Augmenting large language models with chemistry tools.

Large language models (LLMs) have shown strong performance in tasks across domains but struggle with chemistry-related problems. These models also lack access to external knowledge sources, limiting their usefulness in scientific applications. We introduce ChemCrow, an LLM chemistry agent designed to accomplish tasks across organic synthesis, drug discovery and materials design. By integrating 18 expert-designed tools and using GPT-4 as the LLM, ChemCrow augments the LLM performance in chemistry, and new capabilities emerge. Our agent autonomously planned and executed the syntheses of an insect repellent and three organocatalysts and guided the discovery of a novel chromophore. Our evaluation, including both LLM and expert assessments, demonstrates ChemCrow's effectiveness in automating a diverse set of chemical tasks. Our work not only aids expert chemists and lowers barriers for non-experts but also fosters scientific advancement by bridging the gap between experimental and computational chemistry.

14 examples of how LLMs can transform materials science and chemistry: a reflection on a large language model hackathon.

Large-language models (LLMs) such as GPT-4 caught the interest of many scientists. Recent studies suggested that these models could be useful in chemistry and materials science. To explore these possibilities, we organized a hackathon. 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.

Actinomyces europaeus Brain Abscess in a 69-Year-Old Female Causing Irreversible Neurologic Complications.

Actinomycosis is a chronic, indolent, granulomatous disease process caused by the Actinomyces genus of bacteria. More severe forms of actinomycosis include disseminated or central nervous system (CNS) infections. Actinomyces meyeri is the most common species of Actinomyces isolated from brain abscesses. A. europaeus species is commonly associated with skin and soft tissue abscesses. However, it rarely causes brain abscesses. We present an unusual case of A. europaeus brain abscess in a 69-year-old female who presented with acute encephalopathy and bilateral lower extremity weakness. She was diagnosed with left-sided mastoiditis with intracranial extension, left posterior fossa epidural abscess, and transverse sinus thrombosis. The patient's hospital course was complicated by hydrocephalus and declining neurological status. Empiric antimicrobial therapy was initiated, and the patient underwent mastoidectomy and external ventricular drain placement followed by decompression craniotomy and subarachnoid abscess aspiration. Given her poor and unchanged neurologic status, the patient was transitioned to comfort-oriented measures after shared decision-making with the family. It is crucial to identify Actinomyces as a causal agent of severe CNS infections like brain abscesses, meningoencephalitis, or subdural empyema, as untreated infections can lead to irreversible neurologic complications.

The six stages of the convergence of the periodic system to its final structure.

The periodic system encodes order and similarity among chemical elements arising from known substances at a given time that constitute the chemical space. Although the system has incorporated new elements, the connection with the remaining space is still to be analysed, which leads to the question of how the exponentially growing space has affected the periodic system. Here we show, by analysing the space between 1800 and 2021, that the system has converged towards its current stable structure through six stages, respectively characterised by the finding of elements (1800-1826), the emergence of the core structure of the system (1826-1860), its organic chemistry bias (1860-1900) and its further stabilisation (1900-1948), World War 2 new chemistry (1948-1980) and the system final stabilisation (1980-). Given the self-reinforced low diversity of the space and the limited chemical possibilities of the elements to be synthesised, we hypothesise that the periodic system will remain largely untouched.

CNS Histoplasmosis as a Gliosarcoma mimicker: The diagnostic dilemma of solitary brain lesions.

Histoplasmosis is usually a benign, self-limited disease with lungs predilection. However, it might manifest as a disseminated disease in immunocompromised individuals. The involvement of the central nervous system (CNS) accounts for about 5-10% of cases with disseminated disease. Isolated histoplasmosis of the CNS is rare, and the literature shows only a few reported cases. By imaging studies, it usually presents as an isolated ring-enhancing lesion. Its spectrum of symptoms ranges from acute severe infection to progressive chronic meningitis, which delays the initial diagnosis, correct work-up and initiation of appropriate therapy. We present a case of a 57-year-old man from the Midwest of the United States who misdiagnosed with Gliosarcoma in 2019, for which he underwent appropriate management for Gliosarcoma. Presented for follow-up after new neurological symptoms; worsening in ring-enhancing brain lesions was found on magnetic resonance image MRI. After a re-examination of surgical pathological cases, histoplasmosis of the CNS was diagnosed. Failure of diagnosis CNS histoplasmosis early can lead to poor outcome and decrease chances of recovery.

Herpes Simplex Virus-2 Meningoencephalitis With Abducens Nerve Palsy With Literature Review.

Herpes simplex virus (HSV), a human alpha herpes virus, is responsible for most infections caused by herpes viruses worldwide. Among the herpes simplex viruses, both HSV 1 and 2 cause significant morbidity. HSV-2 accounts for most genital infections with extragenital complications involving the groin, thigh, or other pelvic areas. HSV-2 is the leading viral cause of sexually transmitted diseases. Viral dissemination via the blood or the cutaneous route during primary infection can affect joints, liver, lungs, spinal cord, and brain. HSV-2, by nature of its higher reactivation frequency, leads to clinical reactivation or subclinical shedding, resulting in increased transmission risk during unprotected sexual encounters. HSV-2 reactivation can result in lesions involving the fingers, skin, eyes, brain, and visceral organs such as the esophagus, lung, and liver. Ocular involvement results in keratitis, blepharitis, conjunctivitis, and rarely necrotizing retinitis. Oculomotor cranial nerve involvement by HSV is a rare entity even in patients with human immunodeficiency virus infection. Clinical features associated with reactivation are seen in primary infections, especially in children and adolescents. A medical literature search resulted in a few cases caused by a varicella-zoster virus but none by HSV. Here we describe a young female with a newly diagnosed meningoencephalitis and abducens nerve palsy (first case) due to a primary HSV infection. She came to the emergency department with headache, confusion, abnormal behavior and later developed diplopia as an inpatient. She was treated successfully with two weeks of acyclovir.

Cytomegalovirus pneumonitis-induced secondary hemophagocytic lymphohistiocytosis and SIADH in an immunocompetent elderly male literature review.

Hemophagocytic lymphohistiocytosis (HLH) is also known as hemophagocytic syndrome. It is a lethal hematologic condition due to a dysregulated immune response which results in inappropriately activated macrophages damaging host tissues. Based on the etiology, HLH can be primary (genetic) or secondary (acquired). The most common cause of a secondary HLH is an infection. Viral infections are the most common cause of secondary HLH. Among the viral causes of secondary HLH, Epstein-Barr virus is the most common etiologic agent. Cytomegalovirus (CMV) is a common causative pathogen in the immunocompromised host but is rare in an immunocompetent adult. In infection- associated secondary HLH, treatment includes antimicrobial therapy. HLH carries a high mortality and morbidity rate as it is an underdiagnosed clinical condition. Successful early diagnosis allows for adequate time for curative therapy. Treatment for HLH includes chemotherapy, immunomodulators, and a hematopoietic stem-cell transplant. The 2004 diagnostic criteria set by the Histiocyte Society serves as a guide to make an earlier clinical diagnosis. A review of PubMed literature revealed only five reported cases of CMV-induced HLH. We describe the sixth case of CMV pneumonitis-induced HLH and syndrome of inappropriate antidiuretic hormone secretion in a 72-year-old White male. He was treated successfully with oral valganciclovir and corticosteroids.

Primary cutaneous cryptococcal infection due to fingolimod - Induced lymphopenia with literature review.

Cryptococcus. Neoformans (C. neoformans) is an encapsulated heterobasidiomycetous fungus responsible for opportunistic infections worldwide in immunocompromised patients. Clinical presentation ranges from asymptomatic respiratory tract colonization to disseminated infection in any human body part. The central nervous system (CNS) and pulmonary diseases garner most of the clinical attention. Secondary cutaneous cryptococcosis is an uncommon manifestation seen as a sentinel sign commonly in disseminated cryptococcal infection. Primary cutaneous cryptococcosis (PCC) is a rare manifestation seen in both immunocompromised and immunocompetent patients. It is a discrete infection with different epidemiological trends. Immunosuppressive therapy (corticosteroids, tacrolimus) predisposes a patient to acquire this clinical entity. We present a case of an elderly Caucasian male on fingolimod for relapsing-remitting multiple sclerosis with nonhealing scalp lesions for four years. He was a referral to our healthcare center for the presence of fungal elements seen on a scalp biopsy fungal stains. Final cultures returned positive for C. neoformans susceptible to fluconazole (MIC = 8 µg/mL). The CD4 count was 13 cells/uL, and workup for CNS and disseminated cryptococcal infection were negative. Fingolimod is an immunomodulator that acts on sphingosine 1-phosphate receptors, affecting the lymphocytes. Pubmed literature review revealed few case reports (< 5) with PCC in patients on fingolimod. To our knowledge, ours is the first case with scalp cryptococcosis, with the lowest CD4 count while being on fingolimod. No randomized controlled trial data exist for the treatment of PCC. Therapy initiated with oral luconazole for six months with significant improvement at three months.

Cervical cancer screening among HIV-infected women in an urban, United States safety-net healthcare system.

OBJECTIVE: Little is known about cervical cancer screening and results patterns among HIV-infected (HIV+) women in real-world healthcare settings. We characterized two periods of screening opportunity. DESIGN: Retrospective cohort. SETTING: US safety-net healthcare system in Dallas County, Texas. PARTICIPANTS: We analyzed data from electronic medical records (EMR) of 1490 HIV+ women receiving care 2010-2014. MAIN OUTCOME MEASURES: At baseline, we categorized a woman's Pap status 15 months prior to index date as under-screened (vs. screened), and cytology result (normal vs. abnormal). Then, we examined screening completion and results, and colposcopy uptake and results after an abnormal screen, in the subsequent 15-month period. RESULTS: More than half of women (56%) had no evidence of a Pap test (i.e. under-screened) at baseline. Under-screened women were more likely to be older (50-64 years), have diabetes, and unknown viral load; they were less likely to be Black, Hispanic, have Medicaid, recently pregnant, have a HIV clinic visit, or a CD4 cell count at least 200 cells/µl. Nearly half of under-screened women (46%, n = 383) remained under-screened in the subsequent 15 months. Among women under-screened at baseline who later completed screening and follow-up during the study period, 21 high-grade dysplasia and three cancers were diagnosed. Overall, 40% of women did not receive colposcopy when needed, with most failures to follow-up occurring in women who were under-screened at baseline. CONCLUSION: Most HIV+ women receiving care in a safety-net system did not receive sufficient screening for cervical cancer and remained at exceptionally high risk of developing high-grade dysplasia.