A national survey of current immunohematologic testing practices for the diagnosis of autoimmune hemolytic anemia in India.

Autoimmune hemolytic anemia (AIHA) is a common term for several disorders that differ from one another in terms of etiology, pathogenesis, clinical features, and treatment. Management of patients with AIHA has become increasingly evidence-based in recent years. While this development has resulted in therapeutic improvements, it also carries increased requirements for optimal diagnosis using more advanced laboratory tests. Unfortunately, limited data are available from developing countries regarding the testing and transfusion management of patients with AIHA. The main objective of this survey was to explore the current immunohematologic testing practices for the diagnosis of AIHA in India. This online survey consisted of 30 questions, covering the place of work, the number of AIHA cases encountered in the 3 preceding years, testing method(s), transfusion management, and so forth. Individuals representing 89 laboratories completed the survey; only 78 of which responded that AIHA testing was performed in their facility's laboratory. The majority of respondents agreed that the most commonly affected age-group comprised individuals of older than 20 years, with a female preponderance. Regarding transfusion management, respondents indicated that transfusion with "best-match" red blood cell units remains the most common practice. Column-agglutination technology is used by 92 percent of respondents as the primary testing method. Although a monospecific direct antiglobulin test is available at 73 percent of the sites, most of them have limited access to other resources that could diagnose cold or mixed AIHA. Merely 49 percent of responding laboratories have the resources to perform adsorption studies for the detection of alloantibodies. Furthermore, three-cell antibody screening reagents are unavailable at 32 percent of laboratories. In 72 percent of centers, clinical hematologists would prefer to consult a transfusion medicine specialist before administering treatment to AIHA patients. There is unanimous agreement regarding the need for a national registry. The survey data indicate wide variability in testing practices for patients with AIHA in India. Future studies are needed to focus on the feasibility and cost-effectiveness of different testing strategies for developing countries.

E-learning in transfusion medicine: An exploratory qualitative assessment.

BACKGROUND AND OBJECTIVES: E-learning programmes are increasingly offered in transfusion medicine (TM) education. The aim of this study was to explore facilitators and barriers to TM e-learning programmes, including assessment of learning outcomes and measures of effectiveness. MATERIALS AND METHODS: Participants selected from a prior survey and representing a diverse number of international e-learning programmes were invited to participate. A mixed methodology was employed, combining a survey and individual semi-structured one-on-one interviews. Interview data were analysed inductively to explore programme development, evaluation, and facilitators and barriers to implementation. RESULTS: Fourteen participants representing 13 institutions participated in the survey and 10 were interviewed. The e-learning programmes have been in use for a variable duration between 5 and 16 years. Funding sources varied, including government and institutional support. Learner assessment methods varied and encompassed multiple-choice-questions (n = 12), direct observation (n = 4) and competency assessment (n = 4). Most regional and national blood collection agencies rely on user feedback and short-term learning assessments to evaluate their programmes. Only one respondent indicated an attempt to correlate e-learning with clinical practices. Factors that facilitated programme implementation included support from management and external audits to ensure compliance with regulatory educational and training requirements. Barriers to programme implementation included the allocation of staff time for in-house development, enforcing compliance, keeping educational content up-to-date and gaining access to outcome data for educational providers. CONCLUSION: There is evidence of considerable diversity in the evaluation of e-learning programmes. Further work is needed to understand the ultimate impact of TM e-learning on transfusion practices and patient outcomes.

Entanglement monogamy in indistinguishable particle systems.

Recently, it has been realized that indistinguishability is a resource for quantum information processing. A new method to represent the indistinguishable particles by Franco et al. (Sci Rep 6:20603, 2016, https://doi.org/10.1038/srep20603 ) and measure the concurrence is developed by Nosrati et al. (npj Quantum Inf 6:39, 2020, https://doi.org/10.1038/s41534-020-0271-7 ). The monogamy property says that quantum entanglement cannot be shared freely between more than two particles. For three distinguishable particles, the monogamy of entanglement was first expressed as an inequality using squared concurrence where each particle has a single degree of freedom (for pure or mixed states). Using multiple degrees of freedom, similar inequality was shown to be held between two distinguishable particles. However, for two indistinguishable particles, where each particle cannot be addressed individually, the monogamy inequality was shown to be violated maximally for a specific state. Thus a question naturally arises: what happens to the monogamy of entanglement in the case of three or more indistinguishable particles? We prove that monogamy holds in this scenario and the inequality becomes equality for all pure indistinguishable states. Further, we provide three major operational meanings of our result. Finally, we present an experimental schematic using photons to observe our result.

Bioactive Metabolites of Serratia sp. NhPB1 Isolated from Pitcher of Nepenthes and its Application to Control Pythium aphanidermatum.

Plant-associated bacteria have already been considered as the store house of bioactive compounds that confer the plant growth promotion and disease protection. Hence, the unique plant parts have already been expected to harbor diverse microbial communities with multi-beneficial properties. Based on this, the current study has been designed to identify the potential of Serratia sp. NhPB1 isolated from the pitcher of Nepenthes plant for its activity against the infamous pathogen Pythium aphanidermatum. The in vitro antifungal, plant growth promoting and enzymatic activities of the isolate indicated its promises for agricultural application. The isolate NhPB1 was also demonstrated to have positive effect on Solanum lycopersicum and Capsicum annuum, due to its plant beneficial metabolites. From the results of LC-MS/MS analysis, the isolate has also been revealed to have the ability to synthesize bioactive compounds including salicylic acid, cyclodipeptides, acyl homoserine lactone, indole-3-acetic acid, and serrawettin W1. These identified compounds and their known biological properties make the isolate characterized in the study to have significant promises as an eco-friendly solution for the improvement of agricultural productivity.

Instabilities near Ultrastrong Coupling in a Microwave Optomechanical Cavity.

With artificially engineered systems, it is now possible to realize the coherent interaction rate, which can become comparable to the mode frequencies, a regime known as ultrastrong coupling (USC). We experimentally realize a cavity-electromechanical device using a superconducting waveguide cavity and a mechanical resonator. In the presence of a strong pump, the mechanical-polaritons splitting can nearly reach 81% of the mechanical frequency, overwhelming all the dissipation rates. Approaching the USC limit, the steady-state response becomes unstable. We systematically measure the boundary of the unstable response while varying the pump parameters. The unstable dynamics display rich phases, such as self-induced oscillations, period-doubling bifurcation, and period-tripling oscillations, ultimately leading to the chaotic behavior. The experimental results and their theoretical modeling suggest the importance of residual nonlinear interaction terms in the weak-dissipative regime.

Multi-Omics Pipeline and Omics-Integration Approach to Decipher Plant's Abiotic Stress Tolerance Responses.

The present day's ongoing global warming and climate change adversely affect plants through imposing environmental (abiotic) stresses and disease pressure. The major abiotic factors such as drought, heat, cold, salinity, etc., hamper a plant's innate growth and development, resulting in reduced yield and quality, with the possibility of undesired traits. In the 21st century, the advent of high-throughput sequencing tools, state-of-the-art biotechnological techniques and bioinformatic analyzing pipelines led to the easy characterization of plant traits for abiotic stress response and tolerance mechanisms by applying the 'omics' toolbox. Panomics pipeline including genomics, transcriptomics, proteomics, metabolomics, epigenomics, proteogenomics, interactomics, ionomics, phenomics, etc., have become very handy nowadays. This is important to produce climate-smart future crops with a proper understanding of the molecular mechanisms of abiotic stress responses by the plant's genes, transcripts, proteins, epigenome, cellular metabolic circuits and resultant phenotype. Instead of mono-omics, two or more (hence 'multi-omics') integrated-omics approaches can decipher the plant's abiotic stress tolerance response very well. Multi-omics-characterized plants can be used as potent genetic resources to incorporate into the future breeding program. For the practical utility of crop improvement, multi-omics approaches for particular abiotic stress tolerance can be combined with genome-assisted breeding (GAB) by being pyramided with improved crop yield, food quality and associated agronomic traits and can open a new era of omics-assisted breeding. Thus, multi-omics pipelines together are able to decipher molecular processes, biomarkers, targets for genetic engineering, regulatory networks and precision agriculture solutions for a crop's variable abiotic stress tolerance to ensure food security under changing environmental circumstances.

Topological data analysis of human brain networks through order statistics.

Understanding the common topological characteristics of the human brain network across a population is central to understanding brain functions. The abstraction of human connectome as a graph has been pivotal in gaining insights on the topological properties of the brain network. The development of group-level statistical inference procedures in brain graphs while accounting for the heterogeneity and randomness still remains a difficult task. In this study, we develop a robust statistical framework based on persistent homology using the order statistics for analyzing brain networks. The use of order statistics greatly simplifies the computation of the persistent barcodes. We validate the proposed methods using comprehensive simulation studies and subsequently apply to the resting-state functional magnetic resonance images. We found a statistically significant topological difference between the male and female brain networks.

9-Tricosene Containing Blend of Volatiles Produced by Serratia sp. NhPB1 Isolated from the Pitcher Plant Provide Plant Protection Against Pythium aphanidermatum.

Plant-associated bacteria exhibit diverse chemical means to protect plants from the pathogens. The present study has been conducted to evaluate the volatile-mediated antifungal activity of Serratia sp. NhPB1 isolated from the pitcher plant against the notorious pathogen Pythium aphanidermatum. The study has also evaluated the protective effect of NhPB1 on Solanum lycopersicum and Capsicum annuum leaves and fruits against P. aphanidermatum. From the results, NhPB1 was found to have remarkable activity against the tested pathogen. The isolate was also found to impart disease protection in selected plants as evidenced by the morphological changes. Here, the leaves and fruits of S. lycopersicum and C. annuum control which were treated with the uninoculated LB and distilled water were found to have the presence of P. aphanidermatum growth with lesions and decaying of tissues. However, the NhPB1-treated plants did not show any symptoms of fungal infection. This could further be confirmed by the microscopical examination of tissues by propidium iodide staining. Here, the normal architecture of leaf and fruit tissues could be observed in the NhPB1-treated group, but the tissue invasion by P. aphanidermatum was observed in the control group which further confirms the promises of selected bacteria for biocontrol applications.

Real-world data from India on clinical practices in the management of autoimmune haemolytic anaemia: A survey-based cross-sectional assessment.

BACKGROUND: Autoimmune haemolytic anaemia (AIHA) is a decompensated acquired haemolysis caused by the host's immune system acting against its own red cell antigens. The aim of this national survey is to capture real-world data of clinical practices in AIHA by collecting responses from clinical haematologists across India. METHODOLOGY: In this cross-sectional study, a structured, 26-question online survey was conducted in India by few members of the special interest group in immunohaematology between January and March, 2022. The final survey consisted of questions covering place of work, amount of AIHA cases being evaluated by the haematologist over preceding years, basic demographic, clinical and laboratory features of the patients being treated under them etc. Descriptive statistical analysis was performed during the assessment. RESULTS: The survey response rate was 48.2% (53/110), 69.8% (37/53) have diagnosed and managed more than 10 AIHA cases in the last 3 years with a female preponderance. There was considerable variability in response. While 56.6% (30/53) of respondents do have the access to the facilities to subtype AIHA cases; 32.1% (17/53) of clinicians would prefer administering high dose steroids for 6 weeks or more in non-responding patients, and only 45.3% (24/53) would assess the risks of thrombosis in AIHA. There is unanimous agreement among the participants that health-related quality of life should be taken into consideration in patients and the need for a national registry of patients with AIHA in India. CONCLUSION: The current national survey showed that some aspects of AIHA management were consistent; others were less so, but also significant variations were observed in certain clinical practices, where the evidence base is limited. A joint effort is needed to establish a national patient registry by including both clinical haematologists and transfusion medicine specialists which could potentially standardise AIHA management and future research in India.

An early Indian experience with benralizumab - A compendium on severe asthma cases: a case series.

Background: Severe eosinophilic asthma (SEA), one of the phenotypes of asthma that is characterized by elevated blood eosinophil counts, is a common cause of uncontrolled asthma. Patients with SEA often experience severe persistent symptoms and have frequent exacerbations despite optimal inhaler therapy. They also have poor lung function and quality of life (QoL). Benralizumab (Fasenra), a monoclonal antibody, has been approved for managing cases of SEA. This series of six cases, the first of its kind from India, aims to add to the real-world evidence of benralizumab in India. Methods: Benralizumab 30 mg (once in four weeks for the first three doses followed by a dose every eight weeks for two years) was administered in six patients with symptoms of cough, breathlessness on exertion, and wheezing, diagnosed with SEA. The following were the endpoints assessed: (i) overlap between high immunoglobulin E (IgE) and eosinophilic asthma; (ii) reduction of exacerbations; (iii) withdrawal of oral corticosteroids; and (iv) improvement in lung function and QoL. Results: In all cases, management with benralizumab resulted in optimal clinical and functional improvement, a decline in systemic steroid use, and improved QoL. Conclusions: The cases presented here are the first of their kind in the Indian asthmatic population with all SEA patients demonstrating significant improvement in symptoms with the use of benralizumab.

Plerixafor use in autologous hematopoietic stem cell mobilization: Experience from a single center in Southern India.

BACKGROUND: Plerixafor is used for patients at risk of Stem cell mobilization failure based on clinical factors or low peripheral blood CD34 count. It is also added upfront to any mobilization irrespective of risk factor, but the cost-effectiveness of the approach is an issue. Data on plerixafor in different settings of autologous hematopoietic stem cell (HSC) collection from India are scant. We are hereby reporting the experience of failure/success of mobilization rate and few important significant variables (CD34+ dosage, failed collection) between plerixafor and granulocyte colony-stimulating factor alone groups among autologous hematopoietic stem cell transplantation (aHSCT) at our institute. METHODS: This was a record-based single-center study on patients who underwent aHSCT from January 2013 to June 2019 at a tertiary care hospital. Descriptive statistics were used for baseline characteristics, transplant-related factors, and peritransplant outcomes. All statistical analyses were performed at the 5% significance level. RESULTS: During the study duration, a total of 96 patients had undergone autologous hematopoietic stem cell collection (aHSCC), all by peripheral blood stem cell harvest, requiring 131 apheretic collections. Of the total 131 collections in 96 patients, plerixafor was used in 63 apheresis collections (48% of total pheresis) in 40 patients. Among the 40 patients who were administered plerixafor to augment the collection, 34 patients had upfront use of plerixafor. We did not observe any significant adverse event related to plerixafor use. CONCLUSION: A rational utilization of plerixafor can facilitate the process and logistics of aHSCC outcome.

E-learning/online education in transfusion medicine: A cross-sectional international survey.

OBJECTIVES: This survey aims to assess the scope of transfusion e-learning courses in blood establishments and transfusion services internationally. BACKGROUND: E-learning/online education is increasingly used in the education of medical professionals. There is limited published data on the use of e-learning for transfusion medicine. MATERIAL AND METHODS: An International survey was designed and distributed to all members of the International Society of Blood Transfusion to assess utilisation of e-learning in their institutions. Descriptive statistics were used to summarise the results. RESULTS: A total of 177 respondents participated, 68 of which had e-learning modules in their institutions. Approximately two-thirds of the courses were developed in-house (66%), and 63% are available to learners from outside the host institutions. In one-third of institutions, these courses were established during the COVID-19 pandemic, while 15% had used e-learning courses for more than 10 years. The courses target different audiences and topics ranging from blood donation to hemovigilance. The most common audiences were physicians (71%), laboratory scientists/technologists (69%) and transfusion practitioners (63%). Formal assessment of learning outcomes is used in 70% of the programs. CONCLUSIONS: The survey demonstrates the widespread use of e-learning courses in transfusion education, with a substantial proportion being developed during the COVID-19 pandemic.

Red blood cell alloimmunization among recipients of blood transfusion in India: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: There is a varied prevalence of red cell alloimmunization being reported from different parts of India. This study aimed to estimate the overall prevalence of alloimmunization in India by performing a systematic review of the literature and to establish the most suitable antigen-matching strategy to reduce the red blood cell (RBC) alloimmunization rate among transfusion recipients. MATERIALS AND METHODS: A systematic search of all the original articles published in English on RBC alloimmunization among transfusion recipients from India in MEDLINE, SCOPUS, CINAHL and Google Scholar bibliographic databases was conducted. After screening the articles as per inclusion/exclusion criteria, data extraction was done independently by two sets of investigators. Meta-analysis was performed by the binary random-effects model using the restricted maximum likelihood method. RESULTS: A total of 44 studies on RBC alloimmunization, with a cumulative sample size of 309,986 patients, were grouped into hospital-based and multiply-transfused patients, which yielded a prevalence of 0.5 (95% confidence interval; 0.3-0.8) and 4.8 (95% confidence interval; 3.9-5.7) per 100 patients, respectively. As many as 1992 alloantibodies were identified among the 1846 alloimmunized patients. The most common antibody identified was anti-E (127; 31.99%), followed by anti-c (75; 18.89%) in multiply-transfused patients. CONCLUSION: The rate of alloimmunization was 0.5 per 100 patients tested for antibodies and 4.8 per 100 patients receiving transfusion. Considering E- and c-antigen-matched red cells along with ABO and RhD matching may significantly reduce the overall occurrence of alloimmunization among Indian population who are transfusion-dependent.

Light-Induced Hypoxia in Carbon Quantum Dots and Ultrahigh Photocatalytic Efficiency.

Carbon quantum dots (CQDs) represent a class of carbon materials exhibiting photoresponse and many potential applications. Here, we present a unique property that dissolved CQDs capture large amounts of molecular oxygen from the air, the quantity of which can be controlled by light irradiation. The O2 content can be varied between a remarkable 1 wt % of the CQDs in the dark to nearly half of it under illumination, in a reversible manner. Moreover, O2 depletion enhances away from the air-solution interface as the nearby CQDs quickly regain them from the air, creating a pronounced concentration gradient in the solution. We elucidate the role of the CQD functional groups and show that excitons generated under light are responsible for their tunable adsorbed-oxygen content. Because of O2 enrichment, the photocatalytic efficiency of the CQDs toward oxidation of benzylamines in the air is the same as under oxygen flow and far higher than the existing photocatalysts. The findings should encourage the development of a new class of oxygen-enricher materials and air as a sustainable oxidant in chemical transformations.

Experience with mepolizumab in adults with severe eosinophilic asthma: a case series from India.

Severe asthma can be associated with eosinophilic or allergic phenotypes or both. Eosinophilic inflammation is associated with exacerbations and disease severity due to biological activity of interleukin-5 (IL-5). Patients with severe asthma have reported reduced lung function and poor health-related quality of life (HRQoL) and may require systemic corticosteroids for its management. Thus, treatment targeting IL-5 can help improve quality of life and reduce the use of systemic corticosteroids in severe asthma. Mepolizumab is approved for treating severe eosinophilic asthma as it helps reduce exacerbations, improve lung function and asthma control, and reduce the use of systemic glucocorticoids. This further helps in enhancing HRQoL of these patients. This case series includes four adult patients suffering from severe eosinophilic asthma who were treated with mepolizumab.

Cocktail Protocol for Preparation of Platelet-Rich Fibrin Glue for Autologous Use.

BACKGROUND: Biomaterials containing platelets have been used to promote healing of ulcers and burns, as well as in implantology and maxillofacial and plastic surgery to achieve wound healing and tissue repair. Commercial devices to prepare autologous biomaterials involve diverse preparation methods that can have high production costs and low yields. Hence, we designed a protocol for preparation of large amounts of autologous platelet-rich fibrin (PRF) glue using conventional processing techniques for blood components. METHODS: Autologous whole blood collected 72 h before surgery was processed to prepare platelet concentrates and cryoprecipitate. In a closed system, calcium was added to the cryoprecipitate to release autologous thrombin and generate a firm fibrin clot. The fibrin clot, platelets and calcium were then placed in a conical flask in which a PRF glue formed. The protocol was validated through determination of pre- and post-platelet counts and fibrinogen amounts in the product. RESULTS: Platelets were recovered with 68% efficiency during the preparation. Essentially no platelets or fibrinogen were found in the supernatant of the PRF glue, suggesting that nearly all had been incorporated in a PRF glue having a relatively large (8 cm × 10 cm) size. CONCLUSION: The protocol described here is a cost-effective, simple and closed system that can be used to produce large-size PRF glue to promote repair of major surgical defects.

Genome sequencing and annotation of multi-virulent Aeromonas veronii XhG1.2 isolated from diseased Xiphophorus hellerii.

The present study was intended to elucidate the genomic basis of antibiotic resistance and hyper-virulence of the fish pathogen Aeromonas veronii XhG1.2 characterized in our previous work. The identity of XhG1.2 was confirmed through 16S rDNA sequence analysis and whole genome sequence analysis. The top-hit species distribution analysis of XhG1.2 sequence data revealed major hits against the Aeromonas veronii. The identification of virulence genes using the VFDB showed the genome of XhG1.2 to have the genes coding for the virulence factors viz. aerolysin, RtxA, T2SS, T3SS and T6SS. The presence of antibiotic resistance predicted through the CARD database analysis showed it to have the CephA3, OXA-12, adeF and pulvomycin resistance genes. By the phylogenetic and comparative genomic analysis, A. veronii species were found to have genes for toxin production. This also confirmed the pathogenicity and drug resistance of A. veronii XhG1.2 and also its potential to cause disease in diverse ornamental fishes.

Clinical Implication of Immunohaematological Tests in ABO haemolytic disease of newborn: Revisiting an old disease.

OBJECTIVE: We aimed to assess the frequency distribution of of ABO haemolytic disease of newborn (ABO-HDN) and to know the predictive value of immunohaematological tests in identifying at risk neonates. BACKGROUND: ABO incompatibility, although a common cause of haemolytic disease of newborn, has several unaddressed issues related to it. MATERIAL AND METHODS: A prospective study over 20 months was carried out in a tertiary care centre in South India. Blood grouping, Direct Antiglobulin test (DAT) and elution studies were performed on neonatal samples, whereas blood grouping, antibody screening and antibody titration were performed on maternal samples. In suspected cases, ABO-HDN was diagnosed after excluding other possible causes for haemolysis. The laboratory results were correlated with the clinical details to assess the predictive value of the tests. RESULTS: Of the total 2856 pregnancies, 34% had ABO incompatibility. On testing with columnagglutination test (CAT), the overall DAT positivity and that among ABO-incompatible cases were 3.8% and 11.2%, respectively,) whereas by conventinal tube technique (CTT) it was 0.6% and 2.4% respectively. CAT was found to have higher sensitivity, and the predictive value was higher for CTT. Maternal IgG titre showed a positive linear relationship with the DAT strength and the rise in indirect bilirubin levels. The positive predictive value of combination of tests such as DAT, elution and titation was 94.12%, which was much higher than that of the individual tests. CONCLUSION: DAT positivity is a predictor of early rise in serum bilirubin level, and a combination of tests has a better predictive value than individual tests towards development of clinically significant hyperbilirubinemia in ABO-HDN.