 3,487 with neuroblastomas, were identified from 18 registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Incidence trends over time and incidence rate ratios by race/ethnicity, sex, and age were calculated for histological subtype. Age-standardized incidence rates (ASIR) by year of diagnosis and average annual percent changes (AAPC) were calculated to measure incidence rates. ASIR by race/ethnicity, sex, and age were calculated to examine the incidence variation by these factors. RESULTS: Overall, age-standardized annual incidence per 100,000 person-years increased from 2.20 in 2000 to 3.21 in 2018 with an AAPC of 1.4% (95% confidence interval or CI: 0.5% to 2.4%); however, that of Hispanic decreased from 2.93 in 2000 to 2.59 in 2018 with an AAPC of - 0.8% (95% CI: - 1.2% to - 0.3%). Non-Hispanic Black children and adolescents had a statistically significantly lower incidence than non-Hispanic White peers both for CNS neoplasms (incidence rate ratio or IRR: 0.67; 95% CI: 0.63 to 0.71) and neuroblastomas (IRR: 0.75; 95% CI: 0.68 to 0.83). Females generally had a lower incidence than males, especially among those with intracranial and intraspinal embryonal tumors (IRR: 0.69; 95% CI: 0.64 to 0.75). The highest incidence rate of neuroblastoma was among newborns aged less than 1 year, and the highest incidence rate of CNS neoplasms was among children aged 1-4 years. CONCLUSION: The incidence of neurological cancers has increased among children and adolescents from 2000 to 2018, with wide variation across demographic groups.

Expression of B7 family checkpoint proteins in cervical cancer.

The role of programmed cell death-ligand 1 (PD-L1) in cervical cancer has been widely investigated; however, the influences of other inhibitory B7 family members are poorly understood. We investigated the expression of PD-L1, B7 homolog 3 (B7-H3), B7-H4, and V-domain Ig suppressor of T-cell activation (VISTA) and their association with the clinicopathological features and outcomes of a large cohort of 673 patients with squamous cell carcinoma or adenocarcinoma of the uterine cervix. The positivity rates for PD-L1 (combined positive score ≥1), B7-H3 in tumor cells (TCs), B7-H4 (exclusively in TCs), VISTA in immune cells (ICs), and VISTA in TCs were 57.9%, 62.8%, 44.8%, 92.6%, and 4.8%, respectively, in 606 primary cervical cancer samples. Co-expression of PD-L1 with B7-H3 in TCs and with B7-H4 and VISTA in ICs was observed in 38.8%, 25.4%, and 57.9% of samples, respectively. B7-H3 in TCs and B7-H4 and VISTA in ICs were observed in 58.1%, 46.6%, and 83.1% of PD-L1-negative samples, respectively. These proteins were observed more frequently in squamous cell carcinomas and in moderately to poorly differentiated carcinomas. VISTA (in ICs) and B7-H4 were more frequent in primary tumors than in recurrent counterparts and correlated with improved survival; in contrast, B7-H3 positivity in TCs was less frequent in primary tumors and correlated with short disease-specific survival. Co-expression of B7-H4 and VISTA in ICs was an independent predictor of favorable outcomes overall and among patients with PD-L1-negative tumors. These data indicate that B7 family proteins exhibit differing expression patterns, distributions, and prognostic implications in cervical cancer. Furthermore, the co-expression of PD-L1 with other checkpoint proteins suggests that PD-1/PD-L1 blockade combined with modulating other immune checkpoints may present a novel therapeutic approach for cervical cancer. Future studies are needed to validate prognostic values of B7 family proteins and explore their biological roles in this malignancy.

Prediagnostic consumption of vitamin D, calcium and dairy products and colorectal cancer survival: results from the Newfoundland Colorectal Cancer Registry Cohort Study.

Vitamin D, Ca and dairy products are negatively associated with colorectal cancer (CRC) incidence, but little is known of their influence on CRC survival. To investigate prediagnostic intakes of vitamin D, Ca and dairy products for their relevance to CRC prognosis, we analysed 504 CRC patients enrolled in the Newfoundland Colorectal Cancer Registry Cohort Study who were diagnosed for the first time with CRC between 1999 and 2003. Follow-up for mortality and cancer recurrence was through April 2010. Data on diet and lifestyle factors were gathered via a validated, semi-quantitative FFQ and a Personal History Questionnaire. Multivariate Cox models estimated hazard ratios (HR) and 95 % CI for the relationship of prediagnostic intakes of vitamin D, Ca and dairy products with all-cause mortality (overall survival, OS) and disease-free survival (DFS) among CRC patients. We found that prediagnostic Ca intake from foods, but not total Ca intake, was negatively associated with all-cause mortality (HR for Q2 v. Q1, 0·44; 95 % CI, 0·26, 0·75). An inverse relationship was also seen in a dose-response fashion for prediagnostic cheese intake (HR for Q4 v. Q1, 0·57, 95 % CI, 0·34, 0·95, Ptrend = 0·029). No evidence for modification by sex, physical activity, alcohol drinking and cigarette smoking was observed. In summary, high prediagnostic intakes of cheese and Ca from foods may be associated with increased survival among CRC patients. By manipulating diet, this study may contribute to the development of novel therapies that add to the armamentarium against CRC. Replication studies are required before any nutritional interventions are made available.

Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial.

BACKGROUND: Treatment options for patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia are scarce. The synergistic antitumour effect of immunotherapy and antiangiogenic drugs has been shown in many solid tumours. This phase 2 trial evaluated the activity and safety of camrelizumab (PD-1 inhibitor) plus apatinib (VEGF receptor inhibitor) in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. METHODS: This was a single-arm, open-label, phase 2 trial, done at a single tertiary health-care centre in Beijing, China. Women (18-70 years) with high-risk (International Federation of Gynecology and Obstetrics score ≥7) chemorefractory or relapsed gestational trophoblastic neoplasia who had received at least two lines of previously unsuccessful multidrug chemotherapy regimens and had an Eastern Cooperative Oncology Group performance status of 0-2 were eligible for inclusion. Patients received 4-week cycles of intravenous camrelizumab 200 mg every 2 weeks plus oral apatinib 250 mg once per day until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed according to serum human chorionic gonadotrophin concentration. Activity and safety were analysed in all patients who received at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT04047017. FINDINGS: Between Aug 7, 2019, and March 18, 2020, 20 patients enrolled; 19 (95%) were diagnosed with choriocarcinoma and one (5%) had placental site trophoblastic tumour. The median follow-up duration was 18·5 months (IQR 14·6-20·9). The objective response rate was 55% (95% CI 32-77); ten (50%; 95% CI 27-73) patients had complete response. The most common grade 3 treatment-related adverse events were hypertension (five [25%] patients), rash (four [20%] patients), neutropenia (two [10%]), leukocytopenia (two [10%]), and aspartate aminotransferase increase (two [10%]). One patient had a treatment-related serious adverse event (aspartate aminotransferase 19-times higher than the upper limit of normal). No grade 4 or 5 treatment-related adverse events were reported. INTERPRETATION: Camrelizumab plus apatinib showed promising antitumour activity and acceptable toxicity and could be a salvage therapy option for the treatment of high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. Immune checkpoint inhibitors combined with chemotherapy for heavily-treated patients and upfront use of camrelizumab plus apatinib for patients with high-risk gestational trophoblastic neoplasia are under investigation in phase 2 trials. FUNDING: National Natural Science Foundation of China, Jiangsu Hengrui Pharmaceuticals.

Results with Floxuridine, Actinomycin D, Etoposide, and Vincristine in Gestational Trophoblastic Neoplasias with International Federation of Gynecology and Obstetrics Scores ≥5.

BACKGROUND: 5-fluorouracil-based multiagent chemotherapy has been used as the primary treatment for high-risk gestational trophoblastic neoplasia (GTN) in China for a few decades. This study aims to assess the efficacy and toxicity of floxuridine, actinomycin D, etoposide, and vincristine (FAEV) as a primary treatment for patients with GTN who had International Federation of Gynecology and Obstetrics (FIGO) scores ≥5. MATERIALS AND METHODS: A total of 207 patients with GTN who had FIGO scores ≥5 were treated with FAEV as first-line chemotherapy at Peking Union Medical College Hospital between January 2002 and December 2017. Complete remission (CR), resistance, survival, toxicity, and reproductive outcomes were analyzed. RESULTS: Of the 207 patients treated with FAEV, 9 (4.3%) required a change of chemotherapy owing to toxicity and 1 (0.5%) died of cerebral hernia 5 weeks after commencing treatment. The remaining 197 patients were assessable to determine the response to FAEV; among them, 168 (85.3%) achieved CR with FAEV and 29 (14.7%) developed resistance to FAEV. The 5-year overall survival rate of the entire cohort was 97.4%. Grade 3-4 neutropenia, thrombocytopenia, and anemia occurred in 28.4%, 6.8%, and 6.2% of cycles, respectively. No acute toxicity-related deaths occurred. Five patients developed acute myeloid leukemia 10-50 months after exposure to chemotherapy; another patient developed duodenal cancer 2 years after completing therapy. Sixty-one patients who preserved fertility wanted to become pregnant; 56 of them conceived. CONCLUSION: The FAEV regimen is an effective primary treatment for patients with GTN who have FIGO scores ≥5 and has predictable and manageable toxicity. IMPLICATIONS FOR PRACTICE: The most commonly used multiagent chemotherapy for high-risk gestational trophoblastic neoplasia (GTN) is etoposide, methotrexate and actinomycin D/cyclophosphamide and vincristine (EMA/CO) worldwide. However, 5-fluorouracil-based multiagent chemotherapy has been used as a primary treatment for high-risk GTN in China for a few decades. This study evaluated the efficacy and toxicity of floxuridine, actinomycin D, etoposide, and vincristine (FAEV) as a primary treatment for patients with GTN who have International Federation of Gynecology and Obstetrics (FIGO) scores ≥5. The study's data demonstrated that FAEV as a primary treatment achieved favorable outcomes for patients with FIGO scores ≥5. Toxicities that result from the FAEV regimen are predictable and manageable. The FAEV regimen may provide another option for the treatment of GTN.

The tumor-stroma ratio is an independent predictor of survival in patients with 2018 FIGO stage IIIC squamous cell carcinoma of the cervix following primary radical surgery.

OBJECTIVE: To determine the value of the tumor-stroma ratio (TSR) while identifying prognostic factors in patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIIC squamous cell carcinoma of the cervix following primary radical surgery. METHODS: Three hundred eighty-four patients with node-positive squamous cell carcinoma of the cervix (2018 FIGO stage IIIC) who underwent radical surgery between January 2005 and December 2016 were included in this retrospective study. The TSRs were assessed on hematoxylin and eosin-stained tumor slides and classified as stroma-low (<50% stroma) or stroma-high (≥50% stroma). RESULTS: Sixty-seven patients were categorized as stroma-high; they had shorter disease-free survival (DFS) and overall survival (OS) periods than did their stroma-low counterparts. On multivariate analysis, a tumor size ≥4 cm, ≥3 metastatic lymph nodes, and stroma-high status were independent predictors of shorter DFS and OS. These factors were incorporated into a prognostic scoring system in which patients were categorized into low- (score 0), intermediate- (score 1), and high-risk (scores 2-3) groups. The scoring system differentiated DFS and OS well (C-index = 0.65, 95% confidence interval, 0.59-0.72; and C-index = 0.65, 95% confidence interval, 0.59-0.72, respectively). CONCLUSIONS: The TSR is an independent prognostic factor, and our prognostic scoring system that incorporates this parameter exhibits good discriminative ability for both recurrence and survival in patients with 2018 FIGO stage IIIC cervical cancer after radical surgery. The TSR is a potentially novel clinicopathological variable for predicting the prognoses of these patients contingent on the validation of our findings.

Sociodemographics and their impacts on risk factor awareness and beliefs about cancer and screening: results from a cross-sectional study in Newfoundland and Labrador.

BACKGROUND: Our objective was to examine cancer risk factor awareness and beliefs about cancer treatment, outcomes, and screening, and how these are mediated by sociodemographic variables, among Newfoundland and Labrador residents. METHODS: Participants aged 35 to 74 were recruited through Facebook advertising, and a self-administered online questionnaire was used to collect data. Descriptive statistics, Spearman rank correlations, and multivariate logistic regression analyses were performed. RESULTS: Of the 1048 participants who responded and met the inclusion criteria for this study, 1019 were selected for this analysis. Risk factor recognition was generally good, though several risk factors had poor awareness: being over 70 years old (53.4% respondents aware), having a low-fiber diet (65.0%), and drinking more than 1 unit of alcohol per day (62.8%). Our results showed that the participants' awareness of risk factors was significantly associated with higher income level (rs = 0.237, P <  0.001), higher education (rs = 0.231, P <  0.001), living in rural regions (rs = 0.163, P <  0.001), and having a regular healthcare provider (rs = 0.081, P = 0.010). Logistic regression showed that among NL residents in our sample, those with higher income, post-secondary education, those in very good or excellent health, and those with a history of cancer all had higher odds of having more positive beliefs about cancer treatment and outcomes. Those with a history of cancer, and those with very good or excellent health, also had higher odds of having more positive beliefs about cancer screening. Finally, compared to Caucasian/white participants, those who were non-Caucasian/white had lower odds of having more positive beliefs about cancer screening. CONCLUSION: Among adults in NL, there was poor awareness that low-fiber diets, alcohol, and age are risk factors for cancer. Lower income and education, rural residence, and not having a health care provider were associated with lower risk factor awareness. We also found a few associations between sociodemographic factors and beliefs about cancer treatment and outcomes or screening. We stress that while addressing awareness is necessary, so too is improving social circumstances of disadvantaged groups who lack the resources necessary to adopt healthy behaviours.

Clinical characteristics and prognosis of ultra high-risk gestational trophoblastic neoplasia patients: A retrospective cohort study.

OBJECTIVE: The gestational trophoblastic neoplasia (GTN) patients with the International Federation of Gynecology and Obstetrics (FIGO) score≥12 are defined as ultra high-risk GTN. This study aims to investigate the clinical characteristics, the treatment efficiency, and the prognosis of ultra high-risk GTN patients. METHODS: Between January 2002 and December 2015, medical record data of 143 GTN patients with FIGO score≥12 at Peking Union Medical College Hospital (PUMCH) were reviewed. Ratios were compared using chi-square test, and prognostic risk factors were analyzed by univariate analysis and multivariate analysis. RESULTS: Among the 143 ultra high-risk GTN patients, 94 (65.7%) patients had achieved complete remission and 15.9% (15/94) patients relapsed after complete remission. The 5-year overall survival (OS) rate of the entire cohort approached 67.9%. The results of the multivariate analysis revealed that non-molar antecedent pregnancy [Relative risk (RR) 4.689, 95% CI 1.448-15.189, P=0.010], brain metastases (RR 2.280, 95% CI 1.248-4.163, P=0.007), previous failed multiagent chemotherapy (RR 5.345, 95% CI 2.222-12.857, P=0.000) and surgery (RR 0.336, 95% CI 0.177-0.641, P=0.001) all had influence on the prognosis of ultra high-risk GTN patients. CONCLUSIONS: GTN patients with FIGO score≥12 have a poor prognosis. More emphasis should be placed on non-molar antecedent pregnancy, brain metastases, and previous multiagent chemotherapy failure. Moreover, salvage surgery may improve the prognosis. Floxuridine-based multiagent chemotherapy is effective with manageable toxicity for ultra high-risk GTN patients.

[Factors related to clinical pregnancy outcomes of in vitro fertilization-embryo transfer in women with secondary infertility].

OBJECTIVE: To investigate the factors related to clinical pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET) in women with secondary infertility. METHODS: The clinical, laboratory and follow-up data of 1129 cycles in 1099 patients with secondary infertility undergoing IVF-ET in Women's Hospital, Zhejiang University School of Medicine between July 2012 to July 2014 were retrospectively reviewed. The factors related to pregnancy outcomes were analyzed by univariate and logistic regression methods. The clinical pregnancy rates in women with different age and different number of embryos transferred were compared. The clinical outcomes of stimulation with gonadotropin releasing hormone (GnRH) agonist long protocol, GnRH agonist short protocol and GnH antagonist protocol were evaluated in secondary infertile patients aged ≥ 40 years. RESULTS: Among 1129 cycles, 376 cases (33.30%) had clinical pregnancy and 753 cases (66.70%) had no clinical pregnancy. There were significant differences in age, body mass index, basal follicle-stimulating hormone level, antral follicle number,paternal age and number of embryos transferred between pregnancy and no pregnancy groups (P<0.05); while only maternal age (OR=0.900, 95% CI: 0.873~0.928, P<0.001) and the number of embryos transferred (OR=2.248, 95% CI: 1.906~2.652, P<0.001) were the independent factors affecting the clinical pregnancy outcome of IVF-ET. There was no significant difference in clinical pregnancy rate between women aged 30~40 years with two embryos transferred and those aged<30 years with two or three embryos transferred(P>0.05). There were no significances in clinical pregnancy rate among women aged ≥ 40 years using GnRH agonist long protocol,GnRH agonist short protocol and GnRH antagonist protocol for stimulation (P>0.05). CONCLUSION: Maternal age and number of embryos transferred have independent effect on IVF-ET clinical pregnancy outcome of secondary infertile women. We suggest that no more than two embryos should be transferred for women in their thirties to minimize the risk of multiple pregnancy while still having an acceptable pregnancy rate. The pregnancy rate of patients over 40 years decreases significantly, and there is no difference in pregnancy rate by using GnRH agonist long protocol, GnRH agonist short protocol or GnRH antagonist protocol.

Metal ion stimulation-related gene signatures correlate with clinical and immunologic characteristics of glioma.

Background: Environmental factors serve as one of the important pathogenic factors for gliomas. Yet people focus only on the effect of electromagnetic radiation on its pathogenicity, while metals in the environment are neglected. This study aimed to investigate the relationship between metal ion stimulation and the clinical characteristics and immune status of GM patients. Methods: Firstly, mRNA expression profiles of GM patients and normal subjects were obtained from Chinese GM Genome Atlas (CGGA) and Gene Expression Omnibus (GEO) to identify differentially expressed metal ion stimulation-related genes(DEMISGs). Secondly, two molecular subtypes were identified and validated based on these DEMISGs using consensus clustering. Diagnostic and prognostic models for GM were constructed after screening these features based on machine learning. Finally, supervised classification and unsupervised clustering were combined to classify and predict the grade of GM based on SHAP values. Results: GM patients are divided into two different response states to metal ion stimulation, M1 and M2, which are related to the grade and IDH status of the GM. Six genes with diagnostic value were obtained: SLC30A3, CRHBP, SYT13, DLG2, CDK1, and WNT5A. The AUC in the external validation set was higher than 0.90. The SHAP value improves the performance of classification prediction. Conclusion: The gene features associated with metal ion stimulation are related to the clinical and immune characteristics of transgenic patients. XGboost/LightGBM Kmeans has a higher classification prediction accuracy in predicting glioma grades compared to using purely supervised classification techniques.

Ketamine alleviates fear memory and spatial cognition deficits in a PTSD rat model via the BDNF signaling pathway of the hippocampus and amygdala.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with traumatic stress experiences. This condition can be accompanied by learning and cognitive deficits. Studies have demonstrated that ketamine can rapidly and significantly alleviate symptoms in patients with chronic PTSD. Nonetheless, the effects of ketamine on neurocognitive impairment and its mechanism of action in PTSD remain unclear. METHODS: In this study, different concentrations of ketamine (5, 10, 15, and 20 mg/kg, i.p.) were evaluated in rat models of single prolonged stress and electrophonic shock (SPS&S). Expression levels of brain-derived neurotrophic factor (BDNF) and post-synaptic density-95 (PSD-95) in the hippocampus (HIP) and amygdala (AMG) were determined by Western blot analysis and immunohistochemistry. RESULTS: The data showed that rats subjected to SPS&S exhibited significant PTSD-like cognitive impairment. The effect of ketamine on SPS&S-induced neurocognitive function showed a U-shaped dose effect in rats. A single administration of ketamine at a dosage of 10-15 mg/kg resulted in significant changes in behavioral outcomes. These manifestations of improvement in cognitive function and molecular changes were reversed at high doses (15-20 mg/kg). CONCLUSION: Overall, ketamine reversed SPS&S-induced fear and spatial memory impairment and the down-regulation of BDNF and BDNF-related PSD-95 signaling in the HIP and AMG. A dose equal to 15 mg/kg rapidly reversed the behavioral and molecular changes and promoted the amelioration of cognitive dysfunction. The enhanced association of BDNF signaling with PSD-95 effects could be involved in the therapeutic efficiency of ketamine for PTSD.

The research landscape of the quality of life or psychological impact on gynecological cancer patients: A bibliometric analysis.

Background: Gynecological cancer is one of the most common cancers in women. The quality of life (QoL) or psychological impact has emerged as an outcome indicator in many clinical trials of gynecological cancer and gained much concern in the clinical setting at the start of the 21st century. Our paper conducted a bibliometric analysis of QoL or psychological impact on gynecological cancer patients to show the status and hotspots. Methods: Related publications from 2000 to 2022 were included by screening from the Web of Science Core Collection (WOSCC) on 26 June 2022. The bibliometrics was analyzed and visualized by bibliometrix R-package, VOSviewer, and CiteSpace V. Results: A total of 6,479 publications were included in our study. The publications in this field were increased annually. The United States (n = 2,075) was the country with the most published papers. Sydney University (n = 167) was the most productive affiliation. Gynecologic Oncology and Journal of Clinical Oncology were the most relevant and most cited sources, respectively. The article written by Bray F et al. has the highest citation. Kim J and Aaronson NK ranked first in most productive author and most co-cited author, respectively. The keywords "mortality", "fertility preservation", and "palliative care" have bursts till 2022, which represented the frontiers of this field. Conclusion: Our study provides an overall analysis of QoL or psychological impact on gynecological cancer patients, which can serve as a reference in future research.

Bioinformatic analysis identifies the immunological profile of turner syndrome with different X chromosome origins.

Introduction: Turner syndrome (TS) is a chromosomal disorder that affects phenotypic females who have one intact X chromosome and complete or partial absence of the second sex chromosome in association with one or more clinical manifestations. However, the immunological profile of TS with different X chromosome origins is incompletely understood. Methods: In this study, transcriptomic expression profiles of 26 TS (45,X) samples and 10 normal karyotype (46,XX) samples derived from GSE46687 cohort were employed. Differentially expressed immune-related genes (DEIRGs) between monosomy X TS patients with different X chromosome origins and normal females were investigated respectively. Subsequently, functional annotation, protein-protein interaction (PPI) network analysis, immunocyte infiltration evaluation, tissue-specific gene expression and Weighted gene co expression network analysis (WGCNA) were performed to explore the immunological characteristic in TS with different X chromosome origins. Results: 34 and 52 DEIRGs were respectively identified in 45,Xm and 45,Xp patients compared with normal individuals. The identified DEIRGs in Xm group were significantly enriched in pathways associated with cancer. In Xp TS patients, the most enriched signals were immune response-related. A majority of genes involved in the above pathways were downregulated. PPI analysis identified 4 (FLT3, IL3RA, CSF2RA, PIK3R3) and 6 (PDGFRB, CSF2, IL5, PRL, CCL17 and IL2)hub genes for Xm and Xp groups, respectively. CIBERSORT results showed that the proportion of Tregs in the Xm group and the naive B cells and resting NK cells in the Xp group significantly increased, respectively. Tissue-specific expression results indicated that BDCA4+_dentritic cells and CD19+ B cells were the prominent specific expressed tissues in Xp patients. Results of WGCNA support the above analysis. Conclusions: This study aims at studying the immunological characteristics of TS with different X chromosome origins. Pathways in cancer in Xm group and immune response in Xp group were suppressed. 4 and 6 hub IRGs were identified as biomarkers for Xm and Xp patients, respectively. B cells played important roles in Xp patients. Further studies are needed to draw more attention to the functional validation of these hub genes and the roles of B cells.

A mutational signature and significantly mutated driver genes associated with immune checkpoint inhibitor response across multiple cancers.

Immune checkpoint inhibitor (ICI) treatments dramatically prolong the survival outcomes of several advanced cancers. However, as multiple studies reported, only a subset of patients could benefit from the ICI treatment. In this study, we aim to uncover novel molecular biomarkers predictive of immunotherapy efficacy across multiple cancers. Pre-treatment somatic mutational profiles and immunotherapy clinical information were obtained from 1097 samples of multiple cancers, including melanoma, non-small cell lung cancer (NSCLC), clear cell renal cell carcinoma (ccRCC), bladder carcinoma (BLCA), and head and neck squamous cell carcinoma (HNSCC). Mutational signatures, molecular subtypes, and significantly mutated genes (SMGs) were determined, and their connections with ICI response and outcome were also evaluated. We extracted a total of six mutational signatures across all samples. Among, a mutational signature featured by T > C substitutions was identified to associate with an ICI resistance. A molecular subtype determined based on mutational activities was connected with a significantly improved ICI response rate and outcome. Totaling 50 SMGs were identified, and we observed that patients with COL11A1 or COL4A6 mutations exhibited a superior ICI treatment efficacy than those without such mutations. In this study, we uncovered several novel molecular determinants of cancer immunotherapy response under a multiple-cancer setting, which provides clues for enrolling patients to receive immunotherapy and customizing personalized treatment strategies.