Management of B-cell lineage acute lymphoblastic leukemia: expert opinion from an Indian panel via Delphi consensus method

IntroductionCurrently, there are no guidelines for the management of B-cell lineage acute lymphoblastic leukemia (B-ALL) from an Indian perspective. The diagnostic workup, monitoring, and treatment of B-ALL vary among different physicians and institutes.ObjectiveTo develop evidence-based practical consensus recommendations for the management of B-ALL in Indian settings.MethodsModified Delphi consensus methodology was considered to arrive at a consensus. An expert scientific committee of 15 experts from India constituted the panel. Clinically relevant questions belonging to three major domains were drafted for presentation and discussion: (i) diagnosis and risk assignment; (ii) frontline treatment; and (iii) choice of therapy (optimal vs. real-world practice) in relapsed/refractory (R/R) settings. The questionnaire was shared with the panel members through an online survey platform. The level of consensus was categorized into high (≥ 80%), moderate (60%–79%), and no consensus (< 60%). The process involved 2 rounds of discussion and 3 rounds of Delphi survey. The questions that received near or no consensus were discussed during virtual meetings (Delphi rounds 1 and 2). The final draft of the consensus was emailed to the panel for final review.ResultsExperts recommended morphologic assessment of peripheral blood or bone marrow, flow cytometric immunophenotyping, and conventional cytogenetic analysis in the initial diagnostic workup. Berlin–Frankfurt–Münster (BFM)–based protocol is the preferred frontline therapy in pediatric and adolescent and young adult patients with B-ALL. BFM/German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia–based regimen is suggested in adult patients with B-ALL. Immunotherapy (blinatumomab or inotuzumab ozogamicin) followed by allogeneic hematopoietic cell transplantation (allo-HCT) is the optimal choice of therapy that would yield the best outcomes if offered in the first salvage in patients with R/R B-ALL. In patients with financial constraints or prior allo-HCT (real-world practice) at first relapse, standard-intensive chemotherapy followed by allo-HCT may be considered. For subsequent relapses, chimeric antigen receptor T-cell therapy or palliative care was suggested as the optimal choice of therapy.ConclusionThis expert consensus will offer guidance to oncologists/clinicians on the management of B-ALL in Indian settings

Catalytic ‘Gelectrodes’ for Sustainable and Enhanced Oxygen Evolution Reaction

Development of cost-effective catalysts providing low overpotentials and enhanced electrochemical kinetics is a critical goal of contemporary research on electrochemical water splitting and other technologically significant processes. Translation to practical applications demands that they should also enable high current densities to be extracted. A simple strategy of encapsulating the active electrocatalyst in hydrogel polymer matrices is shown to provide a facile solution in several respects, especially regarding the last criterion. The concept is illustrated using two examples of ‘gelectrodes’ based on nanocomposites of cobalt oxyhydroxide and nickel-iron hydroxide with chitosan on nickel foam, and their efficient mediation of the oxygen evolution reaction (OER). Comparison with control systems show that significantly lower overpotentials and higher current densities with extended temporal stability can be achieved with the gelectrodes; the cobalt oxyhydroxide - chitosan and nickel-iron hydroxide - chitosan systems provide stable current densities up to 1.6 - 1.7 A cm-2 for the OER with alkaline aqueous electrolyte. This simple design strategy opens up a general route to technologically useful electrocatalyst performance

Nanocarriers for stroke therapy : advances and obstacles in translating animal studies

The technology of drug delivery systems (DDS) has expanded into many applications, such as for treating neurological disorders. Nanoparticle DDS offer a unique strategy for targeted transport and improved outcomes of therapeutics. Stroke is likely to benefit from the emergence of this technology though clinical breakthroughs are yet to manifest. This review explores the recent advances in this field and provides insight on the trends, prospects and challenges of translating this technology to clinical application. Carriers of diverse material compositions are presented, with special focus on the surface properties and emphasis on the similarities and inconsistencies among in vivo experimental paradigms. Research attention is scattered among various nanoparticle DDS and various routes of drug administration, which expresses the lack of consistency among studies. Analysis of current literature reveals lipid- and polymer-based DDS as forerunners of DDS for stroke; however, cell membrane-derived vesicles (CMVs) possess the competitive edge due to their innate biocompatibility and superior efficacy. Conversely, inorganic and carbon-based DDS offer different functionalities as well as varied capacity for loading but suffer mainly from poor safety and general lack of investigation in this area. This review supports the existing literature by systematizing presently available data and accounting for the differences in drugs of choice, carrier types, animal models, intervention strategies and outcome parameters.Published versio

CEAT: Categorising Ethereum Addresses’ Transaction Behaviour with Ensemble Machine Learning Algorithms

Cryptocurrencies are rapidly growing and are increasingly accepted by major commercial vendors. However, along with their rising popularity, they have also become the go-to currency for illicit activities driven by the anonymity they provide. Cryptocurrencies such as the one on the Ethereum blockchain provide a way for entities to hide their real-world identities behind pseudonyms, also known as addresses. Hence, the purpose of this work is to uncover the level of anonymity in Ethereum by investigating multiclass classification models for Externally Owned Accounts (EOAs) of Ethereum. The researchers aim to achieve this by examining patterns of transaction activity associated with these addresses. Using a labelled Ethereum address dataset from Kaggle and the Ethereum crypto dataset by Google BigQuery, an address profiles dataset was compiled based on the transaction history of the addresses. The compiled dataset, consisting of 4371 samples, was used to tune and evaluate the Random Forest, Gradient Boosting and XGBoost classifier for predicting the category of the addresses. The best-performing model found for the problem was the XGBoost classifier, achieving an accuracy of 75.3% with a macro-averaged F1-Score of 0.689. Following closely was the Random Forest classifier, with an accuracy of 73.7% and a macro-averaged F1-Score of 0.641. Gradient Boosting came in last with 73% accuracy and a macro-averaged F1-Score of 0.659. Owing to the data limitations in this study, the overall scores of the best model were weaker in comparison to similar research, with the exception of precision, which scored slightly higher. Nevertheless, the results proved that it is possible to predict the category of an Ethereum wallet address such as Phish/Hack, Scamming, Exchange and ICO wallets based on its transaction behaviour

Automated analysis of pen-on-paper spirals for tremor detection, quantification, and differentiation

Objective: To develop an automated algorithm to detect, quantify, and differentiate between tremor using pen-on-paper spirals. Methods: Patients with essential tremor (n = 25), dystonic tremor (n = 25), Parkinson’s disease (n = 25), and healthy volunteers (HV, n = 25) drew free-hand spirals. The algorithm derived the mean deviation (MD) and tremor variability from scanned images. MD and tremor variability were compared with 1) the Bain and Findley scale, 2) the Fahn–Tolosa–Marin tremor rating scale (FTM–TRS), and 3) the peak power and total power of the accelerometer spectra. Inter and intra loop widths were computed to differentiate between the tremor. Results: MD was higher in the tremor group (48.9 ± 26.3) than in HV (26.4 ± 5.3; p < 0.001). The cut-off value of 30.3 had 80.9% sensitivity and 76.0% specificity for the detection of the tremor [area under the curve: 0.83; 95% confidence index (CI): 0.75, 0.91, p < 0.001]. MD correlated with the Bain and Findley ratings (rho = 0.491, p = 0 < 0.001), FTM–TRS part B (rho = 0.260, p = 0.032) and accelerometric measures of postural tremor (total power, rho = 0.366, p < 0.001; peak power, rho = 0.402, p < 0.001). Minimum Detectable Change was 19.9%. Inter loop width distinguished Parkinson’s disease spirals from dystonic tremor (p < 0.001, 95% CI: 54.6, 211.1), essential tremor (p = 0.003, 95% CI: 28.5, 184.9), or HV (p = 0.036, 95% CI: -160.4, -3.9). Conclusion: The automated analysis of pen-on-paper spirals generated robust variables to quantify the tremor and putative variables to distinguish them from each other. Significance: This technique maybe useful for epidemiological surveys and follow-up studies on tremor

Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia

Refractory acute myeloid leukemia (AML), defined as failure of two cycles of induction therapy at diagnosis or of one cycle at relapse, represents a subgroup with poor outcomes. Haploidentical natural killer cell (NK) therapy is a strategy that is being explored in refractory malignancies. Historically, at our center, patients with refractory AML have been treated with cytoreductive therapy (fludarabine + cytosine + granulocyte colony-stimulating factor ± idarubicin or mitoxantrone + etoposide) followed by 1-week rest and then reduced-intensity transplant with fludarabine + melphalan. We used the same backbone for this trial (CTRI/2019/02/017505) with the addition of CD56-positive cells from a family donor infused 1 day after the completion of chemotherapy. CD56-positive selection was done using a CliniMACS Prodigy system (Miltenyi Biotec, Bergisch Gladbach, Germany) followed by overnight incubation in autologous plasma with 2 micromolar arsenic trioxide and 500 U/mL of interleukin-2. From February 2019, 14 patients with a median age of 29 years (interquartile range [IQR]: 16.5–38.5) were enrolled in this trial. Six were females. Six had primary refractory AML while eight had relapsed refractory AML. The median CD56-cell dose infused was 46.16 × 106/kg (IQR: 25.06–70.36). One patient withdrew consent after NK cell infusion. Of the 13 patients who proceeded to transplant, five died of immediate post-transplant complications while two did not engraft but were in morphologic leukemia-free state (both subsequently died of infective complications after the second transplant). Of the remaining six patients who engrafted and survived beyond 1 month of the transplant, two developed disease relapse and died. The remaining four patients are alive and relapse free at the last follow-up (mean follow-up duration of surviving patients is 24 months). The 2-year estimated overall survival for the cohort was 28.6% ± 12.1% while the treatment-related mortality (TRM) with this approach was 38.5% ± 13.5%. Haploidentical NK cell therapy as an adjunct to transplant is safe and needs further exploration in patients with AML. For refractory AML, post-transplant NK infusion and strategies to reduce TRM while using pre-transplant NK infusion merit exploration

sj-jpg-6-cll-10.1177_09636897231198178 – Supplemental material for Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia

Supplemental material, sj-jpg-6-cll-10.1177_09636897231198178 for Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia by Uday Kulkarni, Arun Kumar Arunachalam, Hamenth Kumar Palani, Reeshma Radhakrishnan Nair, Nithya Balasundaram, Arvind Venkatraman, Anu Korula, Sushil Selvarajan, Sharon Lionel, Poonkuzhali Balasubramanian, Madhavi Maddali, Aby Abraham, Biju George and Vikram Mathews in Cell Transplantation</p