The Role of AI in Drug Discovery: Challenges, Opportunities, and Strategies

Artificial intelligence (AI) has the potential to revolutionize the drug discovery process, offering improved efficiency, accuracy, and speed. However, the successful application of AI is dependent on the availability of high-quality data, the addressing of ethical concerns, and the recognition of the limitations of AI-based approaches. In this article, the benefits, challenges and drawbacks of AI in this field are reviewed, and possible strategies and approaches for overcoming the present obstacles are proposed. The use of data augmentation, explainable AI, and the integration of AI with traditional experimental methods, as well as the potential advantages of AI in pharmaceutical research are also discussed. Overall, this review highlights the potential of AI in drug discovery and provides insights into the challenges and opportunities for realizing its potential in this field. Note from the human-authors: This article was created to test the ability of ChatGPT, a chatbot based on the GPT-3.5 language model, to assist human authors in writing review articles. The text generated by the AI following our instructions (see Supporting Information) was used as a starting point, and its ability to automatically generate content was evaluated. After conducting a thorough review, human authors practically rewrote the manuscript, striving to maintain a balance between the original proposal and scientific criteria. The advantages and limitations of using AI for this purpose are discussed in the last section.Comment: 11 pages, 1 figur

The HEARTS partner forum—supporting implementation of HEARTS to treat and control hypertension

Cardiovascular diseases (CVD), principally ischemic heart disease (IHD) and stroke, are the leading causes of death (18. 6 million deaths annually) and disability (393 million disability-adjusted life-years lost annually), worldwide. High blood pressure is the most important preventable risk factor for CVD and deaths, worldwide (10.8 million deaths annually). In 2016, the World Health Organization (WHO) and the United States Centers for Disease Control (CDC) launched the Global Hearts initiative to support governments in their quest to prevent and control CVD. HEARTS is the core technical package of the initiative and takes a public health approach to treating hypertension and other CVD risk factors at the primary health care level. The HEARTS Partner Forum, led by WHO, brings together the following 11 partner organizations: American Heart Association (AHA), Center for Chronic Disease Control (CCDC), International Society of Hypertension (ISH), International Society of Nephrology (ISN), Pan American Health Organization (PAHO), Resolve to Save Lives (RTSL), US CDC, World Hypertension League (WHL), World Heart Federation (WHF) and World Stroke Organization (WSO). The partners support countries in their implementation of the HEARTS technical package in various ways, including providing technical expertise, catalytic funding, capacity building and evidence generation and dissemination. HEARTS has demonstrated the feasibility and acceptability of a public health approach, with more than seven million people already on treatment for hypertension using a simple, algorithmic HEARTS approach. Additionally, HEARTS has demonstrated the feasibility of using hypertension as a pathfinder to universal health coverage and should be a key intervention of all basic benefit packages. The partner forum continues to find ways to expand support and reinvigorate enthusiasm and attention on preventing CVD. Proposed future HEARTS Partner Forum activities are related to more concrete information sharing between partners and among countries, expanded areas of partner synergy, support for implementation, capacity building, and advocacy with country ministries of health, professional societies, academy and civil societies organizations. Advancing toward the shared goals of the HEARTS partners will require a more formal, structured approach to the forum and include goals, targets and published reports. In this way, the HEARTS Partner Forum will mirror successful global partnerships on communicable diseases and assist countries in reducing CVD mortality and achieving global sustainable development goals (SDGs)

The Heart of the World

Cardiovascular diseases (CVDs) are the leading cause of mortality globally. Of the 20.5 million CVD-related deaths in 2021, approximately 80% occurred in low- and middle-income countries. Using data from the Global Burden of Disease Study, NCD Risk Factor Collaboration, NCD Countdown initiative, WHO Global Health Observatory, and WHO Global Health Expenditure database, we present the burden of CVDs, associated risk factors, their association with national health expenditures, and an index of critical policy implementation. The Central Europe, Eastern Europe, and Central Asia region face the highest levels of CVD mortality globally. Although CVD mortality levels are generally lower in women than men, this is not true in almost 30% of countries in the North Africa and Middle East and Sub-Saharan regions. Raised blood pressure remains the leading global CVD risk factor, contributing to 10.8 million deaths in 2019. The regions with the highest proportion of countries achieving the maximum score for the WHF Policy Index were South Asia, Central Europe, Eastern Europe, and Central Asia, and the High-Income regions. The Sub-Saharan Africa region had the highest proportion of countries scoring two or less. Policymakers must assess their country’s risk factor profile to craft effective strategies for CVD prevention and management. Fundamental strategies such as the implementation of National Tobacco Control Programmes, ensuring the availability of CVD medications, and establishing specialised units within health ministries to tackle non-communicable diseases should be embraced in all countries. Adequate healthcare system funding is equally vital, ensuring reasonable access to care for all communities

Interactions Between Laminin Receptor and the Cytoskeleton During Translation and Cell Motility

Human laminin receptor acts as both a component of the 40S ribosomal subunit to mediate cellular translation and as a cell surface receptor that interacts with components of the extracellular matrix. Due to its role as the cell surface receptor for several viruses and its overexpression in several types of cancer, laminin receptor is a pathologically significant protein. Previous studies have determined that ribosomes are associated with components of the cytoskeleton, however the specific ribosomal component(s) responsible has not been determined. Our studies show that laminin receptor binds directly to tubulin. Through the use of siRNA and cytoskeletal inhibitors we demonstrate that laminin receptor acts as a tethering protein, holding the ribosome to tubulin, which is integral to cellular translation. Our studies also show that laminin receptor is capable of binding directly to actin. Through the use of siRNA and cytoskeletal inhibitors we have shown that this laminin receptor-actin interaction is critical for cell migration. These data indicate that interactions between laminin receptor and the cytoskeleton are vital in mediating two processes that are intimately linked to cancer, cellular translation and migration

Management of Cardiovascular Disease Patients With Confirmed or Suspected COVID-19 in Limited Resource Settings

In this paper, we provide recommendations on the management of cardiovascular disease (CVD) among patients with confirmed or suspected coronavirus disease (COVID-19) to facilitate the decision making of healthcare professionals in low resource settings. The emergence of novel coronavirus disease, also known as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has presented an unprecedented global challenge for the healthcare community. The ability of SARS-CoV-2 to get transmitted during the asymptomatic phase and its high infectivity have led to the rapid transmission of COVID-19 beyond geographic regions, leading to a pandemic. There is concern that COVID-19 is cardiotropic, and it interacts with the cardiovascular system on multiple levels. Individuals with established CVD are more susceptible to severe COVID-19. Through a consensus approach involving an international group this WHF statement summarizes the links between cardiovascular disease and COVID-19 and present some practical recommendations for the management of hypertension and diabetes, acute coronary syndrome, heart failure, rheumatic heart disease, Chagas disease, and myocardial injury for patients with COVID-19 in low-resource settings. This document is not a clinical guideline and it is not intended to replace national clinical guidelines or recommendations. Given the rapidly growing burden posed by COVID-19 illness and the associated severe prognostic implication of CVD involvement, further research is required to understand the potential mechanisms linking COVID-19 and CVD, clinical presentation, and outcomes of various cardiovascular manifestations in COVID-19 patients

Características clínico-epidemiológicas de pacientes hipertensos en un Consultorio Médico de Santa Clara

High blood pressure is a chronic non-transmittable disease, which is also a risk factor for the development of other clinical conditions. The incidence of arterial hypertension in the Cuban population is high.Aim: to characterize the evolution of arterial hypertension in a Family Doctor's Office.Methods: an observational, descriptive and cross-sectional study was carried out at the Family Doctor's Office 17-19 in the municipality of Santa Clara. The study covered the months of January to March 2020. Of the 256 hypertensive patients, a sample of 52 was selected by a simple random method.Results: Males predominated (53.84 %), together with the age group between 40 and 49 years (28.84 %). A total of 63.46 % of the patients were white-skinned. 51.61% presented risk factors. The risk factors with the highest incidence were smoking, followed by obesity and sedentary lifestyle.Conclusions: the most affected hypertensive patients are male. Most patients have a family history of high blood pressure. Smoking is a high incidence risk factor in the hypertensive population.Introducción: la hipertensión arterial es una enfermedad crónica no transmisible, que a la vez constituye un factor de riesgo para el desarrollo de otras enfermedades. La incidencia de la hipertensión arterial en la población de Cuba es alta.Objetivo: caracterizar el comportamiento de la hipertensión arterial en un Consultorio Médico de Familia.Métodos: se realizó un estudio observacional, descriptivo y transversal en el Consultorio Médico de Familia 17-19 del municipio Santa Clara. El período de estudio comprendió los meses de enero a marzo del 2020. La población fue de 256 hipertensos y se escogió una muestra de 52 hipertensos por muestreo aleatorio simple.Resultados: predominó el sexo masculino (53,84 %), y el grupo de edad entre 40 y 49 años (28,84 %). El 63,46 % de los pacientes fueron de color de la piel blanca. El 51,61 % presentaron factores de riesgo. Los factores de riesgo de mayor incidencia fueron el tabaquismo, seguido por la obesidad y el sedentarismo.Conclusiones: los pacientes hipertensos más afectados son los del sexo masculino. La mayor parte de los pacientes tienen antecedentes familiares de hipertensión arterial. El tabaquismo es un factor de riesgo de alta incidencia en la población hipertensa

ACAULIS5, an Arabidopsis gene required for stem elongation, encodes a spermine synthase

Polyamines have been implicated in a wide range of biological processes, including growth and development in bacteria and animals, but their function in higher plants is unclear. Here we show that the Arabidopsis ACAULIS5 (ACL5) gene, whose inactivation causes a defect in the elongation of stem internodes by reducing cell expansion, encodes a protein that shares sequence similarity with the polyamine biosynthetic enzymes spermidine synthase and spermine synthase. Expression of the recombinant ACL5 protein in Escherichia coli showed that ACL5 possesses spermine synthase activity. Restoration of the acl5 mutant phenotype by somatic reversion of a transposon-induced allele suggests a non-cell-autonomous function for the ACL5 gene product. We also found that expression of the ACL5 cDNA under the control of a heat shock gene promoter in acl5 mutant plants restores the phenotype in a heat shock-dependent manner. The results of the experiments showed that polyamines play an essential role in promotion of internode elongation through cell expansion in Arabidopsis. We discuss the relationships to plant growth regulators such as auxin and gibberellins that have related functions

Ecological and social basis for the development of a sand barrier breaching model in Laguna de Rocha, Uruguay

Special thanks to Hugo Inda for technical support, and to Carolina Cabrera and Lucía Nogueira for helping with the references. We also thank two anonymous reviewers for valuable comments and suggestions. This study was made possible through the partial financial support from DINAMA-UCC/SNAP (MVOTMA/Uruguay), Fundación de Amigos de las Lagunas Costeras de Rocha (Uruguay), Interamerican Institute for Global Change (IAI-CRN; 3038/SAFER Project), and International Development Research Centre (IDRC-Climate Change & Water Program; Grant 6923001).Sand barrier complex dynamics play a key role in defining coastal lagoon structure and functioning. Artificial manipulation of these dynamics for biased reasons (e.g., controlling floods, improving fisheries) aggravates conflicts between stakeholders and introduces potential threats to their conservation. This is the case at Laguna de Rocha, Uruguay, a protected area with international recognition, where the sand barrier opening has been the focus of a long-term conflict. A cooperative effort of scientists, authorities, and local stakeholders produced a breaching protocol, aimed to reduce conflicts while preserving the natural hydrodynamics of the system and its associated ecological processes. Historical information and present perceptions about the sand barrier breach were collected, and geomorphological and hydrological studies were carried out. Reconstruction of the historical management of the breaching practice showed that the artificial opening started in the 1950s and that the original procedure, performed by fishermen and cattle ranchers, was gradually left under to managers to, and it is presently performed with heavy machinery. Since the 1980s, inappropriate opening practices may have produced negative effects on the physical and biological structure of the lagoon. Geomorphological studies revealed the sand barrier as a highly vulnerable component of the lagoon and suggested that new opening sites could eventually develop over the long term, given the predictions of climate change and sea level rise. The hydrological approach provided an understanding of the processes driving the opening mechanism and the extent of the flooding of private and public lands. These results outlined the basis for the protocol, to support managers in deciding when to perform the opening, based on a reduced set of indicators (water depth, sand barrier berm elevation, and rainfall forecasts). Reaching a consensus was mainly based upon the existence, for more than 15 years, of a participatory advisory group discussing local environmental problems. The new sand barrier breaching protocol is a significant improvement over the previous situation, and can be generalized for application in similar contexts