Adverse Drug Reaction Monitoring of Anticancer Drugs in Hematology Department

Background: Cancer is among the leading causes of mortality in India. Studies have reported antineoplastic agents as the common class of drugs causing Adverse Drug Reactions (ADRs). The present study aimed to conduct active surveillance of ADRs of anticancer drugs in the hematology department.Methods: A prospective observational study was conducted in 136 patients with cancer and the incidence and frequency of ADRs were assessed. The study was conducted in 6 months in a multispecialty hospital.Results: Among 136 cancer patients, All was more prevalent (39.70%); CLL, Non- Hodgkin’s Lymphoma were less prevalent (0.73%). ADRs were more prevalent in the Pediatrics department, i.e., 18.53% of ADRs were observed in patients aged <10 years. ADRs in male patients constituted 54.39%, whereas it was 45.60% in female patients. Cytarabine caused the highest number of ADRs (34.48%). The most prevalent ADR was anemia (25.60%).Conclusion: Multiple ADRs were detected in cancer patients. We found that hematological ADRs were more prevalent. Most of the ADRs were possible reactions according to Naranjo and the World Health Organization (WHO) scales

Preclinical Analysis of JAA-F11, a Specific Anti-Thomsen-Friedenreich Antibody via Immunohistochemistry and In Vivo Imaging.

The tumor specificity of JAA-F11, a novel monoclonal antibody specific for the Thomsen-Friedenreich cancer antigen (TF-Ag-alpha linked), has been comprehensively studied by in vitro immunohistochemical (IHC) staining of human tumor and normal tissue microarrays and in vivo biodistribution and imaging by micro-positron emission tomography imaging in breast and lung tumor models in mice. The IHC analysis detailed herein is the comprehensive biological analysis of the tumor specificity of JAA-F11 antibody performed as JAA-F11 is progressing towards preclinical safety testing and clinical trials. Wide tumor reactivity of JAA-F11, relative to the matched mouse IgG3 (control), was observed in 85% of 1269 cases of breast, lung, prostate, colon, bladder, and ovarian cancer. Staining on tissues from breast cancer cases was similar regardless of hormonal or Her2 status, and this is particularly important in finding a target on the currently untargetable triple-negative breast cancer subtype. Humanization of JAA-F11 was recently carried out as explained in a companion paper "Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and In Vitro Efficacy Analysis" (Neoplasia 19: 716-733, 2017), and it was confirmed that humanization did not affect chemical specificity. IHC studies with humanized JAA-F11 showed similar binding to human breast tumor tissues. In vivo imaging and biodistribution studies in a mouse syngeneic breast cancer model and in a mouse-human xenograft lung cancer model with humanized 124I- JAA-F11 construct confirmed in vitro tumor reactivity and specificity. In conclusion, the tumor reactivity of JAA-F11 supports the continued development of JAA-F11 as a targeted cancer therapeutic for multiple cancers, including those with unmet need

Knowledge, attitude and practice of basic life support among junior doctors and students in a tertiary care medical institute

Background: Basic life support (BLS) is an integral part of health care. However, teaching of BLS is not yet a part of protocolized curriculum and uniform throughout. The present study is designed to assess the knowledge, attitude and practice of BLS and compare it among trained and untrained medical students and junior doctors in a medical institute.Methods: After approval from Institute Ethical Committee and informed consent from the participant, the present study was conducted among the undergraduate-level medical and nursing students and junior doctors. A questionnaire consisting of 30 questions based on knowledge, attitude and practice of BLS was used to collect data which is evaluated as per scale defined for this study. Statistical significance was assessed using INSTAT software (GraphPad Software, Inc., La Zolla, USA).Results: Only 16.41% of all participants and 52% of doctors have received class and/or hands on training. The untrained participants have scored poorly as compared to trained participants in theoretical knowledge and practice of BLS (24.36 % and 53.45% versus 9.25 % and 24.07%) respectively. The mean score for both theoretical knowledge and practice of BLS for trained students was higher than that of the untrained participants and the statistical difference was highly significant - p<0.0001. Most of the participants of both trained and untrained group were having very good attitude towards BLS.Conclusions: Knowledge and practice skills of BLS/CPR are poor in medical and nursing students. A significant portion of trainees do not acquire adequate knowledge in a single session of training. An organised curriculum for BLS and its protocolized training is the need of the hour in medical education.

Rotation-Agnostic Image Representation Learning for Digital Pathology

This paper addresses complex challenges in histopathological image analysis through three key contributions. Firstly, it introduces a fast patch selection method, FPS, for whole-slide image (WSI) analysis, significantly reducing computational cost while maintaining accuracy. Secondly, it presents PathDino, a lightweight histopathology feature extractor with a minimal configuration of five Transformer blocks and only 9 million parameters, markedly fewer than alternatives. Thirdly, it introduces a rotation-agnostic representation learning paradigm using self-supervised learning, effectively mitigating overfitting. We also show that our compact model outperforms existing state-of-the-art histopathology-specific vision transformers on 12 diverse datasets, including both internal datasets spanning four sites (breast, liver, skin, and colorectal) and seven public datasets (PANDA, CAMELYON16, BRACS, DigestPath, Kather, PanNuke, and WSSS4LUAD). Notably, even with a training dataset of 6 million histopathology patches from The Cancer Genome Atlas (TCGA), our approach demonstrates an average 8.5% improvement in patch-level majority vote performance. These contributions provide a robust framework for enhancing image analysis in digital pathology, rigorously validated through extensive evaluation. Project Page: https://rhazeslab.github.io/PathDino-Page/Comment: 23 pages, 10 figures, 18 tables. Histopathological Image Analysi

Learning Progression of Students’ Reasoning about Life Cycles

This study explored elementary students’ reasoning about the life cycles of various organisms, including insects and amphibians. The study took place in a private school in Lebanon with 24 fifth-grade students. Students participated in a life cycle unit with pre and post-written assessments about what they learned and interviews to help determine their reasoning about life cycles. Using our findings, we suggest a learning progression (LP) approach to guide students over time in their learning about life cycles and their importance for species persistence within an ecosystem. Two LPs were developed from this study: Reasoning about the cyclic nature of life and comparison of life cycle stages. Overall, students improved their understanding of the cyclical nature of life, but comparing organisms’ structures, stages, and life cycles proved to be more challenging. These LPs have direct implications for elementary instruction about life cycles, organisms, and species

Experimental investigation of waste tyres pyrolysis gas desulfurization through absorption in alkanolamines solutions

Copyright © 2022 The Authors. Pyrolysis of waste tyres produces harmful hydrogen sulfide and other mercaptan compounds as by-products. The current study is concerned with the purification of hydrogen-rich pyrolysis gas from hydrogen sulfide gas that is present in a great amount (up to 5.1% mol at 420 °C), and mercaptans that are also problematic impurities. The method proposed is absorption by alkanolamines which is one of the most economical methods applied in natural gas sweetening. However, it has not been adopted in waste tyre pyrolysis gas purification yet. Two organic absorbents were tested, diethanolamine (DEA), N-methyldiethanolamine (MDEA) as well as theirs blends, at various concentrations. The application of 30 wt% DEA in water reduced H2S emission by 98%. In turn, 40 wt% MDEA aqueous solutions reduced H2S emission by 97%. The best results were produced when 30 wt% DEA was mixed with 40 wt% of MDEA (1:1 vol ratio) which allowed a removal of 99% of H2S from the pyrolysis gas. Moreover, the maximum H2S emission was 7 ppm, and a level below 5 ppm was kept for 99% of experiments duration. Finally, the application of this mixture also reduced significantly the concentrations of other sulfur-containing compounds such as methyl mercaptan and carbonyl sulfide (a minimum of 98%), ethyl mercaptan (∼90%), and carbon disulphide (by more than 99%). Thus, aqueous solvent mixture of 30 wt% DEA with 40 wt% of MDEA (1:1 v/v) can be recommended as a potential desulfurization method for waste tyres pyrolysis gas.Department of Air Conditioning, Heating, Gas Engineering and Air Protection; Wroclaw University of Science and Technology (No. 8211204601 - N_RRB_PODST_BAD_ EXP_BAM)

Scalable and cost-effective NGS genotyping in the cloud

Background: While next-generation sequencing (NGS) costs have plummeted in recent years, cost and complexity of computation remain substantial barriers to the use of NGS in routine clinical care. The clinical potential of NGS will not be realized until robust and routine whole genome sequencing data can be accurately rendered to medically actionable reports within a time window of hours and at scales of economy in the 10’s of dollars. Results: We take a step towards addressing this challenge, by using COSMOS, a cloud-enabled workflow management system, to develop GenomeKey, an NGS whole genome analysis workflow. COSMOS implements complex workflows making optimal use of high-performance compute clusters. Here we show that the Amazon Web Service (AWS) implementation of GenomeKey via COSMOS provides a fast, scalable, and cost-effective analysis of both public benchmarking and large-scale heterogeneous clinical NGS datasets. Conclusions: Our systematic benchmarking reveals important new insights and considerations to produce clinical turn-around of whole genome analysis optimization and workflow management including strategic batching of individual genomes and efficient cluster resource configuration.Yassine Souilmi, Alex K. Lancaster, Jae-Yoon Jung, Ettore Rizzo, Jared B. Hawkins, Ryan Powles, Saaïd Amzazi, Hassan Ghazal, Peter J. Tonellato and Dennis P. Wal

Human cytomegalovirus IE86 protein interacts with promoter-bound TATA-binding protein via a specific region distinct from the autorepression domain

The major immediate-early gene of human cytomegalovirus encodes several isoforms of an immediate-early protein which has distinct transcriptional regulatory properties. The IE86 isoform autorepresses the major immediate-early promoter by directly binding the cis repression signal element located between the TATA box and the mRNA cap site. In addition to this activity, IE86 stimulates other viral and cellular promoters. One mechanism by which eukaryotic regulatory proteins are thought to stimulate transcription is by contacting one or more general transcription factors. We show that the IE86 protein physically interacts with the DNA-binding subunit (TATA-binding protein) human transcription factor IID via the TATA-binding protein-contacting domain in the N terminus of IE86. In a mobility shift assay, IE86 was also observed to stabilize the binding of TATA-binding protein to promoter DNA. The domains within IE86 responsible for mediating transactivation and repression functioned independently. These experiments thus demonstrate the elegant ability of human cytomegalovirus to join different protein domains to produce distinct multifunctional proteins

Ligand induction of retinoic acid receptors alters an acute infection by murine cytomegalovirus

Here we report that administration of retinoids can alter the outcome of an acute murine cytomegalovirus (MCMV) infection. We show that a crucial viral control element, the major immediate-early enhancer, can be activated by retinoic acid (RA) via multiple RA-responsive elements (DR2) that bind retinoid X receptor-retinoic acid receptor (RAR) heterodimers with apparent dissociation constants ranging from 15 to 33 nM. Viral growth is dramatically increased upon RA treatment of infected tissue culture cells. Using synthetic retinoid receptor-specific agonists and antagonists, we provide evidence that RAR activation in cells is required for mediating the response of MCMV to RA. Oral administration of RA to infected immunocompetent mice selectively exacerbates an infection by MCMV, while cotreatment with an RAR antagonist protects against the adverse effects of RA on MCMV infection. In conclusion, these chemical genetic experiments provide evidence that an RAR-mediated pathway can modulate in vitro and in vivo infections by MCMV