Unlocking The Mysteries of DNA Adducts with Artificial Intelligence.

Cellular genome is considered a dynamic blueprint of a cell since it encodes genetic information that gets temporally altered due to various endogenous and exogenous insults. Largely, the extent of genomic dynamicity is controlled by the trade-off between DNA repair processes and the genotoxic potential of the causative agent (genotoxins or potential carcinogens). A subset of genotoxins form DNA adducts by covalently binding to the cellular DNA, triggering structural or functional changes that lead to significant alterations in cellular processes via genetic (e. g., mutations) or non-genetic (e. g., epigenome) routes. Identification, quantification, and characterization of DNA adducts are indispensable for their comprehensive understanding and could expedite the ongoing efforts in predicting carcinogenicity and their mode of action. In this review, we elaborate on using Artificial Intelligence (AI)-based modeling in adducts biology and present multiple computational strategies to gain advancements in decoding DNA adducts. The proposed AI-based strategies encompass predictive modeling for adduct formation via metabolic activation, novel adducts' identification, prediction of biochemical routes for adduct formation, adducts' half-life predictions within biological ecosystems, and, establishing methods to predict the link between adducts chemistry and its location within the genomic DNA. In summary, we discuss some futuristic AI-based approaches in DNA adduct biology.

Evaluation of new non-invasive & conventional invasive methods of haemoglobin estimation in blood donors.

Background & objectives: The non-invasive method of haemoglobin (Hb) estimation has unique advantages of exemption of finger prick and associated pain, over invasive methods. This study was done to compare invasive and non-invasive methods of Hb estimation in blood donors keeping haematology analyzer (HA) as a reference method. Methods: The blood donors selected or deferred on the basis of CuSO4method (Hb ≥12.5 g/dl), were included in the study. Hb values of the donors were estimated by HemoCue and then by OrSense methods. An immediate post-donation venous sample was drawn for analysis on HA. Results: The mean Hb value was 13.98±1.27 g/dl on HA, 14.87±1.03 g/dl on OrSense and 15.03±1.31 g/dl on HemoCue. CuSO4, HemoCue and OrSense demonstrated sensitivities of 18.7, 18.7 and 13.1 per cent, positive predictive values (PPV) of 64.5, 83.3 and 60.9 per cent and specificities of 98.9, 99.6 and 99.1 per cent, respectively. The intra-class correlation coefficient for OrSense was 0.726 while that for HemoCue was 0.851. Bland-Altman plots demonstrated 2SD difference of >2.0 g/dl in Hb estimations between HA and HemoCue/OrSense. Interpretation & conclusions: The non-invasive modality may provide the near-ideal pre-donation Hb screening platform if an improvement can be done in the sensitivity and PPV of the non-invasive method keeping in view its unique advantages.

Discrepancy in Blood Grouping: Subgroups of B-Challenges and Dilemma.

Though not very frequent, blood group discrepancies are of common occurrence which must be promptly resolved for safe transfusion practices. Blood group discrepancy is defined as the non-corroboration between cell grouping and serum grouping. Variable erythrocyte antigenic expressions (qualitative and/or quantitative difference) owing to allelic heterogeneity, give rise to subgroups. Problems during blood grouping due to weakened expression of antigens are a rare cause for ABO discrepancies. Of note, subgroups of 'B' with decreased expression of the B antigen are of very rare occurrence in the general population. Serologically, the variants of 'B' can be classified into B3, Bx, Bm and Bel. Serological confirmation of such subgroups requires special immuno-haematological procedures. The current study reports 3 cases of subgroups of B (2 cases of Bm and 1 case of Bw) detected at our centre. It is important to detect and resolve discrepant ABO grouping results so as to prevent ABO mis-match transfusions. Such individuals should also be pre-emptively informed of their respective blood donor and transfusion recipient status, as well.

Low-density lipoprotein apheresis in a pediatric patient of familial hypercholesterolemia: Primi experientia from a tertiary care center in North India.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder due to mutation of apolipoprotein-B receptor gene causing severe dyslipidemia. Lifestyle modification and medical treatment attenuate the disease progression, but as these fail to control the blood cholesterol levels, low-density lipoprotein (LDL) apheresis comes forth as a treatment option. To the best of our knowledge, the following is the very first case of pediatric FH being treated by LDL-apheresis to be reported from India. A severely malnourished female child presented with yellowish skin lesions over different parts of the body, viz., bilateral Achilles tendon, both knees, elbows, both pinnae, and outer canthus of both eyes. She had a strong family history of borderline hypercholesterolemia and was diagnosed as a case of FH. She was maintained on diet modification. LDL-apheresis was planned as the cholesterol levels were not controlled with the diet modificationt. However, unavailability of an appropriate kit in India for LDL-apheresis led to the use of the modified PL1 kit meant for therapeutic plasma exchange procedures. We conducted two sessions of LDL-apheresis. After the first session, the LDL-cholesterol (LDL-C) level fell by 75.9% and the total cholesterol fell by 73.5%. A second procedure led to a decline in total cholesterol level by 18.6% and LDL-C by 19.46%. Subsequently, she was advised diet modification and statin therapy with regular follow-up after every 6 months. Thus, the cascade filtration technique is a safe and effective treatment option for removing the undesired lipoproteins.

Adverse Events During Apheresis Procedures: Audit at a Tertiary Hospital.

Apheretic platelets are better quality blood components which reduce donor exposure and chances of TTIs to transfusion recipients when compared to the whole blood derived components. Though safe, these apheretic donations are associated with donor adverse events. We evaluated the incidence of such adverse events associated with the modern apheresis procedures that would provide an insight as well as help formulating preventive steps to avoid frequent occurrences of such events. This prospective audit-based observational study was conducted over 1 year. Donors for plateletpheresis were selected as per the standard operating procedure of the Apheresis Lab. The apheresis procedures were done on the MCS+ (Haemonetics Corp.), Trima Accel (Terumo BCT) and COM.TEC (Fresenius Kabi AG). 1740 apheresis procedures were performed, out of which 1708 were plateletpheresis and 32 therapeutic plasma exchange (TPE) procedures for 7 patients. A total of 102 adverse events were noted; of which, 80 (78.43 %) events were associated with donors, 15 (14.71 %) were owed to equipment related problems and 7 (6.86 %) were technical aberrations. All the events associated with donors were mild. No adverse events were reported with any of the 32 TPEs. Apheresis procedures are associated with adverse events which can be reduced by meticulous donor-vigilance, superior training modules for the technical personnel and continued supervision of experienced transfusion medicine specialists. Continued efforts towards making the donor's experience with apheresis more pleasant give a forward thrust to the noble vision of preparing a voluntary apheresis donor pool in India.

Evaluation of Mirasol pathogen reduction system by artificially contaminating platelet concentrates with Staphylococcus epidermidis: A pilot study from India.

BACKGROUND AND OBJECTIVES: This study was conducted to assess the efficacy of Mirasol pathogen reduction system for platelets aimed at preventing bacterial regrowth by spiking buffy coat pooled platelets (BCPP) with clinically relevant load of Staphylococous epidermidis. MATERIALS AND METHODS: BCPP units were prepared using Teruflex BP-kit with Imugard III-S-PL (Terumo BCT, Tokyo, Japan). Two BCPP units were pooled, of which 40 ml of negative control (NC) was removed. The remaining volume of the platelet unit was inoculated with clinically relevant load of bacteria (total of 30 CFU of S. epidermidis in 1 ml); following this the platelet unit was split into two parts. One part served as positive control (PC) and the other part was subjected to pathogen reduction technique (Mirasol PRT, CaridianBCT Biotechnologies, Lakewood, CO, USA). Bacterial detection was performed using BacT/ALERT system, controls after day 1 and day 7 following inoculation of bacteria and on day 7 for Mirasol-treated unit. RESULTS: Of the 32 treatment cycles, 28 were valid and 4 were invalid. No regrowth was observed in 96.4% (27 of 28) after treatment with Mirasol pathogen reduction system. Of four invalid tests, on two instances the NC showed growth, whereas in other 2 no regrowth was detected in 7(th) day PC. Bacterial screening of PCs by BacT/ALERT after 24 h of incubation was 28.6%, whereas the effectiveness increased to 100% when incubated for 7 days. CONCLUSIONS: Mirasol system was effective in inactivating S. epidermidis when it was deliberately inoculated into BCPP at clinically relevant concentrations. Such systems may significantly improve blood safety by inactivating traditional and emerging transfusion-transmitted pathogens.

Comparison of Procleix Ultrio Elite and Procleix Ultrio NAT Assays for Screening of Transfusion Transmitted Infections among Blood Donors in India.

Background. Introduction of nucleic acid testing (NAT) has helped in decreasing window period donations, resulting in increased safety of blood supplies. NAT combines the advantages of direct and highly sequence-specific detection of viral genomes. We analysed the performance of newer Procleix Ultrio Elite (PUE) and Procleix Ultrio assay (PUA) for the screening of the viral markers in our donor population. Material and Methods. 10,015 donor samples were screened by routine immunoassays and both versions of NAT. NAT yields detected were subjected to viral load estimation and to other serological markers. Results. A total of 21 NAT yields were detected; three were positive by both NAT systems, whereas 18 samples were reactive by PUE only. NAT yields include 18 HBV and 3 HCV yields, of which 17 HBV yields were occult infections and 1 was window period (WP) infection. All 3 HCV yields were WP infections. No HIV-1/HIV-2 yield was found. Conclusion. Efficient target capture chemistry in the new TMA assay version significantly improved sensitivity. NAT is superior to serological immunoassays for screening of the viral markers; and the efficient target capture system in the newer TMA assay, namely, the PUE system, has significantly improved sensitivity over the earlier versions.