Malassezia-associated skin diseases in the pediatric population.

Malassezia are yeast species that commonly colonize healthy skin. However, they have been associated with or implicated in the pathogenesis of numerous skin disorders, particularly in the setting of pediatric populations. In this review, we will focus on several Malassezia-associated skin conditions manifesting in infants, children, and adolescents: pityriasis versicolor, Malassezia folliculitis, infantile and adolescent seborrheic dermatitis, head and neck dermatitis, and neonatal cephalic pustulosis. We examine the literature and provide an overview of these conditions, including clinical presentation in diverse skin colors, diagnosis, risk factors, and treatment and management. Additionally, we summarize and highlight some of the proposed theories on the role of Malassezia spp. in the pathogenesis of these skin conditions.

Population-Based Serologic Survey of Vibrio cholerae Antibody Titers before Cholera Outbreak, Haiti, 2022.

A Vibrio cholerae O1 outbreak emerged in Haiti in October 2022 after years of cholera absence. In samples from a 2021 serosurvey, we found lower circulating antibodies against V. cholerae lipopolysaccharide in children <5 years of age and no vibriocidal antibodies, suggesting high susceptibility to cholera, especially among young children.

Structure-based pharmacophore modeling and DFT studies of Indian Ocean-derived red algal compounds as PI3Kα inhibitors.

Phosphoinositide kinases (PIKs) are a type of lipid kinase that acts as an upstream activator of oncogenic signaling. Presently accessible therapeutic compounds have downsides, such as toxicity and dubious efficacy, as well as lengthy treatment durations, which have bred resistance. Here we attempt to screen the Indian Ocean-derived red algal compounds to be used as a promising lead for PI3Kα inhibitor development. Experimental structure of the PI3K alpha Isoform-Specific Inhibitor alpelisib complex-based pharmacophore model was constructed and used as key to mark off the suitable lead compounds from the pool of marine-derived red algal compounds of Indian Ocean. Besides, the study encompasses pharmacophore scaffold screening as well as physicochemical and pharmacokinetic parameter assessment. We employed molecular docking and molecular dynamics simulation to assess the binding type and stability of 21 red algal derivatives. Twelve compounds demonstrated a sustained binding mode within the PI3Kα binding pocket with an optimal protein backbone root-mean-square deviation, also prompted hydrogen bonding throughout the simulations, and also implies that these MNPs have firmly mediated the interaction with prime hinge region residues in the PI3Kα ATP binding pocket. DFT studies revealed that proposed compounds had the greatest occupied molecular orbital electrophilicity index, basicity, and dipole moment, all of which attributed their stability as well as binding affinity at the PI3Kα active site. Our study's findings revealed that CMNPD31054, CMNPD4798, CMNPD27861, CMNPD4799, CMNPD27860, CMNPD9533, CMNPD3732, CMNPD4221, CMNPD31058, CMNPD31052, CMNPD29281, and CMNPD31055 can be used as lead compounds for PI3KΑ isoform inhibitors design.

Mapping 2 Decades of Research in Health Services Research, Health Policy, and Health Economics Journals.

OBJECTIVE: To identify major research topics and exhibit trends in these topics in 15 health services research, health policy, and health economics journals over 2 decades. DATA SOURCES: The study sample of 35,159 abstracts (1999-2020) were collected from PubMed for 15 journals. STUDY DESIGN: The study used a 3-phase approach for text analyses: (1) developing the corpus of 40,618 references from PubMed (excluding 5459 of those without abstract or author information); (2) preprocessing and generating the term list using natural language processing to eliminate irrelevant textual data and identify important terms and phrases; (3) analyzing the preprocessed text data using latent semantic analysis, topic analyses, and multiple correspondence analysis. PRINCIPAL FINDINGS: Application of analyses generated 16 major research topics: (1) implementation/intervention science; (2) HIV and women's health; (3) outcomes research and quality; (4) veterans/military studies; (5) provider/primary-care interventions; (6) geriatrics and formal/informal care; (7) policies and health outcomes; (8) medication treatment/therapy; (9) patient interventions; (10) health insurance legislation and policies; (11) public health policies; (12) literature reviews; (13) cost-effectiveness and economic evaluation; (14) cancer care; (15) workforce issues; and (16) socioeconomic status and disparities. The 2-dimensional map revealed that some journals have stronger associations with specific topics. Findings were not consistent with previous studies based on user perceptions. CONCLUSION: Findings of this study can be used by the stakeholders of health services research, policy, and economics to develop future research agendas, target journal submissions, and generate interdisciplinary solutions by examining overlapping journals for particular topics.

Considerations in Methods and Timing for Delivery of Genetic Counseling Information to Pediatric Oncology Patients and Families.

Many pediatric oncology patients and their families may benefit from genetic counseling and testing; however, identifying the best timing and delivery method for these referrals is sometimes a challenge. The goal of this study was to understand how and when caregivers prefer to receive information about genetic counseling and testing. A total of 56 surveys completed by caregivers at The Johns Hopkins Hospital Pediatric Oncology unit in Baltimore, Maryland were analyzed. A sizeable subset of respondents was interested in receiving information about the availability of genetic counseling from an oncology doctor or nurse, but not a genetic counselor (n=13/55, 24%). Most respondents preferred to be informed about genetic services at diagnosis (n=28/54, 52%) or within 1 to 2 months of diagnosis (n=14/54, 26%). In conclusion, patients and their families may benefit from prompt and early recognition of the risk of cancer predisposition syndromes, preferably within the first 2 months following diagnosis. Oncology professionals are an important source of information, and can introduce the availability of genetic counseling services and motivate families to undergo genetic testing, though alternative communication methods such as brochures may also be useful.

Renal claudin-14 expression is not required for regulating Mg2+ balance in mice.

The kidneys play a crucial role in maintaining Ca2+ and Mg2+ homeostasis by regulating these minerals' reabsorption. In the thick ascending limb of Henle's loop (TAL), Ca2+ and Mg2+ are reabsorbed through the tight junctions by a shared paracellular pathway formed by claudin-16 and claudin-19. Hypercalcemia activates the Ca2+-sensing receptor (CaSR) in the TAL, causing upregulation of pore-blocking claudin-14 (CLDN14), which reduces Ca2+ and Mg2+ reabsorption from this segment. In addition, a high-Mg2+ diet is known to increase both urinary Mg2+ and Ca2+ excretion. Since Mg2+ may also activate CaSR, we aimed to investigate whether CaSR-dependent increases in CLDN14 expression also regulate urinary Mg2+ excretion in response to hypermagnesemia. Here, we show that a Mg2+-enriched diet increased urinary Mg2+ and Ca2+ excretion in mice; however, this occurred without detectable changes in renal CLDN14 expression. The administration of a high-Mg2+ diet to Cldn14-/- mice did not cause more pronounced hypermagnesemia or significantly alter urinary Mg2+ excretion. Finally, in vitro evaluation of CaSR-driven Cldn14 promoter activity in response to increasing Mg2+ concentrations revealed that Cldn14 expression only increases at supraphysiological extracellular Mg2+ levels. Together, these results suggest that CLDN14 is not involved in regulating extracellular Mg2+ balance following high dietary Mg2+ intake.NEW & NOTEWORTHY Using transgenic models and in vitro assays, this study examined the effect of Mg2+ on regulating urinary excretion of Ca2+ and Mg2+ via activation of the Ca2+-sensing receptor-claudin 14 (CLDN14) pathway. The study suggests that CLDN14 is unlikely to play a significant role in the compensatory response to hypermagnesemia.

Improving Detection of Cancer Predisposition Syndromes in Pediatric Oncology.

Implementation and adherence to consensus statement criteria for referral of pediatric cancer patients for genetic evaluation are critical to identify the 5% to 10% with a genetic cancer predisposition syndrome. The authors implemented a Plan-Do-Study-Act quality improvement initiative aimed at increasing referrals of at-risk patients. Retrospective chart review was followed by educational intervention-with impact assessed over a 9-month prospective chart review. Referral rate improved >2-fold and there was an improvement in documented oncologic history to at least a third-degree relative. The integration of quality improvement can be an effective tool to improve the referral of patients with an elevated risk for a cancer predisposition syndrome.

Hospital staffing patterns and safety culture perceptions: The mediating role of perceived teamwork and perceived handoffs.

BACKGROUND: As hospitals are under increasing pressure to improve quality and safety, safety culture has become a focal issue for high-risk organizations, including hospitals. Prior research has examined how structural characteristics directly impact safety culture. However, and based on Donabedian's structure-process-outcome quality model, there is a need to understand the processes that intermediate the relationship between structural characteristics and safety culture perceptions. PURPOSE: The processes by which registered nurse (RN) and hospitalist staffing may affect safety culture perceptions were examined in this study. Specifically, this study investigates the processes of perceived teamwork across units and perceived handoffs. METHODOLOGY: Data sources for this research included Hospital Survey on Patient Safety Culture from the Agency for Healthcare Research and Quality, the American Hospital Association's Annual Survey Data, the American Hospital Association Information Technology supplement, and the Area Health Resource File. Two separate mediation models for each process were used. Propensity weights were assigned to each hospital in the sample ( N = 207) to adjust for potential nonresponse bias of hospitals that did not assess employee's safety culture perceptions. RESULTS: Results suggest that RN staffing influences safety culture perceptions, but hospitalist staffing does not. In addition, RN staffing has an indirect effect on safety culture perceptions through better processes. PRACTICE IMPLICATIONS: Our study sheds light on how staffing affects safety culture perceptions. Specifically, our findings suggest that positive perceptions of teamwork across units and handoffs are integral in the relationship between RN staffing and safety culture perceptions. Hospital managers should, therefore, invest resources in staff recruitment and retention. In addition, a targeted focus on perceived teamwork and handoffs may allow hospital managers to improve safety culture perceptions.

Resource-based view on safety culture's influence on hospital performance: The moderating role of electronic health record implementation.

BACKGROUND: Patient safety and safety culture have received increasing attention from agencies such as the Agency of Healthcare Research and Quality and the Institute of Medicine. Safety culture refers to the fundamental values, attitudes, and perceptions that provide a unique source of competitive advantage to improve performance. This study contributes to the literature and expands understanding of safety culture and hospital performance outcomes when considering electronic health record (EHR) usage. PURPOSE: Based on the resource-based view of the firm, this study examined the association between safety culture and hospital quality and financial performance in the presence of EHR. METHODOLOGY/APPROACH: Data consist of the 2016 Hospital Survey on Patient Safety, Hospital Compare, American Hospital Association's annual survey, and the American Hospital Association's Information Technology supplement. Our final analytic sample consisted of 154 hospitals. We used a two-part nested regression model approach. RESULTS/CONCLUSION: Safety culture has a direct positive relationship with financial performance (operating margin). Furthermore, having basic EHR as compared to not having EHR further enhances this positive relationship. On the other hand, safety culture does not have a direct association with quality performance (readmissions) in most cases. However, safety culture coupled with basic EHR functionalities, compared to not having EHR, is associated with lower readmissions. PRACTICE IMPLICATIONS: Hospitals should strive to improve patient safety culture as part of their strategic plan for quality improvement. In addition, hospital managers should consider implementing EHR as a resource that can support safety culture's effect on outcomes such as financial and quality performance indicators. Future studies can examine the differences between basic and advanced EHR presence in relation to safety culture.

Factors affecting quality of life in children and adolescents with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders.

Hypermobile Ehlers-Danlos syndrome (hEDS) is a hereditary disorder of connective tissue, often presenting with complex symptoms can include chronic pain, fatigue, and dysautonomia. Factors influencing functional disability in the pediatric hEDS population are incompletely studied. This study's aims were to assess factors that affect quality of life in children and adolescents with hEDS. Individuals with hEDS between the ages 12-20 years and matched parents were recruited through retrospective chart review at two genetics clinics. Participants completed a questionnaire that included the Pediatric Quality of Life Inventory (PedsQL™), PedsQL Multidimentional Fatigue Scale, Functional Disability Inventory, Pain-Frequency-Severity-Duration Scale, the Brief Illness Perception Questionnaire, measures of anxiety and depression, and helpful interventions. Survey responses were completed for 47 children and adolescents with hEDS/hypermobility spectrum disorder (81% female, mean age 16 years), some by the affected individual, some by their parent, and some by both. Clinical data derived from chart review were compared statistically to survey responses. All outcomes correlated moderately to strongly with each other. Using multiple regression, general fatigue and pain scores were the best predictors of the PedsQL total score. Additionally, presence of any psychiatric diagnosis was correlated with a lower PedsQL score. Current management guidelines recommend early intervention to prevent disability from deconditioning; these results may help identify target interventions in this vulnerable population.

Pain and sleep quality in children with non-vascular Ehlers-Danlos syndromes.

The objective of this study was to explore the factors contributing to quality of life in pediatric patients with non-vascular Ehlers-Danlos syndromes (EDS). Data were analyzed on 41 children with a diagnosis of non-vascular EDS from the de-identified data available from the National Institute on Aging (NIA) study of heritable disorders of connective tissue. Children under age 19 years were seen as part of a long-term evaluation project from 2003 to 2013 on a larger natural history of patients with heritable disorders of connective tissue. Data collected included medical history, physical examination findings, diagnostic study results, and responses on validated questionnaires. We reviewed a sub-cohort of children with a diagnosis of non-vascular EDS and explored pain severity and interference via the Brief Pain Inventory, and sleep quality via the Pittsburgh Sleep Quality Index. Pain severity had a strong correlation with pain interference, and both were similar to other disorders that include chronic pain reported in the literature. Sleep quality did not correlate with pain severity or interference, but all patients had poor sleep quality in comparison to historical controls. We conclude that pain and sleep are significant issues in the pediatric non-vascular EDS population, and future research may be directed toward these issues.

More yeast, more problems?: reevaluating the role of Malassezia in seborrheic dermatitis.

Seborrheic dermatitis (SD) is an inflammatory skin disorder and eczema subtype increasingly recognized to be associated with significant physical, psychosocial, and financial burden. The full spectrum of SD, including dandruff localized to the scalp, is estimated to affect half of the world's population. Despite such high prevalence, the exact etiopathogenesis of SD remains unclear. Historically, many researchers have theorized a central, causative role of Malassezia spp. based on prior studies including the proliferation of Malassezia yeast on lesional skin of some SD patients and empiric clinical response to antifungal therapy. However, upon closer examination, many of these findings have not been reproducible nor consistent. Emerging data from novel, targeted anti-inflammatory therapeutics, as well as evidence from genome-wide association studies and murine models, should prompt a reevaluation of the popular yeast-centered hypothesis. Here, through focused review of the literature, including laboratory studies, clinical trials, and expert consensus, we examine and synthesize the data arguing for and against a primary role for Malassezia in SD. We propose an expansion of SD pathogenesis and suggest reframing our view of SD to be based primarily on dysregulation of the host immune system and skin epidermal barrier, like other eczemas.

The Global Prevalence of Seborrheic Dermatitis: A Systematic Review and Meta-Analysis.

Importance: Seborrheic dermatitis is a prevalent chronic inflammatory skin disease, yet its global prevalence, pathogenesis, and epidemiology remain inadequately defined. Objective: To provide a detailed estimation of the global prevalence of seborrheic dermatitis, analyze demographic variations, and explore differences in various settings. Data Sources: Embase, PubMed, Scopus, and Cochrane Database of Systematic Reviews were searched from inception through October 2023. Study Selection: Original investigations on seborrheic dermatitis prevalence were included after duplicate screening of titles, abstracts, and full articles, including only studies with clinician-diagnosed cases. Data Extraction and Synthesis: Following PRISMA guidelines, data were extracted and quality was assessed independently by multiple reviewers. A random-effects model using restricted maximum likelihood was used for meta-analysis and subgroup analyses. Main Outcome and Measure: The primary outcome was the pooled estimate of global seborrheic dermatitis prevalence. Results: From 1574 identified articles, 121 studies were included, encompassing 1 260 163 individuals and revealing a pooled global seborrheic dermatitis prevalence of 4.38% (95% CI, 3.58%-5.17%), with significant heterogeneity (I2 = 99.94%). Subgroup analyses showed variations by age, with a higher prevalence in adults (5.64% [95% CI, 4.01%-7.27%]) compared to children (3.70% [95% CI, 2.69%-4.80%]) and neonates (0.23% [95% CI, 0.04%-0.43%]). Geographic analyses indicated variability, with the highest prevalence in South Africa (8.82% [95% CI, 3.00%-14.64%]) and the lowest in India (2.62% [95% CI, 1.33%-3.92%]). Conclusions and Relevance: This comprehensive meta-analysis provides a detailed estimation of the global prevalence of seborrheic dermatitis, highlighting significant variability across different demographics and settings.

Childhood trauma, resilience, psychopathology and social functioning in schizophrenia: A network analysis.

The affective pathway to psychosis implicates affective symptoms and neuroticism as mediating steps between childhood trauma and symptoms of schizophrenia. Prior research seldom examined the interplay between childhood trauma, resilience, personality, social functioning and symptoms in schizophrenia patients. This study recruited 290 schizophrenia patients, and constructed a regularized partial correlation network of childhood trauma, resilience, big-five personality traits, symptoms and social functioning. We further applied flow diagram and shortest path analysis to clarify how different childhood trauma types would contribute to and reach different symptoms. In the network, emotional and physical abuse showed the highest expected influence, and resilience showed the highest strength. In flow diagrams, all nodes together contributed two-thirds of variance of social functioning (which had highest predictability). Among childhood trauma types, emotional abuse contributed most to positive symptoms; physical neglect contributed most to negative, depressive and disorganized symptoms. Childhood abuse reached positive symptoms via neuroticism and depressive symptoms, yet it reached negative symptoms via physical neglect and social functioning. Childhood neglect reached positive symptoms via resilience, conscientiousness, neuroticism and depressive symptoms, yet it reached negative symptoms via social functioning. Our findings support that different childhood trauma types contribute to different symptoms, and interacts with resilience, personality and social functioning.

Negative symptoms in treatment-resistant schizophrenia and its relationship with functioning.

BACKGROUND: Recent operational criteria for treatment-resistant schizophrenia (TRS) recognized positive and negative symptoms. TRS patients may have heterogeneity in negative symptoms, but empirical data were lacking. We aimed to characterize TRS patients based on negative symptoms using cluster analysis, and to examine between-cluster differences in social functioning. METHODS: We administered the Clinical Assessment Interview of Negative symptoms (CAINS), Brief Negative Symptom Scale (BNSS), the Positive and Negative Syndrome Scale (PANSS) and the Social and Occupational Functional Assessment (SOFAS to 126 TRS outpatients. All patients also completed the Temporal Experience of Pleasure Scale (TEPS), the Emotion Expressivity Scale (EES), and the Social Functional Scale (SFS). A two-stage hierarchical cluster analysis was performed with the CAINS, TEPS and EES as clustering variables. We validated the clusters using ANOVAs to compare group differences in the BNSS, PANSS, SOFAS and SFS. RESULTS: Clustering indices supported a 3-cluster solution. Clusters 1 (n = 46) and 3 (n = 16) exhibited higher CAINS scores than Cluster 2 (n = 64), and were negative-symptom TRS subtypes. Cluster 1 reported lower TEPS than Cluster 3; but Cluster 3 reported lower EES than Cluster 1. Upon validation, Clusters 1 and 3 exhibited higher BNSS scores than Cluster 2, but only Cluster 1 exhibited lower SOFAS and higher PANSS general symptoms than Cluster 2. Both Clusters 1 and 3 had higher self-report functioning than Cluster 2. CONCLUSION: We provided evidence for heterogeneity of negative symptoms in TRS. Negative symptoms can characterize TRS patients and predict functional outcome.

In silico and in vitro studies on inhibitors for SARS-CoV-2 non-structural proteins with dual herbal combination of Withania somnifera with five rasayana herbs.

Being highly transmissible, severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected millions of people causing devastating global impact and has also not slowed down even after vaccination. The emerges of new strains has made more concerns than the original one. We need a new therapeutic approach against the disease. Our comprehensive in silico study investigates dual herbal combinatorial methanolic extracts of W. somnifera (W) alone and with P. emblica (P) (W:P/1:4) , T. sinensis (T) (W:T/1:4), B. monnieri (B) (W:B/1:1), O. basilicum (O) (W:O/1:4), A. racemosus (A) (W:A/4:1) for potential four phytochemicals as ligands docked with eight COVID-19 Nonstructural proteins (nsp)-main protease (PDB ID:6LU7), papain-like protease (6WUU), helicase ADP (2XZL), N7-methyltransferase (5C8S), endoribonuclease (6WLC), 2'O-methyltransferase (6WVN), RNA dependent RNA polymerase (6M71), and 3Cprotease (6YNQ) along with Remdesivir and Hydroxychloroquine. Ligands from W:P/1:4 showed remarkable docking score (-9.01 kcal/mol) 6M71-(8E,11E,14E)-eicosa-8,11,14-trienoicacidmethylester (EIS) and (-9.99 kcal/mol) 6YNQ-N-[(E)-[4-[(2-methoxydibenzofuran-3-yl)amino]-4-oxobutan-2-ylidene]amino] 4nitrobenzamide (MET). Further, MD simulations were studied for 100 ns and showed the complexes were flexible, stable in the binding pockets of the receptors, and MM-PBSA analysis determined high binding energy of -129.673 ± 15.284 and -134.594 ± 7.085 for 6M71-EIS (Asn496, Lys577, Arg569) and 6YNQ-MET (Cys145, His41). Finally, in vitro JURKAT E6.1 cell lines treated with W:P/1:4 and W:O/1:4 methanolic extracts yielded 44.06 and 31.53 ng/mL levels for interferon alpha to counteract an external stimulus by establishing an antiviral state. Thus, nsp is targeted to design effective antiviral drugs for developing an effective therapeutic approach to combat viral RNA synthesis, processing, and suppression of host immunity.Communicated by Ramaswamy H. Sarma.

Epidemiology and clinical manifestations of reported Lyme disease cases: Data from the Canadian Lyme disease enhanced surveillance system.

Lyme disease cases reported in seven Canadian provinces from 2009 to 2019 through the Lyme Disease Enhanced Surveillance System are described herein by demographic, geography, time and season. The proportion of males was greater than females. Bimodal peaks in incidence were observed in children and older adults (≥60 years of age) for all clinical signs except cardiac manifestations, which were more evenly distributed across age groups. Proportions of disease stages varied between provinces: Atlantic provinces reported mainly early Lyme disease, while Ontario reported equal proportions of early and late-stage Lyme disease. Early Lyme disease cases were mainly reported between May through November, whereas late Lyme disease were reported in December through April. Increased awareness over time may have contributed to a decrease in the proportion of cases reporting late disseminated Lyme disease. These analyses help better describe clinical features of reported Lyme disease cases in Canada.

A population-based serological survey of Vibrio cholerae antibody titers in Ouest Department, Haiti in the year prior to the 2022 cholera outbreak.

After three years with no confirmed cholera cases in Haiti, an outbreak of Vibrio cholerae O1 emerged in October 2022. Levels of pre-existing antibodies provide an estimate of prior immunologic exposure, reveal potentially relevant immune responses, and set a baseline for future serosurveillance. We analyzed dried blood spots collected in 2021 from a population-weighted representative cross-sectional serosurvey in two communes in the Ouest Department of Haiti. We found lower levels of circulating IgG and IgA antibodies against V. cholerae lipopolysaccharide (LPS, IgG and IgA p<0.0001) in those below 5 years of age compared to those five years and older. Among a subset of patients with higher titers of antibodies, we were unable to detect any functional (vibriocidal) antibodies. In conclusion, the lack of detectable functional antibodies, and age-discordant levels of V. cholerae LPS IgG, suggest that populations in Haiti may be highly susceptible to cholera disease, especially among young children.

Comprehensive Study of Human FBXW7 Deleterious nsSNP's Functional Inference and Susceptibility to Gynaecological Cancer.

Cancer is one of the world's major causes of mortality, and it plays a most important role in the world's declining life expectancy. F-box and WD-40 domain protein 7 (FBXW7), a typical participant of the F-box family of proteins, has been considered as an anti-tumor protein and one of the maximum deregulated ubiquitin-proteasome system proteins in uterine carcinosarcoma, endometrial clear cell carcinoma and cervical carcinoma with the greatest prevalence of alterations. FBXW7 variants with known clinical significance, as well as non-synonymous single nucleotide polymorphisms (nsSNPs) in the F-Box and WD40 domains, were evaluated using functionality prediction web resources. Upon analysing the seventy-three deleterious nsSNP's impact on protein stability and function, we identified that forty-one nsSNPs of WD40 domain and three of F-Box domain imply decreased stability of the FBXW7 structure. Next to TP53 and PTEN, FBXW7 was reported with the highest percentage of arginine substitution among mutations related to cancer. The current research concentrated on two arginine residue locations (Arg465, Arg505) within the WD40-repeat domain, which is vital for substrate binding. Computational analysis revealed significant deviation in stability and structural configuration of mutants R505L, R465H, R465P, R505G, R505C, R465C, R505S and R505L structures. Protein-protein interaction network of FBXW7 populated with promising hub proteins NOTCH1, c-Myc, CCNE1, STYX, KLG5, SREB1, NFKB2, SKP1 and CUL1; thus, alteration in the FBXW7 leads to aberration in their signalling pathways as well as their substrate binding ability makes this protein as attractive target for personalized therapeutic intervention.