Correction For Testing Research Articles

Salience and feasibility of enacting rough draft math: Teachers’ voices about productive and powerful variations

AbstractRough draft math [RDM] (Jansen, 2020a) occurs when a teacher invites students to share their in-progress thinking and provides opportunities for students to revise their thinking. RDM could be viewed as an approach to ambitious teaching because it is a practice when teachers elicit and respond to students’ thinking to support their learning, which is productive, and their positive identity development, which is powerful. The purpose of this study was to identify salient and feasible enactments of rough draft math, as described by teachers after they have learned about RDM through a book study and/or professional development. We interviewed 32 teachers in eight states in the USA, and we identified variations among the two most feasible and salient enactments of RDM: (1) inviting students to revise and (2) purposeful task selection and implementation. Variations in revising enactments included providing students with structured or unstructured revision opportunities and different ways teachers incorporated revising into their assessment practices (either test corrections or student self-assessment). Variations in task selection included modifying curricular tasks or using instructional routines intentionally. Variations in task implementation included implementing tasks to reinforce content or develop new understandings. We developed conjectures about the ways in which these variations could provide powerful or productive opportunities for students.

Rapid imaging approach for marine controlled-source electromagnetic with deployed transmission system

The marine controlled-source electromagnetic (MCSEM) method is widely used in gas hydrate exploration. For the deployed transmission system of MCSEM, it is equipped with two groups of orthogonal transmission antennas to obtain more comprehensive information. The mainstream processing method involves using a single rotated field component for conventional 2D inversion to obtain the resistivity model. However, data preprocessing and inversion speed are relatively slow, making it difficult to quickly or nearly real-time identify gas hydrate anomalous areas. In order to leverage the benefits of multi-component data and obtain a potential real-time imaging method for the future, we have developed a rapid imaging technique for the deployed transmission system to obtain apparent resistivity pseudosections. The current and electromagnetic field data in different directions are replaced by rotational invariants, and an approximate formula is derived based on the half-space formula and test corrections. This formula maps the apparent resistivity and field data. Results from model tests demonstrate that the apparent resistivity pseudosections can qualitatively identify reservoirs, particularly in the lateral range. In 2015, the South China Sea gas hydrate exploration project acquired data using the deployed transmission system. The pseudosections reveal that the rapid imaging method can directly detect resistivity anomalies and serve as an approximate and effective display method for deployed transmission system of MCSEM, thanks to its simplicity, efficiency, and low computational cost.

Look-Alike Detection using Deep Convolutional Neural Networks for Ocean Oil Spills

The marine and coastal ecosystems are placed in grave danger whenever there is a spill of oil. For the sake of protecting future generations, the authorities need a dependable mechanism that allows them to respond quickly and effectively to oil spills. As a result of their consistency also effectiveness in a wide series of weather and light situations, synthetic aperture radar (SAR) sensors are frequently utilized for this determination. The dark spots that are typically associated with oil spills remain easy for SAR sensors to spot, but it may be difficult to differentiate them from other objects or phenomena. A great number of methods have been outlined in order to automatically differentiate and categories these dark spots. The results are frequently unable to be compared with one another because of the heterogeneous nature of the data collected. It is often difficult to fine-tune settings or extract meaningful information because SAR images remain often classified through a solo label that is applicable to the entire picture. Because of this, the process of dealing with the images is made more difficult. The Random Forest Classifier and deep convolutional neural networks (also known as DCNNs) are examples of approaches that have been suggested as potential workarounds for these constraints. In addition, we make available to the public a search-and-rescue photo library that might serve as a standard for the growth of upcoming oil spill recognition tools. On the dataset that was provided, a number of well-known DCNN segmentation models as well as the Random Forest technique are evaluated and compared with one another. When compared to other approaches, it was discovered that Random Forest had the best test correctness and the quickest implication time. Additionally, the dataset is used to explore and explain the challenges of the provided issue, which in this case is identifying between genuine and fabricated oil spills. These investigations and demonstrations are carried out with the help of the dataset. According to their training and evaluation on the dataset that was provided to them, DCNN segmentation models, when paired with a Random Forest classifier, did quite well when attempting to detect oil spills. The novel method is anticipated to be of significant use in subsequent research pertaining to the identification of oil spills and the dispensation of SAR images.

Changes in the TMS-evoked potential N100 in the dorsolateral prefrontal cortex as a function of depression severity in adolescents

Studies using transcranial magnetic stimulation with simultaneous electroencephalography (TMS-EEG) revealed an imbalance between cortical excitation and inhibition (E/I) in the dorsolateral prefrontal cortex (DLPFC) in depression. As adolescence is a developmental period with an increase in depression prevalence and profound neural changes, it is crucial to study the relationship between depression and cortical excitability in adolescence. We aimed to investigate the cortical excitability of the DLPFC in adolescents with depression and a dependency of the TMS-evoked potential N100 on the depression severity. 36 clinical patients (12–18 years of age; 21 females) with a major depressive episode were assessed twice in a longitudinal design: shortly after admission (T0) and after six weeks of intervention (T1). GABA-B-mediated cortical inhibition in the left and right DLPFC, as assessed by the N100, was recorded with EEG. Significantly higher depression scores were reported at T0 compared to T1 (p < 0.001). N100 amplitudes were significantly increased (i.e., more negative) at T0 compared to T1 (p = 0.03). No significant hemispheric difference was found in the N100 component. The correlation between the difference in depression severity and the difference in N100 amplitudes (T0–T1) obtained during stimulation of the left DLPFC did not remain significant after correction for testing in both hemispheres. Higher N100 amplitudes during a state of greater depression severity are suggestive of an E/I imbalance in the DLPFC in adolescents with an acute depressive episode. The N100 reduction potentially reflects a normalization of DLPFC over inhibition in association with decreased depressive symptomatology, indicating severity dependency.

Performance Evaluation Method of Library Knowledge Management Based on Data Mining

With the development of information technology and computer technology, the work of the library is becoming more and more digitized and networked. This article mainly studies the performance evaluation method of library knowledge management based on data mining. This paper uses attribute-oriented induction algorithm to mine generalized features. First, scan the entire data set to obtain different values of all attributes. Statistics, classification, and analysis of historical records help to understand the usage of books and periodicals and perform predictive analysis. This article uses statistical weighted weight calculation formula to calculate the library knowledge management ability evaluation index weight. The evaluation of the knowledge management ability of the library mainly adopts the questionnaire survey method, and the knowledge management status of the library is deeply understood in the form of interviews on the spot, and the obtained evaluation data and materials of the knowledge management ability of the library are organized and statistics. In order to prevent the model from remembering the patterns of the training set too deeply, to make the model more general, and to adapt to unknown data well, we use the test set to rest the model. The part of the data set that has not been used in the process of modeling and testing correction can be used to estimate the effect of the model, or to compare the effect of the model. For expert value, the value of the office is 1.02, which is approximately equal to 1, which means that the value and cost of the office are basically equal in the knowledge service of the library. The results show that the combination of knowledge management and university library management will help to form a systematic theoretical framework and behavioral model framework in the research of knowledge management models and strategies in university libraries.

Abstract 3353: Discovery and validation of orphan noncoding RNA profiles across multiple cancers in TCGA and two independent cohorts

Abstract Small non-coding RNAs (sncRNAs) have established roles as post-transcriptional regulators of cancer pathogenesis. We recently reported a novel and previously unannotated class of cancer-specific sncRNAs in breast cancer and demonstrated that breast cancer cells exploit a specific sncRNA to promote cancer metastasis. However, the extent to which these sncRNAs, which we have collectively termed orphan non-coding RNAs (oncRNAs), are present in other cancer types is unknown. To address this question and define a high-confidence set of oncRNAs, we used smRNA-seq data from 6 cancer sites (breast, colorectal, kidney, liver, lung, and stomach) and their corresponding normal tissues from The Cancer Genome Atlas (TCGA; 4,445 cancer, 431 normal) and identified a total of 144,695 oncRNAs that are significantly present in cancer and largely absent in normal tissue (Fisher’s Exact Test and Benjamini-Hochberg correction, FDR &amp;lt; 0.1). To evaluate if this set of TCGA-derived oncRNAs could be validated in independent datasets, we examined smRNA-seq data from two large independent cohorts comprising these same cancer and normal tissue types (Indivumed, Hamburg, Germany). Cohort A consists of 4,024 samples (2,245 cancer, 1,779 normal) and cohort B consists of 2,874 samples (2,063 cancer; 811 normal). oncRNAs in these cohorts were annotated following the same procedure used for TCGA data. TCGA-derived oncRNAs were considered validated in the independent cohorts if they were present in a significantly higher number of cancer samples compared to adjacent normal tissue samples. In cohort A, 140,191 (96.9%) of TCGA-derived oncRNAs were detected in at least one sample, of which 74,634 (51.6%) were validated as oncRNAs. In cohort B, 140,147 (96.9%) oncRNAs were observed and 68,366 (47.2%) were validated. The degree of overlap between the validated oncRNAs in each cohort was significant, with 54,294 (37.5%) overlapping oncRNAs (hypergeometric test, P=0). We also found that oncRNAs are informative of cancer tissue of origin, demonstrating the existence of consistent cancer-specific oncRNA expression profiles in independent studies. Using the TCGA-derived oncRNAs as features, we trained an eXtreme Gradient Boosting (XGB) model on TCGA data to classify cancer samples by the 6 tissues of origin. The TCGA-trained model showed high performance when evaluated on both cohorts A and B, achieving accuracies of 91.5% (95% CI: 90.3%-92.7%) and 96% (94.7%-97%), respectively. For comparison, this model achieved an accuracy of 96% (94.5%-97.2%) on held-out TCGA data (80/20 train/test split). Our results show a robust validation of TCGA-derived oncRNAs in external, independently sourced and processed cancer tissue cohorts across a heterogeneous set of cancer sites. Our machine learning model also demonstrates that oncRNA profiles can be used to predict cancer tissue of origin with high generalizability and accuracy. Citation Format: Jeffrey Wang, Helen Li, Lisa Fish, Kimberly H. Chau, Patrick Arensdorf, Hani Goodarzi, Babak Alipanahi. Discovery and validation of orphan noncoding RNA profiles across multiple cancers in TCGA and two independent cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3353.

Abstract 5793: Comprehensive characterization of FGF/FGFR alterations in invasive breast cancers

Abstract BACKGROUND FGFR signaling is central for cancer cell proliferation, migration, angiogenesis, and survival. The frequency and type of FGF/FGFR aberrations are not well-characterized across invasive breast cancer subtypes and metastatic sites of disease. In hormone receptor positive breast cancers, FGFR1 amplification correlates with early progression on endocrine therapy and promotes resistance to CDK4/6 inhibition. Our study evaluated the incidence and characterization of FGF alterations in invasive breast cancers and examined differences based on histologic subtype, molecular subtype and site. METHODS Breast cancer samples underwent molecular profiling by Caris Life Sciences. Analyses included NGS of DNA (592 Gene Panel, NextSeq, and WES, NovaSEQ), and IHC (Caris Life Sciences, Phoenix, AZ). Biomarker results were compiled from cases within the breast cohort including data from any sequencing panel, gene expression/RNA seq panel, and IHC. All results listed below were statistically significant (p &amp;lt; 0.05) as determined by chi-square test and Benjamini Hochberg correction. RESULTS 12058 breast cancer tumors were analyzed: 4189 from primary breast specimens (35%) and 7869 from metastatic sites (65%). 4305 (36%) were ductal and 671 (6%) were lobular histology with remaining other/unknown. 6413 (53%) were HR+HER2-, 3504 (29%) were triple negative, 403 (3%) were HR+HER2+ and 363 (3%) were HR-HER2+ with 1375 (13%) of unknown subtype. In the entire cohort, the most commonly amplified genes were FGF19 (11.49%), FGF3 (10.75%), FGF4 (9.98%), CCND1 (12.36%), and FGFR1 (9.08%). FGFR1-4 amplification was present in 11.01% of all cases. FGF19 amplification was more prevalent in lobular breast cancer compared to ductal (12.1% vs 9.1%). FGF19, FGF23, FGF3, FGF4, FGF6 amplification varied across molecular subtypes being most prevalent in HR+/HER2- (15.7%), HR+/HER2+ (12.1%), and least prevalent in HR-/HER+ tumors (3.4%). FGFR1 amplification was most common among FGFR1-4 amplifications and most prevalent in HR+HER2- (12%). Across metastatic sites, FGF ligands displayed different patterns of amplification with FGF19, FGF3 and FGF4 amplification most prevalent in liver and bone metastases. FGFR1 amplification was statistically different across metastatic sites and most prevalent in liver metastases (16%) followed by bone (10%). Patients receiving CDK4/6 inhibitors with FGFR1 amplification had shorter time on treatment than FGFR1 wild type (HR = 0.892, p = 0.03). CONCLUSION FGF alterations in invasive breast cancers vary by molecular subtype and site of disease. FGFR1, FGF19, FGF23, FGF3, FGF4, and FGF6 amplifications were statistically different across subtypes (most prevalent in HR+/HER2- and HR+/HER2+) and metastatic sites (most prevalent in liver and bone metastases). The prevalence in HR+ subtypes lend support to the role of FGF in endocrine resistance. Citation Format: Kush C. Gaur, Justin Tiu-Lim, Julie McGrath, Phil Walker, Michael Korn, Joanne Xiu, Arielle Heeke, Virginia Kaklamani, Antoinette Tan, Janice Lu, Darcy Spicer, Evanthia Roussos-Torres, Priya Jayachandran, Audrey Saghian, Amir Goldkorn, Irene Kang. Comprehensive characterization of FGF/FGFR alterations in invasive breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5793.

Influence of the Human Lipidome on Epicardial Fat Volume in Mexican American Individuals.

IntroductionCardiovascular disease (CVD) is the leading cause of mortality worldwide and is the leading cause of death in the US. Lipid dysregulation is a well-known precursor to metabolic diseases, including CVD. There is a growing body of literature that suggests MRI-derived epicardial fat volume, or epicardial adipose tissue (EAT) volume, is linked to the development of coronary artery disease. Interestingly, epicardial fat is also actively involved in lipid and energy homeostasis, with epicardial adipose tissue having a greater capacity for release and uptake of free fatty acids. However, there is a scarcity of knowledge on the influence of plasma lipids on EAT volume.AimThe focus of this study is on the identification of novel lipidomic species associated with CMRI-derived measures of epicardial fat in Mexican American individuals.MethodsWe performed lipidomic profiling on 200 Mexican American individuals. High-throughput mass spectrometry enabled rapid capture of precise lipidomic profiles, providing measures of 799 unique species from circulating plasma samples. Because of our extended pedigree design, we utilized a standard quantitative genetic linear mixed model analysis to determine whether lipids were correlated with EAT by formally testing for association between each lipid species and the CMRI epicardial fat phenotype.ResultsAfter correction for multiple testing using the FDR approach, we identified 135 lipid species showing significant association with epicardial fat. Of those, 131 lipid species were positively correlated with EAT, where increased circulating lipid levels were correlated with increased epicardial fat. Interestingly, the top 10 lipid species associated with an increased epicardial fat volume were from the deoxyceramide (Cer(m)) and triacylglycerol (TG) families. Deoxyceramides are atypical and neurotoxic sphingolipids. Triacylglycerols are an abundant lipid class and comprise the bulk of storage fat in tissues. Pathologically elevated TG and Cer(m) levels are related to CVD risk and, in our study, to EAT volume.ConclusionOur results indicate that specific lipid abnormalities such as enriched saturated triacylglycerols and the presence of toxic ceramides Cer(m) in plasma of our individuals could precede CVD with increased EAT volume.

The immunosuppressive landscape of the NOTCH gene family in hepatocellular carcinoma (HCC).

e16139 Background: Despite the recent addition of atezolizumab to advanced HCC first-line treatment, response biomarkers are not well studied. The involvement of the NOTCH gene family in HCC tumorigenesis has been previously discussed, yet insights on its effect on the immune microenvironment are still lacking. Methods: We systematically analyzed differentially expressed genes (DEGs) in the KEGG NOTCH pathway across HCC transcriptomics datasets from the HCCDB platform. Immune and prognostic analyses were done using The Cancer Genomic Atlas (TCGA) HCC cohort (n = 372). The TIMER 2.0 tool was used to assess immune infiltration. cBioportal was used for tumor mutational burden (TMB) and microsatellite instability (MSI) correlations. The TIDE tool assessed T cell dysfunction and DEGs efficacy predictive value using the only trial administering atezolizumab (IMvigor210, n = 348). Results: Four DEGs were identified: NCSTN, APH1A, NOTCH3, HDAC2. All four genes were significantly directly associated (spearman’s ρ &gt; 0.1, P &lt; 0.05) with immunosuppressive cells: Tregs, macrophage M2 cells, cancer-associated fibroblasts (CAF), and myeloid-derived suppressor cells (MDSC). HDAC2 was associated with higher T cell dysfunction (z score = 2.07, P = 0.04). High NOTCH3 and low HDAC2 expression served as favorable overall survival (OS) prognostic markers (HR: 0.66, 95% CI: 0.48 - 0.90, P = 0.008 &amp; HR: 1.52, 95% CI: 1.12–2.07, P = 0.006, respectively). Stratification based on the expression of these two genes and strongly associated immunosuppressive cells’ infiltration levels (ρ &gt; 0.5), revealed two unique patients’ subsets with worse OS marked by “low NOTCH3 expression with high CAF levels” and “high HDAC2 expression with high MDSC levels”. Regarding immune checkpoint genes expression, NOTCH3 and HDAC2 expression levels were directly correlated with CTLA-4, PD-1, and TIM-3, whereas NCSTN and APH1A were inversely related with PD-L1, LAG-3, and TIM-3 after correction for multiple hypothesis testing (ρ &gt; 0.2, Q value &lt; 0.05). TMB count was inversely associated with NOTCH3 expression (ρ = - 0.2, P &lt; 0.001), as for the MSI sensor score, NOTCH3 (ρ = -0.29) and APH1A (ρ = 0.29) expression had inverse and direct significant associations, respectively (P &lt; 0.0001). Exploratory subgroup analysis from the IMvigor210 trial on metastatic urothelial carcinoma patients on atezolizumab showed a significant difference in OS favoring low NOTCH3 expression (P = 0.003) and high APH1A expression (P = 0.049). Conclusions: DEGs from the NOTCH family seem to impose an immunosuppressive effect on HCC’s microenvironment. High NOTCH3 and low HDAC2 expression were identified as potential favorable prognostic markers. Interestingly, high NOTCH3 expression translated into worse OS in patients on anti-PD-L1 which could be owed to the inverse relation with TMB and MSI described in our study, thus deserving further translational investigations.

Psychiatric manifestations of rare variation in medically actionable genes: a PheWAS approach

BackgroundAs genomic sequencing moves closer to clinical implementation, there has been an increasing acceptance of returning incidental findings to research participants and patients for mutations in highly penetrant, medically actionable genes. A curated list of genes has been recommended by the American College of Medical Genetics and Genomics (ACMG) for return of incidental findings. However, the pleiotropic effects of these genes are not fully known. Such effects could complicate genetic counseling when returning incidental findings. In particular, there has been no systematic evaluation of psychiatric manifestations associated with rare variation in these genes.ResultsHere, we leveraged a targeted sequence panel and real-world electronic health records from the eMERGE network to assess the burden of rare variation in the ACMG-56 genes and two psychiatric-associated genes (CACNA1C and TCF4) across common mental health conditions in 15,181 individuals of European descent. As a positive control, we showed that this approach replicated the established association between rare mutations in LDLR and hypercholesterolemia with no visible inflation from population stratification. However, we did not identify any genes significantly enriched with rare deleterious variants that confer risk for common psychiatric disorders after correction for multiple testing. Suggestive associations were observed between depression and rare coding variation in PTEN (P = 1.5 × 10–4), LDLR (P = 3.6 × 10–4), and CACNA1S (P = 5.8 × 10–4). We also observed nominal associations between rare variants in KCNQ1 and substance use disorders (P = 2.4 × 10–4), and APOB and tobacco use disorder (P = 1.1 × 10–3).ConclusionsOur results do not support an association between psychiatric disorders and incidental findings in medically actionable gene mutations, but power was limited with the available sample sizes. Given the phenotypic and genetic complexity of psychiatric phenotypes, future work will require a much larger sequencing dataset to determine whether incidental findings in these genes have implications for risk of psychopathology.

MO657: Low Incidence of Intradialytic Hypotension During Online Post-Dilution High-Volume Haemodiafiltration: A Randomized Cross-Over Trial between Four Intermittent Dialysis Modalities

Abstract BACKGROUND AND AIMS Compared with standard haemodialysis (S-HD), online post-dilution haemodiafiltration (HDF) is associated with improved survival, especially when high convection volumes [high-volume (HV)-HDF] are achieved [1]. A superior intradialytic haemodynamic stability may play an important role in this respect. Therefore, we assessed whether the intradialytic haemodynamic profile differs between four dialysis modalities, including S-HD and HV-HDF. METHOD In the current randomized cross-over trial (NCT03249532, ClinicalTrials.gov), 40 prevalent dialysis patients were subjected to S-HD [dialysate temperature (Td) 36.5°C], HD with cool dialysate (C-HD; Td 35.5°C), low-volume (LV)-HDF [convection volume (CV) 15 L/1.73 m2/session) and HV-HDF (CV ≥23 L/1.73 m2/session) (both Td 36.5°C). Blood pressure (BP) was measured 4x/hour. The primary endpoint was the total number of intradialytic hypotensive (IDH) episodes. IDH was defined as a nadir in systolic BP (SBP) &amp;lt;90 mmHg for a pre-dialysis SBP &amp;lt;160 mmHg and &amp;lt;100 mmHg for a pre-dialysis SBP ≥160 mmHg, independent of symptoms and interventions. In addition, an explorative analysis was performed on the incidence of early-onset IDH, which has recently been related to mortality [2]. Secondary endpoints included the intradialytic courses of SBP, diastolic BP (DBP) and mean arterial pressure (MAP). RESULTS IDH occurred significantly less frequent during C-HD (0.21 episodes/session) and HV-HDF (0.27/session) compared with S-HD (0.68/session, both P &amp;lt; .0005) (Figure 1). Furthermore, early-onset of IDH was also observed more frequently during S-HD (0.32/session) than during C-HD (0.07/session, P&amp;lt;.0005) or HV-HDF (0.10/session, P = .001) (Figure 1). After correction for multiple testing, the intradialytic courses of SBP, DBP and MAP declined only significantly during S-HD (−6.8, −5.2, −5.2 mmHg/session; P = .004, &amp;lt;.0005, .002 resp.) whereas these remained stable in the other modalities (Table 1). CONCLUSION In conclusion, during both C-HD and HV-HDF, IDH occurred least frequent and the intradialytic haemodynamic stability was best preserved. In contrast, intradialytic haemodynamic stability is most dysregulated during S-HD. Therefore, it is conceivable that the survival benefit of HV-HDF over S-HD is (at least partly) due to a more stable intradialytic haemodynamic profile and consequently less repetitive tissue injury.

Poverty, Income Inequality and Economic Growth in Nigeria (1981-2019)

This study empirically examined the relationship between poverty, income inequality and economic growth in Nigeria. The study used time series data from National Bureau of Statistics (NBS) and Central Bank of Nigeria (CBN) Statistical Bulletin between the periods from 1981 to 2019. The study employed the use of Augmented Dickey Fuller test, Co integration test and Error Correction technique. The unit root test results indicated that all the variables were stationary at first difference and co-integration test confirmed a long run relationship among the variables. The error correction model shows that about 96 percent of the discrepancy between the actual and the equilibrium value of economic growth is corrected or eliminated each year. The coefficient of determination (R2) is 0.68 which shows that about 68 percent variations in the economic growth were explained by the independent variables. Furthermore, the Breusch-Godfrey Serial Correlation LM Test shows that the probability of the chi-square (2) is 0.2775 and this is greater than 0.05 at 5% significance level. This therefore confirms the absence of serial correlation. Also, the Breusch-Pagan-Godfrey Heteroscadaticity test indicates that the probability of chi-square (5) is 0.1242 and this is greater than 0.05 at 5% significant level. This also confirms the absence of heteroscedasticity in the model. From the study, the findings revealed that income inequality has a negative relationship with economic growth in the country while poverty was found to be positively related to economic growth. Similarly, the findings also revealed that poverty and income inequality has an insignificant effect on economic growth in Nigeria. Based on the findings, it can be concluded that poverty and income inequality has not significant relationship with economic growth in Nigeria. Thus, the study concludes that there is need for government of the country to come up with an all-inclusive policy and programme that will be targeted to the poor and give them ample opportunities to improve their welfare.

Depressive disorders are associated with increased peripheral blood cell deformability: a cross-sectional case-control study (Mood-Morph)

Pathophysiological landmarks of depressive disorders are chronic low-grade inflammation and elevated glucocorticoid output. Both can potentially interfere with cytoskeleton organization, cell membrane bending and cell function, suggesting altered cell morpho-rheological properties like cell deformability and other cell mechanical features in depressive disorders. We performed a cross-sectional case-control study using the image-based morpho-rheological characterization of unmanipulated blood samples facilitating real-time deformability cytometry (RT-DC). Sixty-nine pre-screened individuals at high risk for depressive disorders and 70 matched healthy controls were included and clinically evaluated by Composite International Diagnostic Interview leading to lifetime and 12-month diagnoses. Facilitating deep learning on blood cell images, major blood cell types were classified and morpho-rheological parameters such as cell size and cell deformability of every individual cell was quantified. We found peripheral blood cells to be more deformable in patients with depressive disorders compared to controls, while cell size was not affected. Lifetime persistent depressive disorder was associated with increased cell deformability in monocytes and neutrophils, while in 12-month persistent depressive disorder erythrocytes deformed more. Lymphocytes were more deformable in 12-month major depressive disorder, while for lifetime major depressive disorder no differences could be identified. After correction for multiple testing, only associations for lifetime persistent depressive disorder remained significant. This is the first study analyzing morpho-rheological properties of entire blood cells and highlighting depressive disorders and in particular persistent depressive disorders to be associated with increased blood cell deformability. While all major blood cells tend to be more deformable, lymphocytes, monocytes, and neutrophils are mostly affected. This indicates that immune cell mechanical changes occur in depressive disorders, which might be predictive of persistent immune response.

Differential Expression of MicroRNAs in Dark-Cutting Meat from Beef Carcasses

“Dark-cutting” meat in beef carcasses can result from conditions such as long-term stress and depleted glycogen stores, but some aspects of the physiological mechanisms that cause dark-cutting phenotypes remain poorly understood. Certain responses to stress factors in fully developed tissues are known to be regulated by specific microRNAs. We investigated microRNA expression in Longissimus lumborum biopsies from carcasses derived from a contemporary group of 78 steers from which a high incidence of dark-cutting meat occurred. Our objective was to identify any potential microRNA signatures that reflect the impact of environmental factors and stresses on genetic signaling networks and result in dark-cutting beef (also known as dark, firm, and dry, or DFD) in some animals. MicroRNA expression was quantified by Illumina NextSeq small RNA sequencing. When RNA extracts from DFD muscle biopsy samples were compared with normal, non-DFD (NON) samples, 29 differentially expressed microRNAs were identified in which expression was at least 20% different in the DFD samples (DFD/NON fold ratio ≤0.8 or ≥1.2). When correction for multiple testing was applied, a single microRNA bta-miR-2422 was identified at a false discovery probability (FDR) of 5.4%. If FDR was relaxed to 30%, additional microRNAs were differentially expressed (bta-miR-10174-5p, bta-miR-1260b, bta-miR-144, bta-miR-142-5p, bta-miR-2285at, bta-miR-2285e, bta-miR-3613a). These microRNAs may play a role in regulating aspects of stress responses that ultimately result in dark-cutting beef carcasses.

CT assessment of the height of the coronary arteries orifice location and the height of the aortic sinuses in women with structural changes in the coronary arteries

The most common form of cardiovascular disease in Ukraine is coronary heart disease, which is characterized by damage to the coronary arteries. The height of the aortic sinuses and the height of the coronary arteries are assessed when planning interventional procedures and cardiac surgery. Computed tomography can verify structural changes in the coronary arteries and morphometrically evaluate the components of the aortic sac. The purpose of the study: to measure the height of the coronary arteries orifice; height of the aortic sinuses in women with structural changes of the coronary arteries using computed tomography and assess the interdependence of measurements with anthropometric indicators (age, height, weight, body mass index, body surface area). Computed tomography-angiography of the chest of females with coronary arteries were processed. Statistical analysis: Shapiro-Francia test (correctness of distribution), Student’s t-test (comparison of the height of the coronary arteries and the height of the aortic sinuses); Pearson’s linear correlation; Fisher’s multifactorial regression analysis. The study found a direct correlation between height and measurability in women with coronary artery disease. The value of the growth rate was directly correlated with the height of the right aortic sinus (r=0.85, p=0.001), with the height of the lower edge of the right coronary artery orifice (r=0.74, p=0.01), the height of the upper edge of the left coronary artery orifice (r=0.67, p=0.03), the height of the upper edge of the right coronary artery orifice (r=0.67, p=0.03). It is proved that with increasing body surface area, the parameters of the right aortic sinus decrease: the inverse strong correlation r=-0.83, p=0.002. Significant direct relationships have been established between most of the measured components of the aortic root. Multifactor regression analysis showed a proven strong effect of anthropometric data and age on the height of the right aortic sinus: R=0.96, at p=0.009 (according to Fisher). This made it possible to build a model for predicting the height of the right aortic sinus depending on anthropometric and age parameters. Thus, in women with structural lesions of the coronary arteries, the increase in height correlates with an increase in the height of the right aortic sinus, the height of the coronary arteries orifice. An increase in body surface area correlates with a decrease in the height of the right aortic sinus in women with structural lesions of the coronary arteries.

Clouding Up Cognition? Secondhand Cannabis and Tobacco Exposure Related to Cognitive Functioning in Youth

BackgroundIncreasing legalization of cannabis, in addition to longstanding rates of tobacco use, raises concerns for possible cognitive decrements from secondhand smoke or environmental exposure, although little research exists. We investigate the relation between cognition and secondhand and environmental cannabis and tobacco exposure in youth. MethodsThe Adolescent Brain Cognitive Development (ABCD) Study year 2 follow-up (N = 5580; 48% female) cognitive performance and secondhand or environmental cannabis or tobacco exposure data were used. Principal components analysis identified a global cognition factor. Linear mixed-effects models assessed global cognition and individual cognitive task performance by cannabis and/or tobacco environmental exposure. Sociodemographics and other potential confounds were examined. p values were adjusted using the false discovery rate method. ResultsGlobal cognition was not related to any exposure group after testing corrections and considering confounds. Beyond covariates and family- and site-level factors, secondhand tobacco was related to poorer visual memory (p = .02), and environmental tobacco was associated with poorer visuospatial (p = .02) and language (p = .008) skills. Secondhand cannabis was related to cognition, but not after controlling for potential confounders (p > .05). Environmental cannabis was related to better oral reading (p = .01). Including covariates attenuated effect sizes. ConclusionsSecondhand tobacco exposure was associated with poorer visual memory, while environmental tobacco exposure was related to poorer language and visuospatial skills. Secondhand cannabis was not related to cognition after controlling for sociodemographic factors, but environmental cannabis exposure was related to better reading. Because, to our knowledge, this is the first known study of its kind and thus preliminary, secondhand cannabis should continue to be investigated to confirm results.

Detecting Selection in the HIV-1 Genome during Sexual Transmission Events.

Little is known about whether and how variation in the HIV-1 genome affects its transmissibility. Assessing which genomic features of HIV-1 are under positive or negative selection during transmission is challenging, because very few virus particles are typically transmitted, and random genetic drift can dilute genetic signals in the recipient virus population. We analyzed 30 transmitter–recipient pairs from the Zurich Primary HIV Infection Study and the Swiss HIV Cohort Study using near full-length HIV-1 genomes. We developed a new statistical test to detect selection during transmission, called Selection Test in Transmission (SeTesT), based on comparing the transmitter and recipient virus population and accounting for the transmission bottleneck. We performed extensive simulations and found that sensitivity of detecting selection during transmission is limited by the strong population bottleneck of few transmitted virions. When pooling individual test results across patients, we found two candidate HIV-1 genomic features for affecting transmission, namely amino acid positions 3 and 18 of Vpu, which were significant before but not after correction for multiple testing. In summary, SeTesT provides a general framework for detecting selection based on genomic sequencing data of transmitted viruses. Our study shows that a higher number of transmitter–recipient pairs is required to improve sensitivity of detecting selection.

Single-Nucleotide Polymorphisms in LEP and LEPR Associated With Breast Cancer Risk: Results From a Multicenter Case-Control Study in Chinese Females.

BackgroundLeptin (LEP) plays a physiological role through its specific receptor (LEPR) and is involved in the occurrence and development of breast cancer. Our current study aimed at determining the influence of single-nucleotide polymorphisms (SNPs) in the genes coding for LEP and LEPR on breast cancer risk.MethodsIn the present study, 963 breast cancer cases and 953 controls were enrolled. Five SNPs of LEP and two of LEPR were chosen to evaluate the correlation of selected SNPs with breast cancer susceptibility among women in northern and eastern China. Analyses were further stratified by body mass index (BMI), waist–hip rate (WHR), estrogen receptor, and progesterone receptor status. The expression patterns of risk variant-associated genes were detected by expression quantitative trait locus (eQTL) analysis with eQTLGen and The Cancer Genome Atlas database.ResultsThere were significant differences between breast cancer cases and control groups in the menopausal status and family history of breast cancer. Two SNPs (rs1137101 and rs4655555) of the LEPR gene decreased overall breast cancer risk, and other five SNPs showed no significant association with breast cancer risk. rs1137101 (GA vs. GG; adjusted OR = 0.719, 95% CI = 0.578–0.894, p = 0.003) and rs4655555 (TT vs. AA; adjusted OR = 0.574, 95% CI = 0.377–0.873, p = 0.009) significantly decreased breast cancer risk after Bonferroni correction for multiple testing. In subgroup analyses, the GA and GA + AA genotypes of LEPR rs1137101 associated with decreased breast cancer risk in the subgroup of BMI ≤ 24 kg/m2 or WHR ≥ 0.85 after Bonferroni correction. Furthermore, we found that the expressions of rs4655555-associated gene LEPR and leptin receptor overlapping transcript (LEPROT) were upregulated in breast cancer tumor tissues compared with adjacent normal tissues, and a higher expression of LEPR in tumor tissues was correlated with poor prognosis of breast cancer patients using The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data.ConclusionOur study demonstrated that the polymorphisms rs1137101 and rs4655555 located in the LEPR gene decreased breast cancer risk in Chinese females, which might be a research-worthy bio-diagnostic marker and applied for early prediction and risk assessment of breast cancer.

Obstetrical mode of delivery and behavioural outcomes in childhood and adolescence: findings from the Millennium Cohort Study

PurposeTo examine the association between mode of delivery (in particular caesarean section) and behavioural outcomes in offspring at six time-points between age 3 and 17 years.MethodsSimilar to previous work examining the association between mode of delivery and behavioural outcomes in offspring at age 7, we used maternal-reported data from the Millennium Cohort Study. Data on mode of delivery were collected when children were 9 months and categorised as spontaneous vaginal delivery, assisted vaginal delivery, induced vaginal delivery, emergency caesarean section, planned caesarean section and caesarean section after induction of labor. Data on behavioural outcomes were collected at ages 3, 5, 7, 11, 14 and 17 years using the Strengths and Difficulties Questionnaire (SDQ). Crude and adjusted logistic regression examined mode of delivery–behavioural difficulties relationship, using validated SDQ cut-off points (total SDQ ≥ 17, emotional ≥ 5, conduct ≥ 4, hyperactivity ≥ 7, peer problems ≥ 4 and prosocial behaviour ≤ 4). Multilevel models with linear splines examined the association between mode of delivery and repeated measures of SDQ.ResultsThere were 18,213 singleton mother–child pairs included at baseline, 13,600 at age 3; 13,831 at age 5; 12,687 at age 7; 11,055 at age 11; 10,745 at age 14 and 8839 at age 17. Adjusted logistic regression suggested few associations between mode of delivery and behavioural outcomes at ages 3, 5, 11, 14 and 17 years using validated SDQ cut-off points. After correction for multiple testing, only the protective association between planned caesarean section-Conduct difficulties at age 5 years (OR 0.63, 95% CI 0.46, 0.85) and positive association between caesarean section after induction-Emotional difficulties at age 11 years (OR 1.57, 95% CI 1.19, 2.07) remained statistically significant. Multilevel modelling suggested mean SDQ scores were similar in each mode of delivery group at each time point.ConclusionsResults of this study indicate that mode of delivery is unlikely to have a major impact on behavioural outcomes.

Relationships between Racket Arm Joint Moments and Racket Head Speed during the Badminton Jump Smash Performed by Elite Male Malaysian Players

Three-dimensional position data of nineteen elite male Malaysian badminton players performing a series of maximal jump smashes were collected using a motion capture system. A ‘resultant moments’ inverse dynamics analysis was performed on the racket arm joints (shoulder, elbow and wrist). Relationships between racket head speed and peak joint moments were quantified using correlational analyses, inclusive of a Benjamini–Hochberg correction for multiple-hypothesis testing. The racket head centre speed at racket–shuttlecock contact was, on average, 61.2 m/s with a peak of 68.5 m/s which equated to average shuttlecock speeds of 95.2 m/s with a peak of 105.0 m/s. The correlational analysis revealed that a larger shoulder internal rotation moment (r = 0.737), backwards shoulder plane of elevation moment (r = 0.614) and wrist extension moment (r = −0.564) were associated with greater racket head centre speed at racket–shuttlecock contact. Coaches should consider strengthening the musculature associated with shoulder internal rotation, plane of elevation and wrist extension. This work provides a unique analysis of the joint moments of the racket arm during the badminton jump smash performed by an elite population and highlights significant relationships between racket head speed and peak resultant joint moments.