Pathway Mapping Research Articles

Multitarget mechanism of Yiqi Jiedu Huayu decoction on diabetic cardiomyopathy based on network pharmacology

IntroductionYiqi Jiedu Huayu decoction (YJHD) is a traditional Chinese medicine preparation consisting of seven herbs, which has been widely used in the treatment of diabetic cardiomyopathy (DCM) and has achieved positive treatment effects. However, due to its multicomponent, multitarget characteristics, the pharmacological mechanism of YJHD in the treatment of DCM remains unclear. MethodsThe potential mechanism of YJHD in the treatment of DCM was explored and validated using network pharmacology, molecular docking technology, and animal experiments. Compounds and targets of YJHD were obtained by the TCMSP, ETCM, and SymMap databases. Next, the targets of DCM were predicted by GeneCards and DisGeNET databases. Then, through a series of screens, the major targets of YJHD for the treatment of DCM were identified. Through GO and KEGG enrichment analysis and signaling pathway mapping, the role of major targets in the treatment of DCM was analyzed. Finally, the results were validated by molecular docking and animal experiments. Results95 active ingredients and 38 major targets were identified. Enrichment analysis indicated that YJHD may directly or indirectly regulate multiple pathways, improving myocardial glucose metabolism, inflammation, and fibrosis. The binding of active ingredients to key targets was simulated by molecular docking. In addition, animal models of DCM were established and treated with YJHD, which showed that YJHD can effectively improve the pathological changes of DCM. Furthermore, the regulatory effect of YJHD on certain key pathways were confirmed by western blotting. ConclusionThrough multicomponent and multitarget analysis, this study reveals the potential mechanisms of YJHD in DCM treatment.

Mitochondrial Disruption by Amyloid Beta 42 Identified by Proteomics and Pathway Mapping.

Alzheimer’s disease (AD) is marked by chronic neurodegeneration associated with the occurrence of plaques containing amyloid β (Aβ) proteins in various parts of the human brain. An increase in several Aβ fragments is well documented in patients with AD and anti-amyloid targeting is an emerging area of therapy. Soluble Aβ can bind to various cell surface and intracellular molecules with the pathogenic Aβ42 fragment leading to neurotoxicity. Here we examined the effect of Aβ42 on network adaptations in the proteome of nerve growth factor (NGF) differentiated PC12 cells using liquid-chromatography electrospray ionization mass spectrometry (LC-ESI MS/MS) proteomics. Whole-cell peptide mass fingerprinting was coupled to bioinformatic gene set enrichment analysis (GSEA) in order to identify differentially represented proteins and related gene ontology (GO) pathways within Aβ42 treated cells. Our results underscore a role for Aβ42 in disrupting proteome responses for signaling, bioenergetics, and morphology in mitochondria. These findings highlight the specific components of the mitochondrial response during Aβ42 neurotoxicity and suggest several new biomarkers for detection and surveillance of amyloid disease.

A Direct Comparative Study of Bronchoscopic Navigation Planning Platforms for Peripheral Lung Navigation: The ATLAS Study.

The use of mapping to guide peripheral lung navigation (PLN) represents an advance in the management of peripheral pulmonary lesions (PPL). Software has been developed to virtually reconstruct computed tomography images into 3-dimensional airway maps and generate navigation pathways to target PPL. Despite this there remain significant gaps in understanding the factors associated with navigation success and failure including the cartographic performance characteristics of these software algorithms. This study was designed to determine whether differences exist when comparing PLN mapping platforms. An observational direct comparison was performed to evaluate navigation planning software packages for the lung. The primary endpoint was distance from the terminal end of the virtual navigation pathway to the target PPL. Secondary endpoints included distal virtual and segmental airway generations built to the target and/or in each lung. Twenty-five patient chest computed tomography scans with 41 PPL were evaluated. Virtual airway and navigation pathway maps were generated for each scan/nodule across all platforms. Virtual navigation pathway comparison revealed differences in the distance from the terminal end of the navigation pathway to the target PPL (robotic bronchoscopy 9.4 mm vs. tip-tracked electromagnetic navigation 14.2 mm vs. catheter based electromagnetic navigation 17.2 mm, P=0.0005) and in the generation of complete distal airway maps. Comparing PLN planning software revealed significant differences in the generation of virtual airway and navigation maps. These differences may play an unrecognized role in the accurate PLN and biopsy of PPL. Further prospective trials are needed to quantify the effect of the differences reported.

Kinase-Catalyzed Biotinylation to Map Cell Signaling Pathways: Application to Epidermal Growth Factor Signaling.

Cell signaling involves a network of protein-protein interactions and post-translational modifications that govern cellular responses to environmental cues. To understand and ultimately modulate these signaling pathways to confront disease, the complex web of proteins that becomes phosphorylated after extracellular stimulation has been studied using mass spectrometry-based proteomics methods. To complement prior work and fully characterize all phosphorylated proteins after the stimulation of cell signaling, we developed K-BMAPS (kinase-catalyzed biotinylation to map signaling), which utilizes ATP-biotin as a kinase cosubstrate to biotin label substrates. As a first application of the K-BMAPS method, the well-characterized epidermal growth factor receptor (EGFR) kinase signaling pathway was monitored by treating epidermal growth factor (EGF)-stimulated HeLa lysates with ATP-biotin, followed by streptavidin enrichment and quantitative mass spectrometry analysis. On the basis of the dynamic phosphoproteins identified, a pathway map was developed considering functional categories and known interactors of EGFR. Remarkably, 94% of the K-BMAPS hit proteins were included in the EGFR pathway map. With many proteins involved in transcription, translation, cell adhesion, and GTPase signaling, K-BMAPS identified phosphoproteins were associated with late and continuous signaling events. In summary, the K-BMAPS method is a powerful tool to map the dynamic phosphorylation governing cell signaling pathways.

A pathway map of signaling events triggered upon SARS-CoV infection.

Severe acute respiratory syndrome coronaviruses (SARS-CoVs) caused worldwide epidemics over the past few decades. Extensive studies on various strains of coronaviruses provided a basic understanding of the pathogenesis of the disease. Presently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is leading a global pandemic with unprecedented challenges. This is the third coronavirus outbreak of this century. A signaling pathway map of signaling events induced by SARS-CoV infection is not yet available. In this study, we present a literature-annotated signaling pathway map of reactions induced by SARS-CoV infected cells. Multiple signaling modules were found to be orchestrated including PI3K-AKT, Ras-MAPK, JAK-STAT, Type 1 IFN and NFκB. The signaling pathway map of SARS-CoV consists of 110 molecules and 101 reactions mediated by SARS-CoV proteins. The pathway reaction data are available in various community standard data exchange formats including Systems Biology Graphical Notation (SBGN). The pathway map is publicly available through the GitHub repository and data in various formats can be freely downloadable.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12079-021-00642-2.

Niche differentiation of belowground microorganisms and their functional signatures in Assam type tea (Camellia sinensis var. assamica).

We employed an Illumina-based high-throughput metagenomics sequencing approach to unveil the rhizosphere and root endosphere microbial community associated with an organically grown Camellia population located at the Experimental Garden for Plantation Crops, Assam (India). The de novo assembled tea root endosphere metagenome contained 24,231 contigs (total 7,771,089 base pairs with an average length of 321 bps), while tea rhizosphere soil metagenome contained 261,965 sequences (total 230,537,174 base pairs, average length 846). The most prominent rhizobacteria belonged to the genera, viz., Bacillus (10.35%), Candidatus Solibacter (6.36%), Burkholderia (5.19%), Pseudomonas (3.9%), Streptomyces (3.52%), and Bradyrhizobium (2.77%), while the root endosphere was dominated by bacterial genera, viz., Serratia (46.64%), Methylobacterium (8.02%), Yersinia (5.97%), Burkholderia (2.05%), etc. The presence of few agronomically important bacterial genera, Bradyrhizobium, Rhizobium (each 0.93%), Sinorhizobium (0.34%), Azorhizobium, and Flavobacterium (0.17% each), was also detected in the root endosphere. KEGG pathway mapping indicated the presence of microbial metabolic pathway genes related to tyrosine metabolism, tryptophan metabolism, glyoxylate, and dicarboxylate metabolism which play important roles in endosphere activities, including survival, growth promotion, and host adaptation. The root endosphere microbiome also contained few important plant growth promoting traits related to phytohormone production, abiotic stress alleviation, mineral solubilization, and plant disease suppression.

KEGG mapping tools for uncovering hidden features in biological data.

In contrast to artificial intelligence and machine learning approaches, KEGG (https://www.kegg.jp) has relied on human intelligence to develop "models" of biological systems, especially in the form of KEGG pathway maps that are manually created by capturing knowledge from published literature. The KEGG models can then be used in biological big data analysis, for example, for uncovering systemic functions of an organism hidden in its genome sequence through the simple procedure of KEGG mapping. Here we present an updated version of KEGG Mapper, a suite of KEGG mapping tools reported previously (Kanehisa and Sato, Protein Sci 2020; 29:28-35), together with the new versions of the KEGG pathway map viewer and the BRITE hierarchy viewer. Significant enhancements have been made for BRITE mapping, where the mapping result can be examined by manipulation of hierarchical trees, such as pruning and zooming. The tree manipulation feature has also been implemented in the taxonomy mapping tool for linking KO (KEGG Orthology) groups and modules to phenotypes.

The Interdependency and Co-Regulation of the Vitamin D and Cholesterol Metabolism.

Vitamin D and cholesterol metabolism overlap significantly in the pathways that contribute to their biosynthesis. However, our understanding of their independent and co-regulation is limited. Cardiovascular disease is the leading cause of death globally and atherosclerosis, the pathology associated with elevated cholesterol, is the leading cause of cardiovascular disease. It is therefore important to understand vitamin D metabolism as a contributory factor. From the literature, we compile evidence of how these systems interact, relating the understanding of the molecular mechanisms involved to the results from observational studies. We also present the first systems biology pathway map of the joint cholesterol and vitamin D metabolisms made available using the Systems Biology Graphical Notation (SBGN) Markup Language (SBGNML). It is shown that the relationship between vitamin D supplementation, total cholesterol, and LDL-C status, and between latitude, vitamin D, and cholesterol status are consistent with our knowledge of molecular mechanisms. We also highlight the results that cannot be explained with our current knowledge of molecular mechanisms: (i) vitamin D supplementation mitigates the side-effects of statin therapy; (ii) statin therapy does not impact upon vitamin D status; and critically (iii) vitamin D supplementation does not improve cardiovascular outcomes, despite improving cardiovascular risk factors. For (iii), we present a hypothesis, based on observations in the literature, that describes how vitamin D regulates the balance between cellular and plasma cholesterol. Answering these questions will create significant opportunities for advancement in our understanding of cardiovascular health.

Identification of Key Genes Controlling Carotenoid Metabolism during Apricot Fruit Development by Integrating Metabolic Phenotypes and Gene Expression Profiles.

To explore the metabolic basis of carotenoid accumulation in different developmental periods of apricot fruits, targeted metabonomic and transcriptomic analyses were conducted in four developmental periods (S1-S4) in two cultivars (Prunus armeniaca cv. "Kuchebaixing" with white flesh and P. armeniaca cv. "Shushangganxing" with orange flesh) with different carotenoid contents. 14 types of carotenes and 27 types of carotene lipids were identified in apricot flesh in different developmental periods. In S3 and S4, the carotenoid contents of the two cultivars were significantly different, and β-carotene and (E/Z)-phytoene were the key metabolites that caused the difference in the total carotenoid content between the examined cultivars. Twenty-five structural genes (including genes in the methylerythritol 4-phosphate and carotenoid biosynthesis pathways) related to carotenoid biosynthesis were identified among the differentially expressed genes in different developmental periods of the two cultivars, and a carotenoid metabolic pathway map of apricot fruits was drawn according to the KEGG pathway map. The combined analysis of carotenoid metabolism data and transcriptome data showed that PSY, NCED1, and CCD4 were the key genes leading to the great differences in the total carotenoid content. The results provide a new approach to study the synthesis and accumulation of carotenoids in apricot fruits.

The network map of Elabela signaling pathway in physiological and pathological conditions.

Elabela (ELA; also called Apela and Toddler) is one of the recently discovered ligand among the two endogenous peptide ligands (Apelin and Elabela) of the apelin receptor (APLNR, also known as APJ). Elabela-induced signaling plays a crucial role in diverse biological processes, including formation of the embryonic cardiovascular system and early placental development by reducing the chances of occurrence of preeclampsia during pregnancy. It also plays the major role in the renoprotection by reducing kidney injury and the inflammatory response and regulation of gene expression associated with heart failure and fibrosis. Elabela may be processed into different active peptides, each of which binds to APLNR and predominantly activates the signals through PI3K/AKT pathway. Owing to its biomedical importance, we developed a consolidated signaling map of Elabela, in accordance with the NetPath criteria. The presented Elabela signaling map comprises 12 activation/inhibition events, 15 catalysis events, 1 molecular association, 34 gene regulation events and 32 protein expression events. The Elabela signaling pathway map is freely made available through the WikiPathways Database ( https://www.wikipathways.org/index.php/Pathway:WP5100 ).

Continuous Dynamic Mapping of Cranial Nerve Pathways and Long Tracts Inside the Brainstem: Useful Technique of Intraoperative Neurophysiological Monitoring

Surgery of intrinsic brainstem lesions is extremely dangerous, consequently the knowledge of anatomy and safe entry zones is extremely important. The technological progress was achieved with the widespread clinical use of intraoperative neurophysiological monitoring (IONM) which has proven to further improve the safety of operating on intrinsic brainstem lesions. The relevance of the study is conditioned by the fact that the tumor alters the normal anatomy and distorts the location of well-known landmarks and structures. In this regard, this paper is directed at identification of the placement of conductive pathways in the thickness of the brain stem and directly in the depth of the lesion (in the tumor or cavern), respectively to the surgical manipulations aimed at injury prevention. The results were achieved by a retrospective review of medical reports. The paper represents the results of surgical treatment of 42 patients with brainstem lesions, reviews the localization of the lesion and neurological status of patients, describes available methods of intraoperative monitoring (IOM) and on-line techniques for the brainstem surgery. The materials of the paper are of practical significance for the development of brainstem surgery with IONM modifications for wider and more comfortable use by neurosurgeons.

Transcriptome-level assessment of the impact of deformed wing virus on honey bee larvae

Deformed wing virus (DWV) prevalence is high in honey bee (Apis mellifera) populations. The virus infects honey bees through vertical and horizontal transmission, leading to behavioural changes, wing deformity, and early mortality. To better understand the impacts of viral infection in the larval stage of honey bees, artificially reared honey bee larvae were infected with DWV (1.55 × 1010 copies/per larva). No significant mortality occurred in infected honey bee larvae, while the survival rates decreased significantly at the pupal stage. Examination of DWV replication revealed that viral replication began at 2 days post inoculation (d.p.i.), increased dramatically to 4 d.p.i., and then continuously increased in the pupal stage. To better understand the impact of DWV on the larval stage, DWV-infected and control groups were subjected to transcriptomic analysis at 4 d.p.i. Two hundred fifty-five differentially expressed genes (DEGs) (fold change ≥ 2 or ≤ -2) were identified. Of these DEGs, 168 genes were downregulated, and 87 genes were upregulated. Gene Ontology (GO) analysis showed that 141 DEGs (55.3%) were categorized into molecular functions, cellular components and biological processes. One hundred eleven genes (38 upregulated and 73 downregulated) were annotated by KO (KEGG Orthology) pathway mapping and involved metabolic pathways, biosynthesis of secondary metabolites and glycine, serine and threonine metabolism pathways. Validation of DEGs was performed, and the related gene expression levels showed a similar tendency to the DEG predictions at 4 d.p.i.; cell wall integrity and stress response component 1 (wsc1), cuticular protein and myo-inositol 2-dehydrogenase (iolG) were significantly upregulated, and small conductance calcium-activated potassium channel protein (SK) was significantly downregulated at 4 d.p.i. Related gene expression levels at different d.p.i. revealed that these DEGs were significantly regulated from the larval stage to the pupal stage, indicating the potential impacts of gene expression levels from the larval to the pupal stages. Taken together, DWV infection in the honey bee larval stage potentially influences the gene expression levels from larvae to pupae and reduces the survival rate of the pupal stage. This information emphasizes the consequences of DWV prevalence in honey bee larvae for apiculture.

Analyzing Roles of NUSAP1 From Clinical, Molecular Mechanism and Immune Perspectives in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common carcinomas worldwide. Our study aims to analyze how NUSAP1 affects progression of HCC from clinical, molecular mechanism and immune perspectives. Firstly, we downloaded GSE62232, GSE102079, GSE112790, and GSE121248 gene expression profile datasets from GEO database. R studio was used to screen DEGs of each dataset, and 86 overlapping DEGs of the four datasets were screened at last. Then, CytoHubba plug-in in Cytoscape software was used to screen out NUSAP1 from the 86 DEGs. Subsequently, survival analysis, clinical correlation analysis, independent prognostic analysis, and GSEA enrichment analysis of NUSAP1 were analyzed using HCC patients from GSE76427 dataset, ICGC database, and TCGA database. The results revealed that HCC patients with higher expression level of NUSAP1 had a worse prognosis. NUSAP1 was an independent prognostic factor of HCC, and it may promote HCC progress by regulating cell cycle. To further elucidate its underlying molecular mechanism, we used cBioProtal online data analysis tool to screen all co-expression genes of NUSAP1 and used top 300 co-expression genes to accomplish KEGG and GO enrichment analysis; the results confirmed that NUSAP1 accelerated progression of HCC by regulating cell cycle. We continued to draw KEGG pathway map of cell cycle using co-expression genes enriched in cell cycle pathway by KEGG online tool. The map depicted that most of co-expression genes of NUSAP1 were located in S phase and G2/M phase of the cell cycle, and they could regulate the genes in G1 phase. To further understand the mechanism of cell cycle, we also did qRT-PCR, Western blot, and flow cytometry; the results showed that NUSAP1 was closely associated with CDK4, CDK6, and cyclinD1, which could regulate G1 to S phase transition. Besides, we also analyzed correlation between NUSAP1 and immune cells using HCC patients from GSE76427 dataset, ICGC database, and TCGA database. NUSAP1 was associated with some immune cells, and we speculated that NUSAP1 could also promote HCC progression by influencing T cell CD4 memory resting and macrophage M0 through some underlying mechanism.

Task-shifting to optimize outpatient neurological care in Zambia

ObjectiveTo investigate opportunities for task shifting to decongest an outpatient neurology clinic in Zambia by describing current patient flow through the clinic and potential nodes for intervention using process mapping.BackgroundZambia has a population of approximately 18 million people with 4 full-time adult neurologists, as of 2018, who all practice at the University Teaching Hospital (UTH), the main tertiary care center in the country. As a result of this provider-to-patient ratio, the outpatient neurology clinic is overcrowded and overbooked. Task-shifting programs have shown to improve efficiency, access and quality of care through the use of less specialized healthcare workers in low- and middle-income countries (LMIC).MethodsWe evaluated patient flow in the UTH neurology outpatient clinic through the development and analysis of a process map. The characteristics of the clinic population between 2014 and 2018 were retrospectively reviewed from the clinic register. Between July and August 2018, we prospectively collected appointment lag times and time each patient spent waiting at various points in the clinic process. We conducted interviews with clinic staff and neurologists to generate a detailed process map of current pathways to care within the clinic. We then devised task-shifting strategies to help reduce patient wait times based on the overview of clinic process mapping and patient demographics.ResultsFrom 2014 to 2018, there were 4701 outpatients seen in the neurology clinic. The most common neurological diagnoses were epilepsy (39.2%), headache (21.5%) and cerebrovascular disease (16.7%). During prospective data collection, patients waited an average of 57.8 (SD 73.4) days to be seen by a neurologist. The average wait time from arrival in the clinic to departure was 4.0 (SD 2.5) h. The process map and interviews with clinic staff revealed long waiting times due to a paucity of providers. Nurses and clerks represent an influential stakeholder group, but are not actively involved in any activity to reduce wait times. A large proportion of follow-up patients were stable and seen solely to obtain medication refills.ConclusionsEpilepsy, headache, and stroke make up the largest percentage of outpatient neurological illness in Zambia. Targeting stable patients in these diagnostic categories for a task-shifting intervention may lead to substantially decreased patient wait times. Potential interventions include shifting clinical follow-ups and medication refills to less specialized healthcare workers.

WS5.6. Intraoperative Monitoring and Mapping of Visual Pathways

Background and Objective . Neurosurgical procedures along the visual pathways carry a risk of visual dysfunction. A reliable method for real time visual function monitoring assists in intraoperative decision making regarding radicality of excision and intermittent maneuvers near the optic apparatus. We present our experience of intraoperative flash visual evoked potential (VEP) monitoring. Methods 1) Anesthesia: Under total intravenous anesthesia (TIVA), the VEP shows larger amplitude and stable latency with less variability. Inhaled anesthetics, such as sevoflurane and isoflurane, markedly decrease the amplitude, and these should be avoided. 2) Stimulation: Flash VEP and ERG are recorded by flush stimulation on the closed eye lids. At least 1-minute preconditioning by flash stimulation should be done to obtain a steady VEP waveform before starting averaging. The stimulation intensity is decided by the supramaximal stimulation to the retina. As the evoked ERG is easy to record and the waveform is stable, it is utilized for checking the supramaximal value and inadequate stimulation to retina due to stimulator dislocation. 3) VEP Recording: Reference electrodes are set at A1 and A2, and these are electrically connected. Recording electrodes are set near Oz, O1, and O2. Simultaneous ERG recording is recommended as described above. Warning sign was defined as 50% decrease of baseline amplitude. 4) Optic nerve action potential: In cases of parasellar lesions such as craniopharyngiomas and giant aneyrysms, optic nerves, chiasm and tracts are sometimes streched around the lesion, and it is difficult to identify the location of the optic apparatus. In these situations, flash stimulation is deliverd as same manner as VEP, and action potentials recoeded from the operative fields facilitates to identifiy the optic apparatus. Results . VEP can be monitored in a patient with visual acuity greater than (0.03). Fifty percent decrease of VEP amplitude as warning sign detected postoperative visual aggravation in sensitivity of 99%. Reversible change in VEP means visual function to be preserved. Sudden VEP change correlates with visual acuity impairment and/or hemianopsia. The flat VEP indicates postoperative severe visual disturbance (nearly blindness). Conclusions . Intraoperative flash VEP monitoring is essential and reliable method for preserving visual function.

Map of dimorphic switching‑related signaling pathways inSporothrix schenckiibased on its transcriptome

Sporothrix schenckii (S. schenckii) induces sporotrichosis, which has gained attention in recent years due to its worldwide prevalence. The dimorphic switching process is essential for the pathogenesis of S. schenckii. Previously, overexpression of several signal transduction genes, including SsDRK1 and SsSte20, was observed during the mycelium-to-yeast transition; these were necessary for asexual development, yeast-phase cell formation, cell wall integrity and melanin synthesis. However, the mechanisms of the signaling pathways during dimorphic switching of S. schenckii remain unclear. In the present study, transcriptome sequencing of the 48-h induced yeast forms and mycelium of S. schenckii was performed. In total, 24,904,510 high-quality clean reads were obtained from mycelium samples and 22,814,406 from 48-h induced yeast form samples. Following assembly, 31,779 unigene sequences were obtained with 52.98% GC content (The proportion of guanine G and cytosine C to all bases in nucleic acid). The results demonstrated that 12,217 genes, including genes involved in signal transduction and chitin synthesis, were expressed differentially between the two stages. According to these results, a map of the signaling pathways, including two-component and heterotrimeric G-protein signaling systems, Ras and MAPK cascades associated with the dimorphic switch, was drawn. Taken together, the transcriptome data and analysis performed in the present study lay the foundation for further research into the molecular mechanisms controlling the dimorphic switch of S. schenckii and support the development of anti-S. schenckii strategies targeting genes associated with signaling pathways.

The pathways between natural disasters and violence against children: a systematic review

BackgroundNatural disasters are increasingly affecting a larger segment of the world’s population. These highly disruptive events have the potential to produce negative changes in social dynamics and the environment which increase violence against children. We do not currently have a comprehensive understanding of how natural disasters lead to violence against children despite the growing threat to human populations and the importance of violence as a public health issue. The mapping of pathways to violence is critical in designing targeted and evidence-based prevention services for children. We systematically reviewed peer-reviewed articles and grey literature to document the pathways between natural disasters and violence against children and to suggest how this information could be used in the design of future programming.MethodsWe searched 15 bibliographic databases and six grey literature repositories from the earliest date of publication to May 16, 2018. In addition, we solicited grey literature from humanitarian agencies globally that implement child-focused programming after natural disasters. Peer-reviewed articles and grey literature that presented original quantitative or qualitative evidence on how natural disasters led to violence against children were included. The authors synthesized the evidence narratively and used thematic analysis with a constant comparative method to articulate pathways to violence.ResultsWe identified 6276 unduplicated publications. Nine peer-reviewed articles and 17 grey literature publications met the inclusion criteria. The literature outlined five pathways between natural disasters and violence, including: (i) environmentally induced changes in supervision, accompaniment, and child separation; (ii) transgression of social norms in post-disaster behavior; (iii) economic stress; (iv) negative coping with stress; and (v) insecure shelter and living conditions.ConclusionsService providers would benefit from systematic documentation to a high-quality standard of all possible pathways to violence in tailoring programming after natural disasters. The identified pathways in this review provide a foundation for designing targeted prevention services. In addition, the positive coping strategies within certain affected families and communities can be leveraged in implementing strength-based approaches to violence prevention.

A high throughput toolbox for comprehensive flavor compound mapping in mint

Essential oils of the genus Mentha are extensively used as flavor ingredients in the industry. To overcome the time consuming and laborious traditional flavor analysis, a new quick, high–throughput toolbox based on a bead–beater homogenization followed by a UHPLC–MS/MS analysis has been developed and validated. While terpenes could be directly detected using atmospheric pressure chemical ionization (APCI), carbonyl compounds and alcohols required derivatization by 3–nitrophenylhydrazine (3-NPH) and glycidyltrimethylammonium chloride (GTMA) to ensure sufficient sensitivity for analysis of a single leaf. Using this approach, in total, 59 flavor-active metabolites representing the characteristic flavor of mint were quantified in leaves as well as in distilled oils using fast and robust UHPLC–MS/MS methods. The application of this toolbox enables a mapping of key pathways of mint flavor biosynthesis and can therefore support extensive breeding studies and the monitoring of chemosensate changes, depending on factors such as growth stages and environmental conditions.

Abstract 2725: Immune-cell profiling in breast cancer patients by race and triple negative breast cancer status

Abstract Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related death among American women. Underserved minorities suffer from higher mortality rates and a higher prevalence of triple-negative breast cancer (TNBC). Previous studies showed that African Americans (AA) have a higher risk for TNBC, advanced tumor, pro-inflammatory tumor microenvironment, and worse survival. Immune responses and inflammatory processes play critical roles in cancer initiation, progression, and suppression. Therefore, this study was designed to investigate the complex interplay among the tumor, microenvironment, and immune response by race and TNBC status. Tumor biopsy samples from 96 breast cancer cases were used for the NanoString PanCancer IO 360 Gene Expression Panel analysis. The panel is a 770 gene Code Set that is designed for profiling tumor biopsies and characterizing gene expression patterns associated with the tumor, the immune response, and the microenvironment that shape tumor-immune interactions. After quality control for 20 reference genes, gene expression data from 93 samples were used for subsequent data analysis with nSolver 4.0 to calculate expression changes, pathway mapping based on annotations, sample clustering (heat maps), and 14 immune cell type abundance signatures. Then we conducted a Student's t-test and ANOVA for comparison of immune cell types by patient demographics and clinical characteristics using SAS University Edition 2019. In 10 TNBC and 83 non-TNBC, the expression of 12 genes was significantly different, 4 were higher and 8 were lower in TNBC (False Discovery Rate adjusted p<0.05). AA patients had significantly higher B cells (p=0.02), T cells (p=0.03), macrophages (p=0.02), CD45 (p=0.02), and Treg cells (p=0.04) than white patients. Patients diagnosed at a young age had significantly lower neutrophil counts (p=0.02). Nonsmokers had significantly higher mast cell scores than smokers (p=0.03). Mast cells were significantly lower in ER-negative (p<0.01), PR-negative (p<0.01), and TNBC (p<0.01) patients than ER-positive, PR-positive, and non-TNBC patients. Our study results suggest that gene expression and immune cell types are different by race and TNBC status. Future data analysis will focus on 18-gene tumor inflammation signature, 15+ proprietary gene expression signatures, and 14 immune cell type abundance signatures with a single sample and dataset analysis report, and automatic predictive algorithm training. With the recent FDA accelerated approval of PD-L1 inhibitor atezolizumab as a treatment for PD-L1-positive metastatic TNBC, the NanoString PanCancer IO 360 panel may provide the capability to both discover new biomarkers and create potentially predictive signatures for immunotherapies, which in turn may help improve minority health and reduce survival disparities. Citation Format: Xiaozhuang Hu, Fernando Collado-Mesa, George R. Yang, Isildinha M. Reis, Jennifer J. Hu. Immune-cell profiling in breast cancer patients by race and triple negative breast cancer status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2725.

SARS-CoV-2 signaling pathway map: A functional landscape of molecular mechanisms in COVID-19.

Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has been declared a pandemic by WHO. The clinical manifestation and disease progression in COVID-19 patients varies from minimal symptoms to severe respiratory issues with multiple organ failure. Understanding the mechanism of SARS-CoV-2 interaction with host cells will provide key insights into the effective molecular targets for the development of novel therapeutics. Recent studies have identified virus-mediated phosphorylation or activation of some major signaling pathways, such as ERK1/2, JNK, p38, PI3K/AKT and NF-κB signaling, that potentially elicit the cytokine storm that serves as a major cause of tissue injuries. Several studies highlight the aggressive inflammatory response particularly ‘cytokine storm’ in SARS-CoV-2 patients. A depiction of host molecular dynamics triggered by SARS-CoV-2 in the form of a network of signaling molecules will be helpful for COVID-19 research. Therefore, we developed the signaling pathway map of SARS-CoV-2 infection using data mined from the recently published literature. This integrated signaling pathway map of SARS-CoV-2 consists of 326 proteins and 73 reactions. These include information pertaining to 1,629 molecular association events, 30 enzyme catalysis events, 43 activation/inhibition events, and 8,531 gene regulation events. The pathway map is publicly available through WikiPathways: https://www.wikipathways.org/index.php/Pathway:WP5115.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12079-021-00632-4.