Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease

AIM: To investigate the accuracy of fungal dysbiosis in mucosa and stool for predicting the diagnosis of Crohn’s disease (CD). METHODS: Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer’s protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve (AUC) was calculated. RESULTS: All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9 (range: 6.7-17.8) years for CD children and 13.9 (3.25-18.6) years for controls, and 10/15 (67%) of the CD and 13/20 (65%) of the control subjects were boys. CD locations at diagnosis were ileal (L1) in 4 and colonic (L3) in 11 children, while CD behavior was non-stricturing and non-penetrating (B1) in 12 and stricturing (B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools (AUC = 0.85 ± 0.057) than in mucosa (AUC = 0.71 ± 0.067) (P < 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for Saccharomyces cerevisiae and S. bayanus, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa. CONCLUSION: We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD. Key Words: Fungiome, Mycobiome, Crohn’s disease, Inflammation, Saudi children Core tip: We found high accuracy of fungal dysbiosis in predicting diagnosis of Crohn’s disease (CD), a finding similar to bacterial dysbiosis. However, the higher area under the curve for the fungal dysbiosis classifier in stool (0.85 ± 0.057) than in mucosa (0.71 ± 0.067) (P < 0.001), contrasts with bacterial studies, suggesting higher accuracy of stool samples. Although the clinical application of this finding is limited at present by the high cost of fungal analysis, such information is important from a scientific viewpoint, to increase the understanding of the role of fungal flora in CD and to stimulate further studies.The authors extend their appreciations to the Deanship of Scientific Research at King Saud University in Riyadh, Kingdom of Saudi Arabia for funding this work through Research Group No [RGP-1436-007]. This work was also supported by a grant from the Simons Foundation [No. 409704] to Kirill Korolev) and by the startup fund from Boston University to Kirill Korolev. Simulations were carried out on Shared Computing Cluster at Boston University. Rajita Menon was partially supported by a Hariri Graduate Fellowship from Boston University. Harland Winter, MD received support from Martin Schlaff and the Diane and Dorothy Brooks Foundation. (RGP-1436-007 - King Saud University in Riyadh, Kingdom of Saudi Arabia; 409704 - Simons Foundation; Boston University; Hariri Graduate Fellowship from Boston University; Diane and Dorothy Brooks Foundation)Published versio

Critical Parenting’s Role in Asthma Severity: How Does A Child\u27s Emotional Adjustment Matter?

OBJECTIVE: Research shows that children with asthma are at risk for behavioral maladjustment, particularly internalizing symptoms (McQuaid et al., 2001), and that negative parenting behavior compromises child mental and physical health (Lim et al., 2011). However, pathways of effect are not clear. This study examined the relation between critical/harsh parenting and child asthma severity. A model was tested to assess whether children’s internalizing symptoms mediate the relation between maternal rejection/harshness and asthma severity. METHODS: 215 children with asthma (ages 5-12) and their families participated. Mothers reported child internalizing symptoms (CBCL) and functional asthma severity (CHAS); a Pediatric Pulmonologist reported lung function via spirometry results. Maternal criticism was observed in a 15-minute family activity; harsh/critical behavior was coded on a 1-5 scale. RESULTS: We conducted bootstrapping analyses, with 5000 samples, to examine the indirect effect of maternal rejection/criticism on pulmonary functioning via child internalizing symptoms, while controlling for child age, SES, and adherence, using the PROCESS SPSS Macro (Hayes, 2013). The estimate of the indirect effect between maternal rejection/criticism and objective lung functioning was supported, with a point estimate of -.03 (SE = .02; 95% CI = -.0846 to -.0007). However, the estimate of the indirect effect between maternal rejection/criticism and subjective/parent-reported lung functioning was not supported. CONCLUSION: Results support a theorized pathway, in which critical parenting indirectly affects a child’s lung functioning by increasing his/her internalizing symptoms (Wood et al., 2007). These findings only apply to objective physiological measures of asthma severity, perhaps suggesting a unique way that internalizing symptoms may impact lung functioning. Proposed psychological interventions include helping families understand connections between emotional and physical well-being, reducing critical parenting behavior, and treating child internalizing symptoms.https://scholarscompass.vcu.edu/gradposters/1004/thumbnail.jp

A novel molecular signature identifies mixed subtypes in renal cell carcinoma with poor prognosis and independent response to immunotherapy

BACKGROUND Renal cell carcinoma (RCC) is a heterogeneous disease comprising histologically defined subtypes. For therapy selection, precise subtype identification and individualized prognosis are mandatory, but currently limited. Our aim was to refine subtyping and outcome prediction across main subtypes, assuming that a tumor is composed of molecular features present in distinct pathological subtypes. METHODS Individual RCC samples were modeled as linear combination of the main subtypes (clear cell (ccRCC), papillary (pRCC), chromophobe (chRCC)) using computational gene expression deconvolution. The new molecular subtyping was compared with histological classification of RCC using the Cancer Genome Atlas (TCGA) cohort (n = 864; ccRCC: 512; pRCC: 287; chRCC: 65) as well as 92 independent histopathologically well-characterized RCC. Predicted continuous subtypes were correlated to cancer-specific survival (CSS) in the TCGA cohort and validated in 242 independent RCC. Association with treatment-related progression-free survival (PFS) was studied in the JAVELIN Renal 101 (n = 726) and IMmotion151 trials (n = 823). CSS and PFS were analyzed using the Kaplan-Meier and Cox regression analysis. RESULTS One hundred seventy-four signature genes enabled reference-free molecular classification of individual RCC. We unambiguously assign tumors to either ccRCC, pRCC, or chRCC and uncover molecularly heterogeneous tumors (e.g., with ccRCC and pRCC features), which are at risk of worse outcome. Assigned proportions of molecular subtype-features significantly correlated with CSS (ccRCC (P = 4.1E - 10), pRCC (P = 6.5E - 10), chRCC (P = 8.6E - 06)) in TCGA. Translation into a numerical RCC-R(isk) score enabled prognosis in TCGA (P = 9.5E - 11). Survival modeling based on the RCC-R score compared to pathological categories was significantly improved (P = 3.6E - 11). The RCC-R score was validated in univariate (P = 3.2E - 05; HR = 3.02, 95% CI: 1.8-5.08) and multivariate analyses including clinicopathological factors (P = 0.018; HR = 2.14, 95% CI: 1.14-4.04). Heterogeneous PD-L1-positive RCC determined by molecular subtyping showed increased PFS with checkpoint inhibition versus sunitinib in the JAVELIN Renal 101 (P = 3.3E - 04; HR = 0.52, 95% CI: 0.36 - 0.75) and IMmotion151 trials (P = 0.047; HR = 0.69, 95% CI: 0.48 - 1). The prediction of PFS significantly benefits from classification into heterogeneous and unambiguous subtypes in both cohorts (P = 0.013 and P = 0.032). CONCLUSION Switching from categorical to continuous subtype classification across most frequent RCC subtypes enables outcome prediction and fosters personalized treatment strategies

Pink Ocean Strategy: Democratizing Business Knowledge for Social Growth and Innovation

In a constantly and rapidly changing world, innovation and organizational sustainability keep on being redefined. The integration of Blue and Green Ocean strategies can deliver social innovation and impact directly the lives of millions of people globally while assuring the needed organizational sustainability and profitability. This approach introduces the Pink Ocean Strategy concept, which cares about human life, integrity and dignity to booster innovation efforts. The new Pink Ocean Strategy is executed through the Company Democracy Model, the model for people, to embrace anyone who has and can share data, information, knowledge as well as wisdom creation for the good of the society, community and the humanity. The paper presents the six stages of the Company Democracy Model adjusted to navigate organizations into Pink Oceans, the overall strategic management framework, the pre and post conditions of each stage and the expected results per stage, enables this navigation to Pink Oceans

Dynamical behavior of a cancer growth model with chemotherapy and boosting of the immune system

In this study, we set up and analyze a cancer growth model that integrates a chemotherapy drug with the impact of vitamins in boosting and strengthening the immune system. The aim of this study is to determine the minimal amount of treatment required to eliminate cancer, which will help to reduce harm to patients. It is assumed that vitamins come from organic foods and beverages. The chemotherapy drug is added to delay and eliminate tumor cell growth and division. To that end, we suggest the tumor-immune model, composed of the interaction of tumor and immune cells, which is composed of two ordinary differential equations. The model’s fundamental mathematical properties, such as positivity, boundedness, and equilibrium existence, are examined. The equilibrium points’ asymptotic stability is analyzed using linear stability. Then, global stability and persistence are investigated using the Lyapunov strategy. The occurrence of bifurcations of the model, such as of trans-critical or Hopf type, is also explored. Numerical simulations are used to verify the theoretical analysis. The Runge–Kutta method of fourth order is used in the simulation of the model. The analytical study and simulation findings show that the immune system is boosted by regular vitamin consumption, inhibiting the growth of tumor cells. Further, the chemotherapy drug contributes to the control of tumor cell progression. Vitamin intake and chemotherapy are treated both individually and in combination, and in all situations, the minimal level required to eliminate the cancer is determined

The role of religion in al-Qaeda’s violence

This chapter explores the role of religion in jihadist violence by applying recent insights from the field of religious studies to the case of al-Qaeda. Whereas religion is often perceived as an explanatory factor in al-Qaeda’s attacks, the chapter demonstrates that the meanings attributed to religion are dependent on particular historical and cultural contexts. As a result, the chapter argues, the concept of religion cannot be consistently separated from its alleged secular counterpart, which makes any distinction between religious violence and secular violence arbitrary. Moreover, in the case of al-Qaeda’s violence, alleged religious and secular factors appear to be strongly intertwined and cannot be separated consistently. Thus, the chapter argues, whereas particular beliefs, values and practices deemed ‘religious’ by the perpetrators may fuel jihadist violence in particular contexts, questions of whether religion, as an abstract category, causes or contributes to violence are inconsistent. Instead, it is more fruitful to explore why questions on the role of religion in al-Qaeda’s violence have been so prevalent over the last years. The chapter concludes that, for al-Qaeda, presenting the perceived conflict between Islam and the West as a religious conflict reconfirms and authorises the group’s self-definition and facilitates and legitimises its violence

Effect of egg turning and incubation time on carbonic anhydrase gene expression in the blastoderm of the Japanese quail (Coturnix c. japonica)

(1) The gene expression of carbonic anhydrase, a key enzyme for the production sub-embryonic fluid (SEF), was assessed in turned and unturned eggs of the Japanese quail. The plasma membrane-associated isoforms CA IV, CAIX, CA XII, CA XIV, and the cytoplasmic isoform CA II, were investigated in the extra-embryonic tissue of the blastoderm and in embryonic blood. (2) Eggs were incubated at 37.6C, c. 60% R.H., and turned hourly (90 ) or left unturned. From 48 to 96 hours of incubation mRNA was extracted from blastoderm tissue, reverse-transcribed to cDNA and quantified by real-time qPCR using gene-specific primers. Blood collected at 96h was processed identically. (3) Blastoderm CAIV gene expression increased with the period of incubation only in turned eggs, with maxima at 84 and 96h of incubation. Only very low levels were found in blood. (4) Blastoderm CA II gene expression was greatest at 48 and 54h of incubation, subsequently declining to much lower levels and una ected by turning. Blood CA II gene expression was about 25-fold greater than that in the blastoderm. (5) The expression of CA IX in the blastoderm was the highest of all isoforms, yet unaffected by turning. CA XII did not amplify and CA XIV was present at unquantifiable low levels. (6) It is concluded that solely gene expression for CA IV is sensitive to egg turning, and that increased CA IV gene expression could account for the additional SEF mass found at 84-96h of incubation. in embryos of turned eggs

Neighborhood Characteristics and Colorectal Cancer Survivors\u27 Quality of Care

Purpose: Quality cancer care entails receipt of a Survivorship Care Plan (SCP). The purpose of this study was to determine differences in SCP delivery by patient-level and neighborhood characteristics. Methods: We obtained California cancer registry data on individuals who were diagnosed with stage I, II, or III colorectal cancer (CRC) between 2012 and 2015 and resided in predetermined geographic areas. We then mailed them a questionnaire, which queried about receipt of a SCP and its content. SCP was defined by content, as summary of cancer treatment, cancer surveillance recommendations, and/or an individualized preventive care. Using logistic regression modeling, each measure of SCP, as well as the summary measure (none vs. any), was evaluated by person-level characteristics. Subsequently, neighborhood-level characteristics were added to the model to explore their additional value. Results: Overall 80% of CRC survivors received a SCP. Receipt of SCPs was associated with person-level characteristics, while neighborhood characteristics did not make an additional contribution. Young, male employed survivors and those with more recent diagnoses or later cancer stages had greater odds of receiving a SCP. Conclusion: When providing SCPs, health care providers prioritize patient groups who they may perceive as vulnerable or likely to benefit from SCPs