Adolescent and young adult (AYA) patients with cancer are a group with underexplored needs throughout treatment and in survivorship. This missing knowledge can influence their quality of life (QoL). Given this fact, we have developed a smartphone app based on a cocreation process and have an investigation of QoL among users planned as part of pilot testing this app. Future research is warranted to determine the effect of mobile health (mHealth) tools such as smartphone apps among the AYA cancer population.

Genome-wide association studies (GWAS) have consistently identified an association between coronary artery disease (CAD) and a locus on chromosome 10 containing a single gene, JCAD (formerly KIAA1462). However, little is known about the mechanism by which JCAD could influence the development of atherosclerosis.

Structure-selective endonucleases cleave branched DNA substrates. Slx1 is unique among structure-selective nucleases because it can cleave all branched DNA structures at multiple sites near the branch point. The mechanism behind this broad range of activity is unknown. The present study structurally and biochemically investigated fungal Slx1 to define a new protein interface that binds the non-cleaved arm of branched DNAs. The DNA arm bound at this new site was positioned at a sharp angle relative to the arm that was modeled to interact with the active site, implying that Slx1 uses DNA bending to localize the branch point as a flexible discontinuity in DNA. DNA binding at the new interface promoted a disorder-order transition in a region of the protein that was located in the vicinity of the active site, potentially participating in its formation. This appears to be a safety mechanism that ensures that DNA cleavage occurs only when the new interface is occupied by the non-cleaved DNA arm. Models of Slx1 that interacted with various branched DNA substrates were prepared. These models explain the way in which Slx1 cuts DNA toward the 3' end away from the branch point and elucidate the unique ability of Slx1 to cleave various DNA structures.

Objectives mHealth interventions for MNCH have been shown to improve uptake of antenatal and neonatal services in low- and middle-income countries (LMICs). However, little systematic analysis is available about their impact on infant health outcomes, such as reducing low birth weight or malnutrition among children under the age of five. The objective of this study is to determine if an age- and stage-based mobile phone voice messaging initiative for women, during pregnancy and up to 1 year after delivery, can reduce low birth weight and child malnutrition and improve women's infant care knowledge and practices. Methods We conducted a pseudo-randomized controlled trial among pregnant women from urban slums and low-income areas in Mumbai, India. Pregnant women, 18 years and older, speaking Hindi or Marathi were enrolled and assigned to receive mMitra messages (intervention group N = 1516) or not (Control group N = 500). Women in the intervention group received mMitra voice messages two times per week throughout their pregnancy and until their infant turned 1 year of age. Infant's birth weight, anthropometric data at 1 year of age, and status of immunization were obtained from Maternal Child Health (MCH) cards to assess impact on primary infant health outcomes. Women's infant health care practices and knowledge were assessed through interviews administered immediately after women enrolled in the study (Time 1), after they delivered their babies (Time 2), and after their babies turned 1 year old (Time 3). 15 infant care practices self-reported by women (Time 3) and knowledge on ten infant care topics (Time 2) were also compared between intervention and control arms. Results We observed a trend for increased odds of a baby being born at or above the ideal birth weight of 2.5 kg in the intervention group compared to controls (odds ratio (OR) 1.334, 95% confidence interval (CI) 0.983-1.839, p = 0.064). The intervention group performed significantly better on two infant care practice indicators: giving the infant supplementary feeding at 6 months of age (OR 1.4, 95% CI 1.08-1.82, p = 0.009) and fully immunizing the infant as prescribed under the Government of India's child immunization program (OR 1.531, 95% CI 1.141-2.055, p = 0.005). Women in the intervention group had increased odds of knowing that the baby should be given solid food by 6 months (OR 1.89, 95% CI 1.371-2.605, p < 0.01), that the baby needs to be given vaccines (OR 1.567, 95% CI 1.047-2.345, p = 0.028), and that the ideal birth weight is > 2.5 kg (OR 2.279, 95% CI 1.617-3.213, p < 0.01). Conclusions for Practice This study provides robust evidence that tailored mobile voice messages can significantly improve infant care practices and maternal knowledge that can positively impact infant child health. Furthermore, this is the first prospective study of a voice-based mHealth intervention to demonstrate a positive impact on infant birth weight, a health outcome of public health importance in many LMICs.

The molecular basis of cell-cell adhesion in woody tissues is not known. Xylem cells in wood particles of hybrid poplar (Populus tremula × P. alba cv. INRA 717-1B4) were separated by oxidation of lignin with acidic sodium chlorite when combined with extraction of xylan and rhamnogalacturonan-I (RG-I) using either dilute alkali or a combination of xylanase and RG-lyase. Acidic chlorite followed by dilute alkali treatment enables cell-cell separation by removing material from the compound middle lamellae between the primary walls. Although lignin is known to contribute to adhesion between wood cells, we found that removing lignin is a necessary but not sufficient condition to effect complete cell-cell separation in poplar lines with various ratios of syringyl:guaiacyl lignin. Transgenic poplar lines expressing an Arabidopsis thaliana gene encoding an RG-lyase (AtRGIL6) showed enhanced cell-cell separation, increased accessibility of cellulose and xylan to hydrolytic enzyme activities, and increased fragmentation of intact wood particles into small cell clusters and single cells under mechanical stress. Our results indicate a novel function for RG-I, and also for xylan, as determinants of cell-cell adhesion in poplar wood cell walls. Genetic control of RG-I content provides a new strategy to increase catalyst accessibility and saccharification yields from woody biomass for biofuels and industrial chemicals.

Among tetrapods, only salamanders can regenerate their limbs and tails throughout life. This amazing regenerative ability has attracted the attention of scientists for hundreds of years. Now that large, salamander genomes are beginning to be sequenced for the first time, omics tools and approaches can be used to integrate new perspectives into the study of tissue regeneration. Here we argue the need to move beyond the primary salamander models to investigate regeneration in other species. Salamanders at first glance come across as a phylogenetically conservative group that has not diverged greatly from their ancestors. While salamanders do present ancestral characteristics of basal tetrapods, including the ability to regenerate limbs, data from fossils and data from studies that have tested for species differences suggest there may be considerable variation in how salamanders develop and regenerate their limbs. We review the case for expanded studies of salamander tissue regeneration and identify questions and approaches that are most likely to reveal commonalities and differences in regeneration among species. We also address challenges that confront such an initiative, some of which are regulatory and not scientific. The time is right to gain evolutionary perspective about mechanisms of tissue regeneration from comparative studies of salamander species.

Patients with chronic kidney disease (CKD) bear a substantial burden of comorbidities leading to the prescription of multiple drugs and a risk of polypharmacy. However, data on medication use in this population are scarce.

Graph embedding learning that aims to automatically learn low-dimensional node representations, has drawn increasing attention in recent years. To date, most recent graph embedding methods are evaluated on social and information networks and are not comprehensively studied on biomedical networks under systematic experiments and analyses. On the other hand, for a variety of biomedical network analysis tasks, traditional techniques such as matrix factorization (which can be seen as a type of graph embedding methods) have shown promising results, and hence there is a need to systematically evaluate the more recent graph embedding methods (e.g. random walk-based and neural network-based) in terms of their usability and potential to further the state-of-the-art.

The conclusions from the multiple randomized clinical trials exploring the relationship between development of intussusception and rotavirus vaccination among neonates and infants have been controversial.

Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B.

Introduction: Leptin is a hormone secreted by adipocytes that has been associated with the epithelial-mesenchymal transition (EMT). Additionally, leptin promotes the migration and invasion of mammary epithelial cells through the activation of FAK and Src kinases, which are part of a regulatory complex of signaling pathways that promotes the expression of proteins related to the formation of proteolytic structures involved in the invasion and progression of cancer. Recently, overexpression and activation of Hic-5 during the EMT have been shown to induce the formation of actin puncta; these structures are indicative of the formation and functionality of invadopodia, which promote the local degradation of extracellular matrix components and cancer metastasis. Objective: To evaluate the role of FAK and Src kinases in the expression of Hic-5 during the epithelial-mesenchymal transition induced by leptin in MCF10A cells. Materials and methods: We used specific inhibitors of FAK (PF-573228) and Src (PP2) to evaluate Hic-5 expression and subcellular localization by Western blot and immunofluorescence assays and to investigate the formation of actin puncta by epifluorescence in MCF10A cells stimulated with leptin. Results: Leptin induced an increase in Hic-5 expression and the formation of actin puncta. Pretreatment with inhibitors of FAK (PF-573228) and Src (PP2) promoted a decrease in Hic-5 expression and actin puncta formation in the non-tumorigenic mammary epithelial cell line MCF10A. Conclusion: In MCF10A cells, leptin-induced Hic-5 expression and perinuclear localization, as well as the formation of actin puncta through a mechanism dependent on the kinase activity of FAK and Src.

We investigated the role of the competing endogenous RNA (ceRNA) network in the development and progression of pancreatic adenocarcinoma (PAAD). We analyzed the expression profiles of PAAD and normal pancreatic tissues from multiple GEO databases and identified 457 differentially expressed circular RNAs (DEcircRNAs), 19 microRNAs (DEmiRNAs) and 1993 mRNAs (DEmRNAs). We constructed a ceRNA network consisting of 4 DEcircRNAs, 3 DEmiRNAs and 149 DEmRNAs that regulates the NF-kappa B, PI3K-Akt, and Wnt signaling pathways. We then identified and validated five hub genes, CXCR4, HIF1A, ZEB1, SDC1 and TWIST1, which are overexpressed in PAAD tissues. The expression of CXCR4, HIF1A, ZEB1, and SDC1 in PAAD was regulated by circ-UBAP2 and hsa-miR-494. The expression of CXCR4 and ZEB1 correlated with the levels of M2 macrophages, T-regulatory cells (Tregs) and exhausted T cells in the PAAD tissues. The expression of CXCR4 and ZEB1 positively correlated with the expression of CTLA-4 and PD-1. This suggests that CXCR4 and ZEB1 proteins inhibit antigen presentation and promote immune escape mechanisms in PAAD cells. In summary, our data suggest that the circUBAP2-mediated ceRNA network modulates PAAD by regulating the infiltration and function of immune cells.

This study aims to explore the expression and degree of methylation of lncRNA MEG3 in gastric cancer tissues and to analyze its effect on the migration and proliferation of gastric cancer patients and the mechanism by which this occurs. The targeting relationship between MEG3, miR-181a-5p and ATP4B was detected through molecular biology experiments. Wound healing, transwell, colony formation and flow cytometry assays were used to analyze the effects of lncRNA MEG3 and methylation on tumor cell migration, invasion, proliferation and apoptosis. In addition, a tumor xenotransplantation model was established to study the influence of MEG3 on tumor growth in vivo. Bioinformatics analysis showed that lncRNA MEG3 and ATP4B were downregulated in gastric cancer tissues compared with normal tissues. Bioinformatics predicted that ATP4B might be regulated by targeting miR-181a-5p. The overexpression of MEG3 and the application of 5-Aza treatment inhibited the migration, invasion and proliferation of MGC-803 cells and promoted apoptosis. In gastric cancer tissues, MEG3 is hypermethylated to decrease expression. Once the expression of MEG3 is restored or methylation is inhibited, tumor growth can be inhibited both in vivo and in vitro. This finding could be utilized as a clinical reference for gastric cancer treatment in the future.

Motor cortical beta activity (13-30 Hz) is a hallmark signature of healthy and pathological movement, but its behavioural relevance remains unclear. Using high-precision magnetoencephalography (MEG), we show that during the classical event-related desynchronisation (ERD) and event-related synchronisation (ERS) periods, motor cortical beta activity in individual trials (n > 12,000) is dominated by high amplitude, transient, and infrequent bursts. Beta burst probability closely matched the trial-averaged beta amplitude in both the pre- and post-movement periods, but individual bursts were spatially more focal than the classical ERS peak. Furthermore, prior to movement (ERD period), beta burst timing was related to the degree of motor preparation, with later bursts resulting in delayed response times. Following movement (ERS period), the first beta burst was delayed by approximately 100 milliseconds when an incorrect response was made. Overall, beta burst timing was a stronger predictor of single trial behaviour than beta burst rate or single trial beta amplitude. This transient nature of motor cortical beta provides new constraints for theories of its role in information processing within and across cortical circuits, and its functional relevance for behaviour in both healthy and pathological movement.

Replication stress poses a serious threat to genome stability. Recombination-Dependent-Replication (RDR) promotes DNA synthesis resumption from arrested forks. Despite the identification of chromatin restoration pathways after DNA repair, crosstalk coupling RDR and chromatin assembly is largely unexplored. The fission yeast Chromatin Assembly Factor-1, CAF-1, is known to promote RDR. Here, we addressed the contribution of histone deposition to RDR. We expressed a mutated histone, H3-H113D, to genetically alter replication-dependent chromatin assembly by destabilizing (H3-H4)2 tetramer. We established that DNA synthesis-dependent histone deposition, by CAF-1 and Asf1, promotes RDR by preventing Rqh1-mediated disassembly of joint-molecules. The recombination factor Rad52 promotes CAF-1 binding to sites of recombination-dependent DNA synthesis, indicating that histone deposition occurs downstream Rad52. Histone deposition and Rqh1 activity act synergistically to promote cell resistance to camptothecin, a topoisomerase I inhibitor that induces replication stress. Moreover, histone deposition favors non conservative recombination events occurring spontaneously in the absence of Rqh1, indicating that the stabilization of joint-molecules by histone deposition also occurs independently of Rqh1 activity. These results indicate that histone deposition plays an active role in promoting RDR, a benefit counterbalanced by stabilizing at-risk joint-molecules for genome stability.

Propofol causes a profound inhibition of fatty acid oxidation and reduces spare electron transfer chain capacity in a range of human and rodent cells and tissues-a feature that might be related to the pathogenesis of Propofol Infusion Syndrome. We aimed to explore the mechanism of propofol-induced alteration of bioenergetic pathways by describing its kinetic characteristics.

The processes that result in progression of idiopathic pulmonary fibrosis (IPF) remain enigmatic. Moreover, the course of this disease can be highly variable and difficult to accurately predict. We hypothesized analyses of body mass index (BMI), a simple, routine clinical measure, may also have prognostic value in these patients, and might provide mechanistic insights. We investigated the associations of BMI changes with outcome, plasma adipokines, and adaptive immune activation among IPF patients.

In recent years, several high-dimensional, accurate, and effective classification methods have been proposed for the automatic discrimination of the subject between Alzheimer's disease (AD) or its prodromal phase {i.e., mild cognitive impairment (MCI)} and healthy control (HC) persons based on T1-weighted structural magnetic resonance imaging (sMRI). These methods emphasis only on using the individual feature from sMRI images for the classification of AD, MCI, and HC subjects and their achieved classification accuracy is low. However, latest multimodal studies have shown that combining multiple features from different sMRI analysis techniques can improve the classification accuracy for these types of subjects. In this paper, we propose a novel classification technique that precisely distinguishes individuals with AD, aAD (stable MCI, who had not converted to AD within a 36-month time period), and mAD (MCI caused by AD, who had converted to AD within a 36-month time period) from HC individuals. The proposed method combines three different features extracted from structural MR (sMR) images using voxel-based morphometry (VBM), hippocampal volume (HV), and cortical and subcortical segmented region techniques. Three classification experiments were performed (AD vs. HC, aAD vs. mAD, and HC vs. mAD) with 326 subjects (171 elderly controls and 81 AD, 35 aAD, and 39 mAD patients). For the development and validation of the proposed classification method, we acquired the sMR images from the dataset of the National Research Center for Dementia (NRCD). A five-fold cross-validation technique was applied to find the optimal hyperparameters for the classifier, and the classification performance was compared by using three well-known classifiers: K-nearest neighbor, support vector machine, and random forest. Overall, the proposed model with the SVM classifier achieved the best performance on the NRCD dataset. For the individual feature, the VBM technique provided the best results followed by the HV technique. However, the use of combined features improved the classification accuracy and predictive power for the early classification of AD compared to the use of individual features. The most stable and reliable classification results were achieved when combining all extracted features. Additionally, to analyze the efficiency of the proposed model, we used the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset to compare the classification performance of the proposed model with those of several state-of-the-art methods.

Mechanical loading is essential for the maintenance of musculoskeletal homeostasis. Cartilage has been demonstrated to be highly mechanoresponsive, but the mechanisms by which chondrocytes respond to mechanical stimuli are not clearly understood. The goal of the study was to determine how LRP4, LRP5, and LRP6 within canonical Wnt-signaling are regulated in simulated microgravity and cyclic hydrostatic pressure, and to investigate the potential role of LRP 4/5/6 in cartilage degeneration. Rat chondrosacroma cell (RCS) pellets were stimulated using either cyclic hydrostatic pressure (1Hz, 7.5 MPa, 4hr/day) or simulated microgravity in a rotating wall vessel (RWV) bioreactor (11RPM, 24hr/day). LRP4/5/6 mRNA expression was assessed by RT-qPCR and LRP5 protein expression was determined by fluorescent immunostaining. To further evaluate our in vitro findings in vivo, mice were subjected to hindlimb suspension for 14 days and the femoral heads stained for LRP5 expression. We found that, in vitro, LRP4/5/6 mRNA expression is modulated in a time-dependent manner by mechanical stimulation. Additionally, LRP5 protein expression is upregulated in response to both simulated microgravity and cyclic hydrostatic pressure. LRP5 is also upregulated in vivo in the articular cartilage of hindlimb suspended mice. This is the first study to examine how LRP4/5/6, critical receptors within musculoskeletal biology, respond to mechanical stimulation. Further elucidation of this mechanism could provide significant clinical benefit for the identification of pharmaceutical targets for the maintenance of cartilage health.

To compare the magnetic resonance imaging (MRI) features of deep infiltrating endometriosis (DIE) lesions before and after pregnancy.