Magnetic resonance spectroscopy — Revisiting the biochemical and molecular milieu of brain tumors

AbstractBackgroundMagnetic resonance spectroscopy (MRS) is an established tool for in-vivo evaluation of the biochemical basis of human diseases. On one hand, such lucid depiction of ‘live biochemistry’ helps one to decipher the true nature of the pathology while on the other hand one can track the response to therapy at sub-cellular level. Brain tumors have been an area of continuous interrogation and instigation for mankind. Evaluation of these lesions by MRS plays a crucial role in the two aspects of disease management described above.Scope of reviewPresented is an overview of the window provided by MRS into the biochemical aspects of brain tumors. We systematically visit each metabolite deciphered by MRS and discuss the role of deconvoluting the biochemical aspects of pathologies (here in context of brain tumors) in the disease management cycle. We further try to unify a radiologist's perspective of disease with that of a biochemist to prove the point that preclinical work is the mother of the treatment we provide at bedside as clinicians. Furthermore, an integrated approach by various scientific experts help resolve a query encountered in everyday practice.Major conclusionsMR spectroscopy is an integral tool for evaluation and systematic follow-up of brain tumors. A deeper understanding of this technology by a biochemist would help in a swift and more logical development of the technique while a close collaboration with radiologist would enable definitive application of the same.General significanceThe review aims at inciting closer ties between the two specialists enabling a deeper understanding of this valuable technology

Loss and Damage from Climate Change: Building Knowledge and Capacity in the Most Vulnerable Countries

Mitigation and adaptation are at the center of global climate negotiations. However, as climate change impacts become more frequent and more severe, these two well-accepted pillars of climate policy are not sufficient. Burgeoning damage and loss from climate change is inevitable, and it has become urgent to expedite international policy work on Loss and Damage (L&D) response. L&D has been identified as a policy action area within the United Nations Framework Convention on Climate Change (UNFCCC) system; however, progress has been extremely slow. By undertaking a review of the current situation, including country-level examples from Bangladesh, Nepal, and Vanuatu, we consider the immediate needs of the most vulnerable countries and suggest high-priority actions to move forward. These actions include: 1. Clarifying conceptual dilemmas around loss and damage vis-à-vis adaptation, mitigation, and disaster risk reduction, demonstrating how L&D policy concepts can be implemented. 2. Assisting developing and vulnerable countries in undertaking diagnostic assessments with respect to loss and damage and identifying policy and institutional options to advance L&D at national and sub-national levels. 3. Facilitating knowledge-sharing among developing and most vulnerable countries with regard to policy, risk governance, response to Loss and Damage, and ensuring socially inclusive responses. 4. Helping create learning opportunities for key policy and research champions in vulnerable countries. 5. Helping develop a dedicated L&D financing system at national and sub-national levels. 6. Providing technical assistance to Least Developed Countries (LDCs) and the Alliance of Small Island States (AOSIS) to formulate a coherent approach to L&D negotiation within the UNFCCC system as well as enhanced representation of Loss and Damage situations for the Global Stocktake 2023 international conventions. 7. Building the Research and Development (R&D) capacity of national research and training groups in most vulnerable countries vis-à-vis comprehensive risk management, including how national institutions can deliver with respect to multiple outcomes including the Sustainable Development Goals (SDGs), Disaster Risk Reduction (DRR), adaptation at large and L&D. 8. Developing and strengthening national database systems to facilitate loss and damage accounting and financial delivery

Distributed learning on 20 000+ lung cancer patients - The Personal Health Train

Background and purpose Access to healthcare data is indispensable for scientific progress and innovation. Sharing healthcare data is time-consuming and notoriously difficult due to privacy and regulatory concerns. The Personal Health Train (PHT) provides a privacy-by-design infrastructure connecting FAIR (Findable, Accessible, Interoperable, Reusable) data sources and allows distributed data analysis and machine learning. Patient data never leaves a healthcare institute. Materials and methods Lung cancer patient-specific databases (tumor staging and post-treatment survival information) of oncology departments were translated according to a FAIR data model and stored locally in a graph database. Software was installed locally to enable deployment of distributed machine learning algorithms via a central server. Algorithms (MATLAB, code and documentation publicly available) are patient privacy-preserving as only summary statistics and regression coefficients are exchanged with the central server. A logistic regression model to predict post-treatment two-year survival was trained and evaluated by receiver operating characteristic curves (ROC), root mean square prediction error (RMSE) and calibration plots. Results In 4 months, we connected databases with 23 203 patient cases across 8 healthcare institutes in 5 countries (Amsterdam, Cardiff, Maastricht, Manchester, Nijmegen, Rome, Rotterdam, Shanghai) using the PHT. Summary statistics were computed across databases. A distributed logistic regression model predicting post-treatment two-year survival was trained on 14 810 patients treated between 1978 and 2011 and validated on 8 393 patients treated between 2012 and 2015. Conclusion The PHT infrastructure demonstrably overcomes patient privacy barriers to healthcare data sharing and enables fast data analyses across multiple institutes from different countries with different regulatory regimens. This infrastructure promotes global evidence-based medicine while prioritizing patient privacy

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Not Available

Not AvailableWe aimed towards investigating the effects of water deficit stress (WDS) on phenotypic traits, leaf gas exchange, water relations, secondary metabolite profile and fibre properties of six tossa jute (Corchorus olitorius) genotypes grown under control or water withholding conditions. Root length, root weight, stem weight and whole biomass were reduced significantly (p < 0.05) in susceptible genotypes but remain unaltered in tolerant genotypes following WDS. The tolerant genotypes showed significantly higher (p < 0.05) photosynthetic carbon assimilation (PCA) and water use efficiency (WUE) along with significant reduction (p < 0.05) in stomatal conductance (SC), transpiration rate (TR) and vapour pressure deficit (VPD) as compared to susceptible genotypes after WDS. Tolerant genotypes exhibited significantly higher (p < 0.05) % RWC as compared to susceptible plants following WDS. Polyphenol and flavonoid content were significantly increased (p < 0.05) in tolerant and susceptible genotypes respectively following WDS. Susceptible plants exhibited significantly reduced (p < 0.05) proline content as compared to tolerant genotypes. Number of phytochemotypes identified by GC–MS showed 46% and 81% increase in tolerant and susceptible groups respectively, after prolonged WDS. Major phytochemical groups in tolerant genotypes under WDS were ketone, acyclic diterpene alcohol, steroid/sterol, heterocyclic compound, alicyclic hydrocarbon, thiophenol and fatty acid ester. Whereas, the susceptible genotypes exhibited steroid/sterol, acyclic diterpene alcohol, alcohol and heterocyclic compound as the major phytochemical groups under WDS. Tolerant genotypes showed significantly higher (p < 0.05) fibre strength as compared to susceptible plants under stress. Our results show identifiable traits manifested by the tolerant and susceptible tossa jute genotypes under WDS which could therefore be utilized successfully for future selection and breeding programs, crop improvement initiatives and production of new varieties having optimum potential toward water deficit stress adaptation.Not Availabl

Nanoparticles and Nanomaterials-Based Recent Approaches in Upgraded Targeting and Management of Cancer: A Review

Along with the extensive improvement in tumor biology research and different therapeutic developments, cancer remains a dominant and deadly disease. Tumor heterogeneity, systemic toxicities, and drug resistance are major hurdles in cancer therapy. Chemotherapy, radiotherapy, phototherapy, and surgical therapy are some prominent areas of cancer treatment. During chemotherapy for cancer, chemotherapeutic agents are distributed all over the body and also damage normal cells. With advancements in nanotechnology, nanoparticles utilized in all major areas of cancer therapy offer the probability to advance drug solubility, and stability, extend drug half-lives in plasma, reduce off-target effects, and quintessence drugs at a target site. The present review compiles the use of different types of nanoparticles in frequently and recently applied therapeutics of cancer therapy. A recent area of cancer treatment includes cancer stem cell therapy, DNA/RNA-based immunomodulation therapy, alteration of the microenvironment, and cell membrane-mediated biomimetic approach. Biocompatibility and bioaccumulation of nanoparticles is the major impediment in nano-based therapy. More research is required to develop the next generation of nanotherapeutics with the incorporation of new molecular entities, such as kinase inhibitors, siRNA, mRNA, and gene editing. We assume that nanotherapeutics will dramatically improve patient survival, move the model of cancer treatment, and develop certainty in the foreseeable future

SOME RESULT ON COMMON FIXED POINT THEOREM FOR A PAIR OF ASYMPTOTICALLY NONEXPANSIVE MAPPINGS IN GENERALIZED S-CONVEX METRIC SPACE

ABSTRACT Let X be a generalized s-convex metric space, and let be a pair of asymptotically nonexpansive mappings. In this paper, we will consider an Ishikawa type iteration process with errors to approximate the unique common fixed point of Q and J. J Q

Magnetic resonance neurographic confirmation of extensive Plexiform neurofibroma in neurofibromatosis-1 presenting as ambiguous genitalia

Genitourinary involvement of neurofibromatosis is uncommon and genital neurofibromatosis is even rarer. Involvement of clitoris by neurofibroma can lead to clitoromegaly masquerading as a male penis. We report such a case of ambiguous genitalia in a 7-year-old female child presenting with clitoromegaly since birth, in which magnetic resonance imaging (MRI) revealed the presence of extensive neurofibromatosis in the clitoris and lumbosacral regions. We emphasize the central role of MRI in evaluation of hormonal and non-hormonal causes of ambiguous genitalia. We further discuss the merits of including MR neurography in the imaging protocol for comprehensive delineation of neurofibromatosis

Do phosphatase of regenerating liver-3, matrix metalloproteinases-2, matrix metalloproteinases-9, and epidermal growth factor receptor-1 predict response to therapy and survival in glioblastoma multiforme?

Context: Poor survival of the glioblastoma multiforme (GBM) has been attributed in part to the invasive nature of the lesion making complete surgical removal near impossible. Phosphatase of regenerating liver-3 (PRL-3), matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9), and epidermal growth factor receptor (EGFR-1) play a role in invasive nature of tumor cells. Aims: This study was conducted to evaluate PRL-3, MMP-2, MMP-9, and EGFR-1 (markers) expression in cases to GBM and to correlate their expression with therapy response and survival. Settings and Design: GBM cases (n = 62) underwent surgery followed by radiation (n = 34) and chemoradiation (n = 28). Using WHO Response Evaluation Criteria in Solid Tumors criteria response to therapy was assessed at 3 months and cases followed up for survival. Subjects and Methods: Expression of markers was assessed by immunohistochemistry as a percentage of positive tumor cells in hot spots. Statistical Analysis Used: Kaplan–Meier, ANOVA, Chi-square test, univariate, and multivariate Cox-regression analysis was done. Results: Response to therapy was evident in 54.8% cases of responders with the mean survival of 494.03 ± 201.13 days and 45.2% cases of non responders (278.32 ± 121.66 days) with P = 0.001. Mean survival for the patient's opted chemoradiation was 457.43 ± 222.48 days which was approximately 3 months greater than those who opted radiation alone (P = 0.029). We found PRL-3 overexpression was an independent, significant, poor prognostic factor for survival by multivariate analysis (P = 0.044). Cases negative for MMP's and EGFR showed increased survival, but the difference was insignificant. Conclusion: PRL-3 expression appears to be related to an adverse disease outcome