The transplant iron score as a predictor of stem cell transplant survival

Recent studies have suggested that the presence of iron overload prior to stem cell transplantation is associated with decreased survival. Within these studies, the criteria used to define iron overload have varied considerably. Given the lack of consensus regarding the definition of iron overload in the transplant setting, we sought to methodically examine iron status among transplant patients. We studied 78 consecutive patients at risk for transfusion-related iron overload (diagnoses included AML, ALL, MDS, and aplastic anemia) who received either autologous or allogeneic stem cell transplant. Multiple measures of iron status were collected prior to transplantation and examined for their association with survival. Using this data, three potentially prognostic iron measures were identified and incorporated into a rational and unified scoring system. The resulting Transplant Iron Score assigns a point for each of the following variables: (1) greater than 25 red cell units transfused prior to transplantation; (2) serum ferritin > 1000 ng/ml; and (3) a semi-quantitative bone marrow iron stain of 6+. In our cohort, the score (range 0 to 3) was more closely associated with survival than any available single iron parameter. In multivariate analysis, we observed an independent effect of iron overload on transplant survival (p = 0.01) primarily attributable to an increase in early treatment-related deaths (p = 0.02) and lethal infections. In subgroup analysis, the predictive power of the iron score was most pronounced among allogeneic transplant patients, where a high score (≥ 2) was associated with a 50% absolute decrease in survival at one year. In summary, our results lend further credence to the notion that iron overload prior to transplant is detrimental and suggest iron overload may predispose to a higher rate of lethal infections

PDXNet portal: patient-derived Xenograft model, data, workflow and tool discovery.

We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among researchers and to make these data easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols and training materials for processing PDX data. Currently, the portal contains PDXNet model information and data resources from 334 new models across 33 cancer types. Tissue samples of these models were deposited in the NCI\u27s Patient-Derived Model Repository (PDMR) for public access. These models have 2134 associated sequencing files from 873 samples across 308 patients, which are hosted on the Cancer Genomics Cloud powered by Seven Bridges and the NCI Cancer Data Service for long-term storage and access with dbGaP permissions. The portal includes results from freely available, robust, validated and standardized analysis workflows on PDXNet sequencing files and PDMR data (3857 samples from 629 patients across 85 disease types). The PDXNet portal is continuously updated with new data and is of significant utility to the cancer research community as it provides a centralized location for PDXNet resources, which support multi-agent treatment studies, determination of sensitivity and resistance mechanisms, and preclinical trials

Novel Natural Structure Corrector of ApoE4 for Checking Alzheimer’s Disease: Benefits from High Throughput Screening and Molecular Dynamics Simulations

A major genetic suspect for Alzheimer’s disease is the pathological conformation assumed by apolipoprotein E4 (ApoE4) through intramolecular interaction. In the present study, a large library of natural compounds was screened against ApoE4 to identify novel therapeutic molecules that can prevent ApoE4 from being converted to its pathological conformation. We report two such natural compounds PHC and IAH that bound to the active site of ApoE4 during the docking process. The binding analysis suggested that they have a strong mechanistic ability to correct the pathological structural orientation of ApoE4 by preventing repulsion between Arg 61 and Arg 112, thus inhibiting the formation of a salt bridge between Arg 61 and Glu 255. However, when the molecular dynamics simulations were carried out, structural changes in the PHC-bound complex forced PHC to move out of the cavity thus destabilizing the complex. However, IAH was structurally stable inside the binding pocket throughout the simulations trajectory. Our simulations results indicate that the initial receptor-ligand interaction observed after docking could be limited due to the receptor rigid docking algorithm and that the conformations and interactions observed after simulation runs are more energetically favored and should be better representations of derivative poses in the receptor

Development of Dual Inhibitors against Alzheimer’s Disease Using Fragment-Based QSAR and Molecular Docking

Alzheimer’s (AD) is the leading cause of dementia among elderly people. Considering the complex heterogeneous etiology of AD, there is an urgent need to develop multitargeted drugs for its suppression. β-amyloid cleavage enzyme (BACE-1) and acetylcholinesterase (AChE), being important for AD progression, have been considered as promising drug targets. In this study, a robust and highly predictive group-based QSAR (GQSAR) model has been developed based on the descriptors calculated for the fragments of 20 1,4-dihydropyridine (DHP) derivatives. A large combinatorial library of DHP analogues was created, the activity of each compound was predicted, and the top compounds were analyzed using refined molecular docking. A detailed interaction analysis was carried out for the top two compounds (EDC and FDC) which showed significant binding affinity for BACE-1 and AChE. This study paves way for consideration of these lead molecules as prospective drugs for the effective dual inhibition of BACE-1 and AChE. The GQSAR model provides site-specific clues about the molecules where certain modifications can result in increased biological activity. This information could be of high value for design and development of multifunctional drugs for combating AD

Multipronged strategy for protection and motivation of healthcare workers during the COVID-19 pandemic: a real-life study

Abstract Objective: We aimed to assess risk of COVID-19 infection & seroprotection status in healthcare workers (HCWs) in both hospital and community settings following an intensive vaccination drive in India. Setting: Tertiary Care Hospital Methods: We surveyed COVID-19 exposure risk, personal protective equipment (PPE) compliance, vaccination status, mental health & COVID-19 infection rate across different HCW cadres. Elecsys® test for COVID-19 spike (Anti-SARS-CoV-2S; ACOVs) and nucleocapsid (Anti-SARS-CoV-2; ACOV) responses following vaccination and/or COVID-19 infection were measured in a stratified sample of 386 HCW. Results: We enrolled 945 HCWs (60.6% male, age 35.9 ± 9.8 years, 352 nurses, 211 doctors, 248 paramedics & 134 support staff). Hospital PPE compliance was 90.8%. Vaccination coverage was 891/945 (94.3%). ACOVs neutralizing antibody was reactive in 381/386 (98.7%). ACOVs titer (U/ml) was higher in the post-COVID-19 infection group (N =269; 242.1 ± 35.7 U/ml) than in the post-vaccine or never infected subgroup (N = 115, 204.1 ± 81.3 U/ml). RT PCR + COVID-19 infections were documented in 224/945 (23.7%) and 6 HCWs had disease of moderate severity, with no deaths. However, 232/386 (60.1%) of HCWs tested positive for nucleocapsid ACOV antibody, suggesting undocumented or subclinical COVID-19 infection. On multivariate logistic regression, only female gender [aOR 1.79, 95% CI 1.07–3.0, P = .025] and COVID-19 family contact [aOR 5.1, 95% CI 3.84–9.5, P < .001] were predictors of risk of developing COVID-19 infection, independent of association with patient-related exposure. Conclusion: Our HCWs were PPE compliant and vaccine motivated, with immunization coverage of 94.3% and seroprotection rate of 98.7%. There was no relationship between HCW COVID-19 infection to exposure characteristics in the hospital. Vaccination reduced disease severity and prevented death in HCW

Advancements in Urban Environmental Studies : Application of Geospatial Technology and Artificial Intelligence in Urban Studies

Advancements in Urban Environmental Studie

PDXNet portal: patient-derived Xenograft model, data, workflow and tool discovery

We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among researchers and to make these data easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols and training materials for processing PDX data. Currently, the portal contains PDXNet model information and data resources from 334 new models across 33 cancer types. Tissue samples of these models were deposited in the NCI's Patient-Derived Model Repository (PDMR) for public access. These models have 2134 associated sequencing files from 873 samples across 308 patients, which are hosted on the Cancer Genomics Cloud powered by Seven Bridges and the NCI Cancer Data Service for long-term storage and access with dbGaP permissions. The portal includes results from freely available, robust, validated and standardized analysis workflows on PDXNet sequencing files and PDMR data (3857 samples from 629 patients across 85 disease types). The PDXNet portal is continuously updated with new data and is of significant utility to the cancer research community as it provides a centralized location for PDXNet resources, which support multi-agent treatment studies, determination of sensitivity and resistance mechanisms, and preclinical trials