Combating trade in illegal wood and forest products with machine learning.

Trade in wood and forest products spans the global supply chain. Illegal logging and associated trade in forest products present a persistent threat to vulnerable ecosystems and communities. Illegal timber trade has been linked to violations of tax and conservation laws, as well as broader transnational crimes.

PET Imaging of a Transgenic Tau Rat Model SHR24 with [F]AV1451.

Purpose: Positron Emission Tomography (PET) scans with radioligands targeting tau neurofibrillary tangles (NFT) have accelerated our understanding of the role of misfolded tau in neurodegeneration. While intended for human research, applying these radioligands to small animals establishes a vital translational link. Transgenic animal models of dementia, such as the tau rat SHR24, play a crucial role in enhancing our understanding of these disorders.

A probabilistic approach to estimating timber harvest location.

Determining the harvest location of timber is crucial to enforcing international regulations designed to protect natural resources and to tackle illegal logging and associated trade in forest products. Stable isotope ratio analysis (SIRA) can be used to verify claims of timber harvest location by matching levels of naturally occurring stable isotopes within wood tissue to location-specific ratios predicted from reference data ("isoscapes"). However, overly simple models for predicting isoscapes have so far limited the confidence in derived predictions of timber provenance.

Improvements in large-scale production of tobacco etch virus protease.

Tobacco-etch-virus (TEV) protease is the workhorse of many laboratories in which protein expression is the linchpin of downstream experiments. TEV protease is remarkable in its sequence specificity as the cleavage sequence rarely appears in higher organisms and its ability to cleave fusion tag proteins from proteins of interest. Herein we report work done on large-scale production of TEV protease using different promotors, media, fusion tags, and expression platforms.

Electrophoresis and Quartz Crystal Microbalance Instrumentation to Sense Nanoplastics in Water.

We report a Technical Note on detecting nanoplastics in water samples through electrophoresis and quartz crystal microbalance (QCM) instrumentation. We conducted electrophoresis experiments by immersing a QCM in a sample of ultrapure water containing polyethylene (PE) nanoplastics. It was interesting to observe that nanoplastics were attracted toward the QCM and adhered to one side of the QCM electrode.

A Preliminary Investigation of a Conceptual Model Describing the Associations Between Childhood Maltreatment and Alcohol Use Problems.

Background/objectives: Childhood maltreatment has been linked to numerous adverse outcomes in adulthood, including problem substance use. However, not all individuals exposed to childhood maltreatment develop substance use problems, indicating the role of other factors in influencing this outcome. Past work suggests that adverse early life experiences, including childhood maltreatment, lead to neurobiological changes in frontolimbic functions that, in turn, result in altered stress and reward responses, heightened impulsivity, affect dysregulation, and, ultimately, increased risk for maladaptive behaviors such as substance use.

Post-ICU Care: Why, What, When and How? ISCCM Position Statement.

Ramakrishnan N, Abraham BK, Barokar R, Chanchalani G, Jagathkar G, Shetty RM, . Post-ICU Care: Why, What, When and How? ISCCM Position Statement. Indian J Crit Care Med 2024;28(S2):S279-S287.

Learning cardiac embryology on YouTube-What videos are there to view?

In modern medical curricula, embryology is typically taught through lectures, with a few institutions providing tutorials. The use of 3-D videos or animations enables students to study these embryological structures and how they change with time. The aim of this study was to assess the quality of cardiac embryology videos available on YouTube.

Nucleolytic processing of abasic sites underlies PARP inhibitor hypersensitivity in ALC1-deficient BRCA mutant cancer cells.

Clinical success with poly (ADP-ribose) polymerase inhibitors (PARPi) is impeded by inevitable resistance and associated cytotoxicity. Depletion of Amplified in Liver Cancer 1 (ALC1), a chromatin-remodeling enzyme, can overcome these limitations by hypersensitizing BReast CAncer genes 1/2 (BRCA1/2) mutant cells to PARPi. Here, we demonstrate that PARPi hypersensitivity upon ALC1 loss is reliant on its role in promoting the repair of chromatin buried abasic sites.

Determining KRAS4B-Targeting Compound Specificity by Top-Down Mass Spectrometry.

We present a novel method to determine engagement and specificity of KRAS4B-targeting compounds in vitro. By employing top-down mass spectrometry (MS), which analyzes intact and modified protein molecules (proteoforms), we can directly visualize and confidently characterize each KRAS4B species within compound-treated samples. Moreover, by employing targeted MS2 fragmentation, we can precisely localize each compound molecule to a specific residue on a given KRAS4B proteoform.

Producing recombinant proteins in Vibrio natriegens.

The diversity of chemical and structural attributes of proteins makes it inherently difficult to produce a wide range of proteins in a single recombinant protein production system. The nature of the target proteins themselves, along with cost, ease of use, and speed, are typically cited as major factors to consider in production. Despite a wide variety of alternative expression systems, most recombinant proteins for research and therapeutics are produced in a limited number of systems: Escherichia coli, yeast, insect cells, and the mammalian cell lines HEK293 and CHO.

Free energy calculations for membrane morphological transformations and insights to physical biology and oncology.

In this chapter, we aim to bridge basic molecular and cellular principles surrounding membrane curvature generation with rewiring of cellular signals in cancer through multiscale models. We describe a general framework that integrates signaling with other cellular functions like trafficking, cell-cell and cell-matrix adhesion, and motility. The guiding question in our approach is: how does a physical change in cell membrane configuration caused by external stimuli (including those by the extracellular microenvironment) alter trafficking, signaling and subsequent cell fate? We answer this question by constructing a modeling framework based on stochastic spatial continuum models of cell membrane deformations.

Asymmetric crowders and membrane morphology at the nexus of intracellular trafficking and oncology.

A definitive understanding of the interplay between protein binding/migration and membrane curvature evolution is emerging but needs further study. The mechanisms defining such phenomena are critical to intracellular transport and trafficking of proteins. Among trafficking modalities, exosomes have drawn attention in cancer research as these nano-sized naturally occurring vehicles are implicated in intercellular communication in the tumor microenvironment, suppressing anti-tumor immunity and preparing the metastatic niche for progression.

Differentiating ischemic stroke patients from healthy subjects using a large-scale, retrospective EEG database and machine learning methods.

Objectives: We set out to develop a machine learning model capable of distinguishing patients presenting with ischemic stroke from a healthy cohort of subjects. The model relies on a 3-min resting electroencephalogram (EEG) recording from which features can be computed.

Materials And Methods: Using a large-scale, retrospective database of EEG recordings and matching clinical reports, we were able to construct a dataset of 1385 healthy subjects and 374 stroke patients.

Improving Antimicrobial Resistance Awareness Among Medical Students in India: The Sensitization of Medical Students on Antimicrobial Resistance (SOS-AMR) Study.

Objectives: To evaluate the impact of an online educational intervention on improving knowledge of antimicrobial resistance (AMR) and stewardship among final-year medical students in Chennai, India.

Methods: This was a prospective 'before-after' study conducted across 5 medical colleges in Chennai, India. Participants who were final-year (fourth year) undergraduate medical students were administered a pretest to evaluate baseline knowledge.

Teleradiology: Geography is now History!

Ramakrishnan N. Teleradiology: Geography is now History! Indian J Crit Care Med 2024;28(1):1-2.

A Top-Down Proteomic Assay to Evaluate KRAS4B-Compound Engagement.

Development of new targeted inhibitors for oncogenic KRAS mutants may benefit from insight into how a given mutation influences the accessibility of protein residues and how compounds interact with mutant or wild-type KRAS proteins. Targeted proteomic analysis, a key validation step in the KRAS inhibitor development process, typically involves both intact mass- and peptide-based methods to confirm compound localization or quantify binding. However, these methods may not always provide a clear picture of the compound binding affinity for KRAS, how specific the compound is to the target KRAS residue, and how experimental conditions may impact these factors.

Author Response.

Tirupakuzhi Vijayaraghavan BK, Venkataraman R, Ramakrishnan N. Author Response. Indian J Crit Care Med 2024;28(3):312.

A high-content flow cytometry and dual CRISPR-Cas9 based platform to quantify genetic interactions.

Probing epistasis between two genes can be a critical first step in identifying the molecular players in a cellular pathway. The advent of CRISPR-Cas mediated genetic screen has enabled studying of these genetic interactions at a genomic scale. However, when combining depletion of two genes using CRISPR Cas9, reduced targeting efficiencies due to competition for Cas loading and recombination in the cloning step have emerged as key challenges.

Comparative analysis of KRAS4a and KRAS4b splice variants reveals distinctive structural and functional properties.

, the most frequently mutated oncogene in human cancer, produces two isoforms, KRAS4a and KRAS4b, through alternative splicing. These isoforms differ in exon 4, which encodes the final 15 residues of the G-domain and hypervariable regions (HVRs), vital for trafficking and membrane localization. While KRAS4b has been extensively studied, KRAS4a has been largely overlooked.

Evaluation of FluSight influenza forecasting in the 2021-22 and 2022-23 seasons with a new target laboratory-confirmed influenza hospitalizations.

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. Forecasting teams were asked to provide national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one through four weeks ahead for the 2021-22 and 2022-23 influenza seasons. Across both seasons, 26 teams submitted forecasts, with the submitting teams varying between seasons.

A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial.

Background: The burden of sepsis is high in India and is associated with substantial morbidity and mortality. Vitamin C, an endogenous antioxidant, may improve patient outcomes.

Methods: This was a parallel-group pilot feasibility randomized controlled trial conducted at 2 intensive care units in India.

Approach to Intensive Care Costing and Provision of Cost-effective Care.

Unlabelled: Intensive care unit (ICU) service is resource-intense, finite, and valuable. The outcome of critically ill patients has improved because of a better understanding of disease pathology, technological developments, and newer treatment modalities. These improvements have however come at a price, with ICUs contributing significantly to health budgets.