Transformers and Large Language Models for Chemistry and Drug Discovery

Language modeling has seen impressive progress over the last years, mainly prompted by the invention of the Transformer architecture, sparking a revolution in many fields of machine learning, with breakthroughs in chemistry and biology. In this chapter, we explore how analogies between chemical and natural language have inspired the use of Transformers to tackle important bottlenecks in the drug discovery process, such as retrosynthetic planning and chemical space exploration. The revolution started with models able to perform particular tasks with a single type of data, like linearised molecular graphs, which then evolved to include other types of data, like spectra from analytical instruments, synthesis actions, and human language. A new trend leverages recent developments in large language models, giving rise to a wave of models capable of solving generic tasks in chemistry, all facilitated by the flexibility of natural language. As we continue to explore and harness these capabilities, we can look forward to a future where machine learning plays an even more integral role in accelerating scientific discovery

Taller de monitoreo participativo. Evolución de indicadores con impacto en la sustentabilidad (2016-2019). Informe final

En el territorio de influencia de la Agencia de Extensión Rural (AER) del INTA de Ingeniero Jacobacci, Provincia de Río Negro, se encuentra un Sitio Piloto del Observatorio Nacional de Degradación de Tierras y Desertificación (ONDTyD1). El sitio fue elegido por ser representativo de una extensa región patagónica, y contar con estudios y acciones desarrollados por el INTA en cooperación con otras agencias de I+D, como el Proyecto LADA2 y anteriormente el Proyecto PRODESAR3. En base a estos antecedentes se consideró que el desarrollo de un Observatorio sería un dispositivo novedoso para el abordaje de la complejidad que representa la desertificación y el estancamiento crónico en el desarrollo rural de la región4. El mismo se planteó con el objetivo de generar información sobre la evolución rural regional en las dimensiones natural, social y económico-productiva, propiciando espacios de articulación y participación, tanto para la obtención de información, como para la reflexión sobre la información obtenida. Luego de un primer periodo de relevar información de base tanto biofísica como socio-económica5, en el ONDTyD se planteó la realización de Talleres Participativos en la red de Sitios Piloto que lo integran, que permitan evaluar los cambios ocurridos en el período comprendido entre los años 2015/2016 y 2019-2020.Estación Experimental Agropecuaria BarilocheFil: Bran, Donaldo Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; ArgentinaFil: Velasco, Virginia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Agencia de Extensión Rural Ing. Jacobacci; ArgentinaFil: Fantozzi, Anabella. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; ArgentinaFil: Gaetano, Andrés Marcelo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Agencia de Extensión Rural Ing. Jacobacci; Argentin

14 Examples of How LLMs Can Transform Materials Science and Chemistry: A Reflection on a Large Language Model Hackathon

Chemistry and materials science are complex. Recently, there have been great successes in addressing this complexity using data-driven or computational techniques. Yet, the necessity of input structured in very specific forms and the fact that there is an ever-growing number of tools creates usability and accessibility challenges. Coupled with the reality that much data in these disciplines is unstructured, the effectiveness of these tools is limited. Motivated by recent works that indicated that large language models (LLMs) might help address some of these issues, we organized a hackathon event on the applications of LLMs in chemistry, materials science, and beyond. This article chronicles the projects built as part of this hackathon. Participants employed LLMs for various applications, including predicting properties of molecules and materials, designing novel interfaces for tools, extracting knowledge from unstructured data, and developing new educational applications. The diverse topics and the fact that working prototypes could be generated in less than two days highlight that LLMs will profoundly impact the future of our fields. The rich collection of ideas and projects also indicates that the applications of LLMs are not limited to materials science and chemistry but offer potential benefits to a wide range of scientific disciplines

The Brain Tumor Segmentation (BraTS) Challenge 2023: Focus on Pediatrics (CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs)

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20\%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a landmark community benchmark event with a successful history of 12 years of resource creation for the segmentation and analysis of adult glioma. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which represents the first BraTS challenge focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on benchmarking the development of volumentric segmentation algorithms for pediatric brain glioma through standardized quantitative performance evaluation metrics utilized across the BraTS 2023 cluster of challenges. Models gaining knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training data will be evaluated on separate validation and unseen test mpMRI dataof high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Voriconazole-induced Periostitis

"CASE: A woman in her 60s presented with complaints of severe multifocal bone pain, including the shoulders, sternum, and hips, which had persisted for several months. Two years earlier, the patient had undergone heart transplant for ischemic cardiomyopathy. She had a history of post-transplant AKI on CKD, hypertension, hyperlipidemia, osteoporosis, hypothyroidism and COPD. She was on maintenance immunosuppression with azathioprine, tacrolimus and prednisone. She was on voriconazole for chronic suppression of Bipolaris sp. mediastinitis diagnosed shortly after transplantation and had remained on the antifungal. The patient reported bone pain and a lump on the left clavicle that was palpable on physical examination. Radiograph of the left clavicle can be seen below (Figure 1). Laboratory values demonstrated an elevated creatinine (2.28mg/dL), BUN (35 mg/dL), TSH (2.77 mcunit/mL), alkaline phosphatase (616 units/L), ALT (62 units/L), and AST (67 units/L).Ana Wilden (1), Andres Bran (2) ; 1. School of Medicine, University of Missouri. 2. Division of Infectious Disease, University of Missouri.Includes bibliographical reference

Diagnosis and treatment of moccasin-type/hyperkeratotic tinea pedis

CASE: A man in his 70s was referred to infectious diseases for evaluation of a clinically unresponsive fungal infection. Eight months ago, the patient noticed bilateral erythematous papules and patches on both feet with associated desquamation that worsened over time. His past medical history was non-contributory. Previous treatments included topical ciclopirox, oral fluconazole, oral terbinafine, and a combination of oral terbinafine and topical ciclopirox with no clinical improvement. Itraconazole had been prescribed by his dermatologist: 200mg twice daily for seven days, three weeks off, followed by a repeat course for seven days. The patient noted some improvement but after discontinuation the skin lesions recurred. At this point, the patient was referred to infectious disease, where itraconazole was reinitiated at 300mg twice daily for 6 weeks with resolution of the lesions.Ana Wilden, MHA (The University of Missouri), William V. Stoecker, MD (S and A Technologies), Andres Bran, MD, FACP (Division of Infectious Disease, University of Missouri)Includes bibliographical reference

Disseminated cysticercosis

Case presentation: A 49-year-old male refugee from Uganda with a history significant only for hypothyroidism and hypertension presented to the neurology clinic with an eight-year history of seizures. He has not had a seizure for almost two years while on phenobarbital and phenytoin. He denied any history of parasitic infections or any kind of anti-parasitic treatment in the past. He did not have any headache, fever, nausea, or vomiting but reported intermittent episodes of dizziness. Findings on neurological and general physical examination were normal. Laboratory findings were notable for peripheral eosinophilia and thrombocytopenia present for a few months, which resolved in subsequent evaluations. Human immunodeficiency virus 1/2 Antigen/Antibody (HIV 1/2 Ag/Ab) screen was negative. T1-weighted magnetic resonance imaging (MRI) of his brain showed rim-enhancing cystic lesions in the left frontal and right occipital lobes, left parietal, left temporalis muscle, and left trapezius muscle. The parenchymal lesions were partially calcified. Cysticercosis serum antibody immunoglobulin G (IgG) was negative. Confirmatory immunoblot antibody testing offered by the Center for Disease Control and Prevention (CDC) was positive, supporting the diagnosis of disseminated cysticercosis.Mahilet Assefa, BSc (1), Ayman Nada, MD, Andres Bran, MD (3), Christian Rojas-Moreno, MD (3) ; 1. University of Missouri School of Medicine. 2. Division of Neuroradiology, Department of Radiology, University of Missouri. 3. Division of Infectious Diseases, Department of Medicine, University of Missouri.Includes bibliographical reference

SafeCrow

Code repository for SafeCrow: An approach to safety in chemical synthesis agents.</p

Periodic system converges and is affected by wars

The periodic system emerges by intertwining order and similarity relationships among chemical elements, which in turn arise from known substances at a given time that constitute the chemical space. Although the system has been adjusted to accommodate new elements, the connection with the chemical space has been largely forgotten and the question that arises is about the effect of the exponentially growing chemical space upon the periodic system. To what extent advances in chemistry have confirmed or distorted the periodic system? Is the system --icon of chemistry-- a traversal feature of the chemical space? Here we solve these questions by computationally analysing the effect of the chemical space upon the periodic system from the dawn of the 19th century until the present. We found that although the system has undergone several and significant changes across history, it converges towards a stable structure. This dynamics results from advances in chemistry such as the discovery of elements, of forms of chemical combination and the incorporation of new theoretical frameworks. Interestingly, the periodic system is also influenced by socio-political events such as wars. Given the nature of the chemical space, which holds the inertia of more than 200 years of chemical practice, and the limited chemical possibilities for the remaining elements to be synthesised, we hypothesise that the periodic system is going to remain largely untouched in the years to come. We expect our results and methods trigger further research and discussion in the history, pedagogy, philosophy, and ultimately, in the practice of chemistry