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Artemisinin resistance constitutes a major threat to the continued success of control programs for malaria. With alternative antimalarial drugs not yet available, improving our understanding of how artemisinin-based drugs act and how resistance manifests is essential to enable optimisation of dosing regimens in order to prolong the lifespan of current first-line treatment options. Here, through introduction of a novel model of the dynamics of the

ABSTRACT Recent advances in curbing the deadly toll of malaria have been threatened by the emergence of parasites resistant to the front-line antimalarial artemisinin. Resistance is mediated by point-mutations in the parasite protein Kelch13, but the mechanism of resistance is multi-factorial and only partially understood. Resistance-conferring Kelch13 mutations have been shown to lead to low-level activation of the parasite’s int

Artemisinin-based combination therapies are the first line of treatment for Plasmodium falciparum infections worldwide, but artemisinin resistance has risen rapidly in Southeast Asia over the past decade. Mutations in the kelch13 gene have been implicated in this resistance. We used longitudinal genomic surveillance to detect signals in kelch13 and other loci that contribute to artemisinin or partner drug resistance. We retrospectively sequenced

Malaria, caused by Plasmodium parasites and transmitted by Anopheles mosquitoes, greatly impacts public health and socioeconomic development, particularly in sub-Saharan African countries. Despite advances in malaria treatment and prevention, the number of clinical cases and deaths have increased in recent years. The complex life cycle and genetic diversity of Plasmodium parasites pose significant challenges in drug and vaccine development, parti

Faculty Opinions recommendation of Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. was ingested from crossref.

Mounting evidence demonstrates that nutritional environment can alter pathogen drug sensitivity. While the rich media used for in vitro culture contains supraphysiological nutrient concentrations, pathogens encounter a relatively restrictive environment in vivo . We assessed the effect of nutrient limitation on the protozoan parasite that causes malaria and demonstrated that short-term growth under physiologically relevant mild nutrient stress (o

Quantitative structure-activity relationship (QSAR) modelling, an approach that was introduced 60 years ago, is widely used in computer-aided drug design. In recent years, progress in artificial intelligence techniques, such as deep learning, the rapid growth of databases of molecules for virtual screening and dramatic improvements in computational power have supported the emergence of a new field of QSAR applications that we term 'deep QSAR'. Ma

Recent advances in large language models (LLMs) have shown great potential to accelerate drug discovery. However, the specialized nature of biochemical data often necessitates costly domain-specific fine-tuning, posing major challenges. First, it hinders the application of more flexible general-purpose LLMs for cutting-edge drug discovery tasks. More importantly, it limits the rapid integration of the vast amounts of scientific data continuously

The recent development of quantum computing, which uses entanglement, superposition, and other quantum fundamental concepts, can provide substantial processing advantages over traditional computing. These quantum features help solve many complex problems that cannot be solved otherwise with conventional computing methods. These problems include modeling quantum mechanics, logistics, chemical-based advances, drug design, statistical science, susta

Artificial intelligence (AI) consists of a synergistic assembly of enhanced optimization strategies with wide application in drug discovery and development, providing advanced tools for promoting cost-effectiveness throughout drug life cycle. Specifically, AI brings together the potential to improve drug approval rates, reduce development costs, get medications to patients faster, and help patients complying with their treatments. Accelerated pha

Malaria remains a preventable and treatable disease; however, recent efforts to reduce mortality have plateaued. Although artemisinin-based combination therapy demonstrates high efficacy in controlled clinical settings, its real-world effectiveness is often compromised by suboptimal patient adherence. Specifically, the artemether-lumefantrine regimen, administered twice daily over 3 days, has been associated with reduced compliance due to its com

<h4>Background</h4>Malaria remains a major public health burden in Tanzania, where Plasmodium falciparum accounts for 96% of infections and children under five years experience the highest mortality. The emergence of kelch13 mutations and partial resistance to artemisinin derivatives poses a threat to the sustainability of artemisinin-based combination therapy (ACT). Reliance on artemether-lumefantrine (ALU) as the dominant first-line treatment i

Current first-line artemisinin antimalarials are threatened by the emergence of resistant Plasmodium falciparum. Decreased sensitivity is evident in the initial (early ring) stage of intraerythrocytic development, meaning that it is crucial to understand the action of artemisinins at this stage. Here, we examined the roles of iron (Fe) ions and haem in artemisinin activation in early rings using Fe ion chelators and a specific haemoglobinase inhi

Large-scale structural interventions and “Big Events” like revolutions, wars and major disasters can affect HIV transmission by changing the sizes of at-risk populations, making high-risk behaviors more or less likely, or changing contexts in which risk occurs. This paper describes new measures to investigate hypothesized pathways that could connect macro-social changes to subsequent HIV transmission. We developed a “menu” of novel scales and ind

Decision letter: Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness was ingested from crossref.

Molecular Determinants of Artemisinin Resistance in k13 Gene of Plasmodium falciparum was ingested from crossref.

Author response: Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance was ingested from crossref.

Decision letter: Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance was ingested from crossref.

<h4>Background</h4>Malaria continues to pose a major public health challenge in sub-Saharan Africa (SSA), where more than 95% of global cases and deaths occur. Despite WHO Global Technical Strategy for Malaria (GTS) targeting a 90% reduction in malaria mortality by 2030, progress is hindered by persistent transmission conditions, fragile health systems, and emerging resistance to drugs and insecticides. Epidemiological models are increasingly app

Quantum computing is poised to revolutionize biomedicine and healthcare, offering computational advantages that surpass classical and artificial intelligence-based approaches. Its ability to process complex biological data, simulate molecular interactions, and optimize drug discovery presents unprecedented opportunities for personalized medicine and disease modeling. Quantum algorithms can enhance genomic analysis, accelerating diagnostics and th

Maternal-newborn care does not always align with the best available evidence. Applying implementation science to change initiatives can help move evidence-informed practices into clinical settings. However, it remains unknown to what extent current implementation practices in maternal-newborn care align with recommendations from implementation science, and how confident nurses, other health professionals, and leaders are completing steps in the i

A pervasive view is that undifferentiated stem cells are alone responsible for generating all other cells and are the origins of cancer. However, emerging evidence demonstrates fully differentiated cells are plastic, can be coaxed to proliferate, and also play essential roles in tissue maintenance, regeneration, and tumorigenesis. Here, we review the mechanisms governing how differentiated cells become cancer cells. First, we examine the unique c

Falciparum malaria is a major parasitic disease causing widespread morbidity and mortality globally. Artemisinin derivatives---the most effective and widely-used antimalarials that have helped reduce the burden of malaria by 60% in some areas over the past decade---have recently been found to induce growth retardation of blood-stage Plasmodium falciparum when applied at clinically relevant concentrations. To date, no model has been designed to qu

CRISPR-Cas systems are an adaptive immunity that protects prokaryotes against foreign genetic elements. Genetic templates acquired during past infection events enable DNA-interacting enzymes to recognize foreign DNA for destruction. Due to the programmability and specificity of these genetic templates, CRISPR-Cas systems are potential alternative antibiotics that can be engineered to self-target antimicrobial resistance genes on the chromosome or

Artemisinin resistant kelch13 R622I and RDT negativity approaching predominance in northern Ethiopia and emerging C580Y of African origin threaten falciparum malaria control. was ingested from pubmed.

Abstract Background To engage with the public during World Antimicrobial Resistance Awareness Week (WAAW) 2024, several UK local, regional and national organizations, comprising Health Innovation East, Cambridgeshire & Peterborough ICS, Antibiotic Research UK (ANTRUK), and NHSE East of England (EOE), came together and launched an e-platform containing an interactive quiz. This project provided a digital, collaborative and cost-effective way of ha

Abstract: This article offers a comprehensive analysis of Artificial General Intelligence (AGI) development through a humanistic lens. Utilizing a wide array of academic and industry resources, it dissects the technological and ethical complexities inherent in AGI's evolution. Specifically, the paper underlines the societal and individual implications of AGI and argues for its alignment with human values and interests. Purpose: The study aims to

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably

Emerging infectious diseases have risen significantly in the twenty-first century as ecological disruption, climate change, expanding human-animal interfaces, and global mobility intensify opportunities for pathogen transmission. This review synthesizes historical and contemporary evidence across viral, bacterial, fungal, and parasitic threats to characterize how diverse pathogens emerge and spread. Foundational events such as the 1918 influenza

This final chapter looks back on what is meant by theory and theorising and suggests ways in which we can improve the way we theorise technology in education. It contains a proposal for a more distinctively educational research community focused on a critical exploration of digital tools and their contribution to education.

Increased usage of the internet has contributed immensely to the growth of software development practice in East Africa. This paper investigates the existence of formal KM (Knowledge Management) initiatives in the Software industry such as creation of virtual communities (Communities of practice and communities of interest); expert localization and establishment of knowledge taxonomies in these communities; the knowledge transfer and sharing proc

The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. was ingested from semantic-scholar.

Summary Background There is a scarcity of published data on the global prevalence of obstructive sleep apnoea, a disorder associated with major neurocognitive and cardiovascular sequelae. We used publicly available data and contacted key opinion leaders to estimate the global prevalence of obstructive sleep apnoea. Methods We searched PubMed and Embase to identify published studies reporting the prevalence of obstructive sleep apnoea based on obj

Migration is an important global issue as poorly managed migration can result in a diversity of problems, including an increase in the transmission of diseases such as malaria. There is evidence to suggest that malaria is no longer a forest-dependent disease and may largely be affected by population movements, mostly to agricultural areas. While internal and transnational migration has different legal implications in most countries, both types of

The exponential demand for energy-efficient and adaptive computing architectures drives the evolution of artificial intelligence (AI) and machine learning (ML). Neuromorphic computing, inspired by biological neural networks, overcomes the limitations of traditional von Neumann architectures, including high energy consumption and limited scalability. The introduction of two-dimensional (2D) materials, such as transition metal dichalcogenides, hexa

Artificial intelligence is typically formulated as an information-processing system composed of artificial neurons, where computation is understood as recursive operations connecting inputs and outputs. However, real neural systems are materially embodied and continuously reconfigured by metabolic and physical processes, suggesting that computation cannot be reduced to fixed causal structures. In this paper, we propose a theoretical framework tha

As a cheap and safe antimalarial agent, chloroquine (CQ) has been used in the battle against malaria for more than half century. However, the mechanism of CQ action and resistance in Plasmodium falciparum remains elusive. Based on further analysis of our published experimental results, we propose that the mechanism of CQ action and resistance might be closely linked with cell-cycle-associated amplified genomic-DNA fragments (CAGFs, singular form

Plasmodium falciparum is the parasite that causes the most severe form of malaria. Currently, science has been established about its cellular structures, its metabolic processes, and even the molecular structures of its intrinsic membrane proteins responsible for transporting water, nutrient, and waste molecules across the parasite plasma membrane (PPM). I hypothesize that Plasmodium falciparum has an Achilles' heel that can be attacked with eryt

From this point of the book forward, I ask you to think about the challenges described in chapter 1 from a civic educator’s perspec­tive. That is, consider the perspective of a person who wants to increase other people’s knowledge about politics or their competence at a politically relevant task. With that perspective in mind, I first convey a few important facts about civic educators and their aspirations. Next, I present a plan for helping many

<p>Artificial intelligence (AI) has become a major topic of public and scientific debate, whereas public perceptions of quantum computing (QC) remain less understood. In the present study, we aimed to understand if people have different views on AI vs. QC, while also asking them about their perceived knowledge levels in these two domains. Further, we investigated the construct of technology self-efficacy to consider how people in general think th

What AI Can Do for Neuroscience: Understanding How the Brain Represents Word Meanings was ingested from crossref.

Explanations, explanations, explanations: how do patients with limited English construct narrative accounts in multi-lingual, multi-ethnic settings, and how can GPs interpret them? was ingested from crossref.

Resistance to Change in an Organization was ingested from semantic-scholar.

Sleep and human cognitive development. was ingested from pubmed.

New Insights into CRISPR Arrays was ingested from crossref.

CRISPR/Cas has the potential to revolutionize medicine, agriculture, and biology. Understanding the trajectory of CRISPR research, how it is influenced and who pays for it, is an essential research policy question. We use a combination of methods to map, via quantitative content analysis of CRISPR papers, the research funding profile of major government agencies and organizations philanthropic, and the networks involved in supporting key stages o

China Shows What Economic Liberalism Can Do was ingested from crossref.

Polymorphisms of Plasmodium falciparum k13-propeller gene among migrant workers returning to Henan Province, China from Africa. was ingested from pubmed.

This paper applies statistical learning techniques to an observational Quantified-Self (QS) study to build a descriptive model of sleep quality. A total of 472 days of my sleep data was collected with an Oura ring and combined with lifestyle, environmental, and psychological data. Such n-of-1 QS projects pose a number of challenges: heterogeneous data sources; missing values; high dimensionality; dynamic feedback loops; human biases. This paper d

De novo enzyme design seeks to build proteins containing ideal active sites with catalytic residues surrounding and stabilizing the transition state(s)&#xa0;of the target chemical reaction 1-7 . The generative artificial intelligence method RFdiffusion 8,9 solves this problem, but requires specifying both the sequence position and backbone coordinates for each catalytic residue, limiting sampling. Here we introduce RFdiffusion2, which eliminates

If the euro is to seriously rival the dollar as an international currency, the size of the eurozone’s capital markets must match those of the United States. The eurozone’s bond markets present a particularly acute problem in this context because far from closing the size gap with the US bond markets, that gap continues to widen considerably. This chapter will argue that to reverse this situation, two things above all else are required. First, tha

I-mode is a promising regime for future fusion reactors due to the high energy confinement and the moderate particle confinement. However, the effect of lithium, which has been widely applied for particle recycling and impurity control, on I-mode plasma is still unclear. Recently, experiments of real-time lithium powder injection on I-mode plasma have been carried out in EAST Tokamak. It was found that the confinement performance of the I-mode ca

Study Objective: Sleep is reflected not only in the electroencephalogram but also in heart rhythms and breathing patterns. Therefore, we hypothesize that it is possible to accurately stage sleep based on the electrocardiogram (ECG) and respiratory signals. Methods: Using a dataset including 8,682 polysomnographs, we develop deep neural networks to stage sleep from ECG and respiratory signals. Five deep neural networks consisting of convolutional