Оценка финансовых показателей, характеризующих международные пассажирские перевозки транспортной организации

Материалы XII Междунар. науч. конф. студентов, магистрантов, аспирантов и молодых ученых, Гомель, 16–17 мая 2019 г

The Association between Serum Serine and Glycine and Related-Metabolites with Pancreatic Cancer in a Prospective Cohort Study

Background: Serine and glycine play an important role in the folate-dependent one-carbon metabolism. The metabolism of serine and glycine has been shown to be associated with cancer cell proliferation. No prior epidemiologic study has investigated the associations for serum levels of serine and glycine with pancreatic cancer risk. Methods: We conducted a nested case-control study involved 129 incident pancreatic cancer cases and 258 individually matched controls within a prospective cohort study of 18,244 male residents in Shanghai, China. Glycine and serine and related metabolites in pre-diagnostic serum were quantified using gas chromatography-tandem mass spectrometry. A conditional logistic regression method was used to evaluate the associations for serine, glycine, and related metabolites with pancreatic cancer risk with adjustment for potential confounders. Results: Odds ratios (95% confidence intervals) of pancreatic cancer for the highest quartile of serine and glycine were 0.33 (0.14–0.75) and 0.25 (0.11–0.58), respectively, compared with their respective lowest quartiles (both p’s < 0.01). No significant association with risk of pancreatic cancer was observed for other serine- or glycine related metabolites including cystathionine, cysteine, and sarcosine. Conclusion: The risk of pancreatic cancer was reduced by more than 70% in individuals with elevated levels of glycine and serine in serum collected, on average, more than 10 years prior to cancer diagnosis in a prospectively designed case-control study. These novel findings support a protective role of serine and glycine against the development of pancreatic cancer in humans that might have an implication for cancer prevention.publishedVersio

The End of Roe v. Wade: Implications for Women\u27s Mental Health and Care

The Supreme Court decision in Dobbs v. Jackson in June 2022 reversed precedent which had previously protected abortion prior to fetal viability as a universal right within the United States. This decision almost immediately led to abortion restrictions across 25 states. The resulting lack of access to abortion care for millions of pregnant people will have profound physical and mental health consequences, the full effects of which will not be realized for years to come. Approximately 1 in 5 women access abortions in the U.S. each year. These women are diverse and represent all American groups. The Supreme court decision, however, will affect populations that have and continue to be marginalized the most. Forcing pregnant individuals to carry unwanted pregnancies worsens health outcomes and mortality risk for both the perinatal individual and the offspring. The US has one of the highest maternal mortality rates and this rate is projected to increase with abortion bans. Abortion policies also interfere with appropriate medical care of pregnant people leading to less safe pregnancies for all. Beyond the physical morbidity, the psychological sequelae of carrying a forced pregnancy to term will lead to an even greater burden of maternal mental illness, exacerbating the already existing maternal mental health crisis. This perspective piece reviews the current evidence of abortion denial on women\u27s mental health and care. Based on the current evidence, we discuss the clinical, educational, societal, research, and policy implications of the Dobbs v. Jackson Supreme Court decision

Digital health policy and programs for hospital care in Vietnam: scoping review

Background: There are a host of emergent technologies with the potential to improve hospital care in low- and middle-income countries such as Vietnam. Wearable monitors and artificial intelligence–based decision support systems could be integrated with hospital-based digital health systems such as electronic health records (EHRs) to provide higher level care at a relatively low cost. However, the appropriate and sustainable application of these innovations in low- and middle-income countries requires an understanding of the local government’s requirements and regulations such as technology specifications, cybersecurity, data-sharing protocols, and interoperability. Objective: This scoping review aims to explore the current state of digital health research and the policies that govern the adoption of digital health systems in Vietnamese hospitals. Methods: We conducted a scoping review using a modification of the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. PubMed and Web of Science were searched for academic publications, and Thư Viện Pháp Luật, a proprietary database of Vietnamese government documents, and the Vietnam Electronic Health Administration website were searched for government documents. Google Scholar and Google Search were used for snowballing searches. The sources were assessed against predefined eligibility criteria through title, abstract, and full-text screening. Relevant information from the included sources was charted and summarized. The review process was primarily undertaken by one researcher and reviewed by another researcher during each step. Results: In total, 11 academic publications and 20 government documents were included in this review. Among the academic studies, 5 reported engineering solutions for information systems in hospitals, 2 assessed readiness for EHR implementation, 1 tested physicians’ performance before and after using clinical decision support software, 1 reported a national laboratory information management system, and 2 reviewed the health system’s capability to implement eHealth and artificial intelligence. Of the 20 government documents, 19 were promulgated from 2013 to 2020. These regulations and guidance cover a wide range of digital health domains, including hospital information management systems, general and interoperability standards, cybersecurity in health organizations, conditions for the provision of health information technology (HIT), electronic health insurance claims, laboratory information systems, HIT maturity, digital health strategies, electronic medical records, EHRs, and eHealth architectural frameworks. Conclusions: Research about hospital-based digital health systems in Vietnam is very limited, particularly implementation studies. Government regulations and guidance for HIT in health care organizations have been released with increasing frequency since 2013, targeting a variety of information systems such as electronic medical records, EHRs, and laboratory information systems. In general, these policies were focused on the basic specifications and standards that digital health systems need to meet. More research is needed in the future to guide the implementation of digital health care systems in the Vietnam hospital setting

Intratumoral Genetic and Functional Heterogeneity in Pediatric Glioblastoma.

Pediatric glioblastoma (pGBM) is a lethal cancer with no effective therapies. To understand the mechanisms of tumor evolution in this cancer, we performed whole-genome sequencing with linked reads on longitudinally resected pGBM samples. Our analyses showed that all diagnostic and recurrent samples were collections of genetically diverse subclones. Clonal composition rapidly evolved at recurrence, with less than 8% of nonsynonymous single-nucleotide variants being shared in diagnostic-recurrent pairs. To track the origins of the mutational events observed in pGBM, we generated whole-genome datasets for two patients and their parents. These trios showed that genetic variants could be (i) somatic, (ii) inherited from a healthy parent, or (iii) de novo in the germlines of pGBM patients. Analysis of variant allele frequencies supported a model of tumor growth involving slow-cycling cancer stem cells that give rise to fast-proliferating progenitor-like cells and to nondividing cells. Interestingly, radiation and antimitotic chemotherapeutics did not increase overall tumor burden upon recurrence. These findings support an important role for slow-cycling stem cell populations in contributing to recurrences, because slow-cycling cell populations are expected to be less prone to genotoxic stress induced by these treatments and therefore would accumulate few mutations. Our results highlight the need for new targeted treatments that account for the complex functional hierarchies and genomic heterogeneity of pGBM. SIGNIFICANCE: This work challenges several assumptions regarding the genetic organization of pediatric GBM and highlights mutagenic programs that start during early prenatal development.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/9/2111/F1.large.jpg.Wellcome Trust Royal Societ

Neighborhood Socioeconomic Status, Depression, and Health Status in the Look AHEAD (Action for Health in Diabetes) Study

Depression and diminished health status are common in adults with diabetes, but few studies have investigated associations with socio-economic environment. The objective of this manuscript was to evaluate the relationship between neighborhood-level SES and health status and depression. Individual-level data on 1010 participants at baseline in Look AHEAD (Action for Health in Diabetes), a trial of long-term weight loss among adults with type 2 diabetes, were linked to neighborhood-level SES (% living below poverty) from the 2000 US Census (tracts). Dependent variables included depression (Beck Inventory), and health status (Medical Outcomes Study (SF-36) scale). Multi-level regression models were used to account simultaneously for individual-level age, sex, race, education, personal yearly income and neighborhood-level SES. Overall, the % living in poverty in the participants' neighborhoods varied, mean = 11% (range 0-67%). Compared to their counterparts in the lowest tertile of neighborhood poverty (least poverty), those in the highest tertile (most poverty) had significantly lower scores on the role-limitations(physical), role limitations(emotional), physical functioning, social functioning, mental health, and vitality sub-scales of the SF-36 scale. When evaluating SF-36 composite scores, those living in neighborhoods with more poverty had significantly lower scores on the physical health (β-coefficient [β] = -1.90 units, 95% CI: -3.40,-0.039), mental health (β = -2.92 units, -4.31,-1.53) and global health (β = -2.77 units, -4.21,-1.33) composite scores. In this selected group of weight loss trial participants, lower neighborhood SES was significantly associated with poorer health status. Whether these associations might influence response to the Look AHEAD weight loss intervention requires further investigation

Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells

Pediatric ependymomas are highly recurrent tumors resistant to conventional chemotherapy. Telomerase, a ribonucleoprotein critical in permitting limitless replication, has been found to be critically important for the maintenance of tumor-initiating cells (TICs). These TICs are chemoresistant, repopulate the tumor from which they are identified, and are drivers of recurrence in numerous cancers. In this study, telomerase enzymatic activity was directly measured and inhibited to assess the therapeutic potential of targeting telomerase. Telomerase repeat amplification protocol (TRAP) (n = 36) and C-circle assay/telomere FISH/ATRX staining (n = 76) were performed on primary ependymomas to determine the prevalence and prognostic potential of telomerase activity or alternative lengthening of telomeres (ALT) as telomere maintenance mechanisms, respectively. Imetelstat, a phase 2 telomerase inhibitor, was used to elucidate the effect of telomerase inhibition on proliferation and tumorigenicity in established cell lines (BXD-1425EPN, R254), a primary TIC line (E520) and xenograft models of pediatric ependymoma. Over 60 % of pediatric ependymomas were found to rely on telomerase activity to maintain telomeres, while no ependymomas showed evidence of ALT. Children with telomerase-active tumors had reduced 5-year progression-free survival (29 +/- A 11 vs 64 +/- A 18 %; p = 0.03) and overall survival (58 +/- A 12 vs 83 +/- A 15 %; p = 0.05) rates compared to those with tumors lacking telomerase activity. Imetelstat inhibited proliferation and self-renewal by shortening telomeres and inducing senescence in vitro. In vivo, Imetelstat significantly reduced subcutaneous xenograft growth by 40 % (p = 0.03) and completely abolished the tumorigenicity of pediatric ependymoma TICs in an orthotopic xenograft model. Telomerase inhibition represents a promising therapeutic approach for telomerase-active pediatric ependymomas found to characterize high-risk ependymomas.Canadian Institutes of Health Research [MOP 82727]info:eu-repo/semantics/publishedVersio

Neighborhood and weight-related health behaviors in the Look AHEAD (Action for Health in Diabetes) Study

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown that neighborhood factors are associated with obesity, but few studies have evaluated the association with weight control behaviors. This study aims to conduct a multi-level analysis to examine the relationship between neighborhood SES and weight-related health behaviors.</p> <p>Methods</p> <p>In this ancillary study to Look AHEAD (Action for Health in Diabetes) a trial of long-term weight loss among individuals with type 2 diabetes, individual-level data on 1219 participants from 4 clinic sites at baseline were linked to neighborhood-level data at the tract level from the 2000 US Census and other databases. Neighborhood variables included SES (% living below the federal poverty level) and the availability of food stores, convenience stores, and restaurants. Dependent variables included BMI, eating patterns, weight control behaviors and resource use related to food and physical activity. Multi-level models were used to account for individual-level SES and potential confounders.</p> <p>Results</p> <p>The availability of restaurants was related to several eating and weight control behaviors. Compared to their counterparts in neighborhoods with fewer restaurants, participants in neighborhoods with more restaurants were more likely to eat breakfast (prevalence Ratio [PR] 1.29 95% CI: 1.01-1.62) and lunch (PR = 1.19, 1.04-1.36) at non-fast food restaurants. They were less likely to be attempting weight loss (OR = 0.93, 0.89-0.97) but more likely to engage in weight control behaviors for food and physical activity, respectively, than those who lived in neighborhoods with fewer restaurants. In contrast, neighborhood SES had little association with weight control behaviors.</p> <p>Conclusion</p> <p>In this selected group of weight loss trial participants, restaurant availability was associated with some weight control practices, but neighborhood SES was not. Future studies should give attention to other populations and to evaluating various aspects of the physical and social environment with weight control practices.</p

Serum S100A6 Concentration Predicts Peritoneal Tumor Burden in Mice with Epithelial Ovarian Cancer and Is Associated with Advanced Stage in Patients

BACKGROUND:Ovarian cancer is the 5th leading cause of cancer related deaths in women. Five-year survival rates for early stage disease are greater than 94%, however most women are diagnosed in advanced stage with 5 year survival less than 28%. Improved means for early detection and reliable patient monitoring are needed to increase survival. METHODOLOGY AND PRINCIPAL FINDINGS:Applying mass spectrometry-based proteomics, we sought to elucidate an unanswered biomarker research question regarding ability to determine tumor burden detectable by an ovarian cancer biomarker protein emanating directly from the tumor cells. Since aggressive serous epithelial ovarian cancers account for most mortality, a xenograft model using human SKOV-3 serous ovarian cancer cells was established to model progression to disseminated carcinomatosis. Using a method for low molecular weight protein enrichment, followed by liquid chromatography and mass spectrometry analysis, a human-specific peptide sequence of S100A6 was identified in sera from mice with advanced-stage experimental ovarian carcinoma. S100A6 expression was documented in cancer xenografts as well as from ovarian cancer patient tissues. Longitudinal study revealed that serum S100A6 concentration is directly related to tumor burden predictions from an inverse regression calibration analysis of data obtained from a detergent-supplemented antigen capture immunoassay and whole-animal bioluminescent optical imaging. The result from the animal model was confirmed in human clinical material as S100A6 was found to be significantly elevated in the sera from women with advanced stage ovarian cancer compared to those with early stage disease. CONCLUSIONS:S100A6 is expressed in ovarian and other cancer tissues, but has not been documented previously in ovarian cancer disease sera. S100A6 is found in serum in concentrations that correlate with experimental tumor burden and with clinical disease stage. The data signify that S100A6 may prove useful in detecting and/or monitoring ovarian cancer, when used in concert with other biomarkers

Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling

Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy1,2,3. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations2. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes1,3. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1)1,3,4. Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat.This work was supported by an Alex's Lemonade Stand Young Investigator Award (S.C.M.), The CIHR Banting Fellowship (S.C.M.), The Cancer Prevention Research Institute of Texas (S.C.M., RR170023), Sibylle Assmus Award for Neurooncology (K.W.P.), the DKFZ-MOST (Ministry of Science, Technology & Space, Israel) program in cancer research (H.W.), James S. McDonnell Foundation (J.N.R.) and NIH grants: CA154130 (J.N.R.), R01 CA169117 (J.N.R.), R01 CA171652 (J.N.R.), R01 NS087913 (J.N.R.) and R01 NS089272 (J.N.R.). R.C.G. is supported by NIH grants T32GM00725 and F30CA217065. M.D.T. is supported by The Garron Family Chair in Childhood Cancer Research, and grants from the Pediatric Brain Tumour Foundation, Grand Challenge Award from CureSearch for Children’s Cancer, the National Institutes of Health (R01CA148699, R01CA159859), The Terry Fox Research Institute and Brainchild. M.D.T. is also supported by a Stand Up To Cancer St. Baldrick’s Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113)