Gene-Environment Interactions: My Unique Journey.

I am deeply honored to be invited to write this scientific autobiography. As a physician-scientist, pediatrician, molecular biologist, and geneticist, I have authored/coauthored more than 600 publications in the fields of clinical medicine, biochemistry, biophysics, pharmacology, drug metabolism, toxicology, molecular biology, cancer, standardized gene nomenclature, developmental toxicology and teratogenesis, mouse genetics, human genetics, and evolutionary genomics. Looking back, I think my career can be divided into four distinct research areas, which I summarize mostly chronologically in this article: (a) discovery and characterization of the AHR/CYP1 axis, (b) pharmacogenomics and genetic prediction of response to drugs and other environmental toxicants, (c) standardized drug-metabolizing gene nomenclature based on evolutionary divergence, and (d) discovery and characterization of the SLC39A8 gene encoding the ZIP8 metal cation influx transporter. Collectively, all four topics embrace gene-environment interactions, hence the title of my autobiography.

Ambiviricota, a novel ribovirian phylum for viruses with viroid-like properties.

Fungi harbor a vast diversity of mobile genetic elements (MGEs). Recently, novel fungal MGEs, tentatively referred to as 'ambiviruses,' were described. 'Ambiviruses' have single-stranded RNA genomes of about 4-5 kb in length that contain at least two open reading frames (ORFs) in non-overlapping ambisense orientation. Both ORFs are conserved among all currently known 'ambiviruses,' and one of them encodes a distinct viral RNA-directed RNA polymerase (RdRP), the hallmark gene of ribovirian kingdom Orthornavirae. However, 'ambivirus' genomes are circular and predicted to replicate via a rolling-circle mechanism. Their genomes are also predicted to form rod-like structures and contain ribozymes in various combinations in both sense and antisense orientations-features reminiscent of viroids, virusoids, ribozyvirian kolmiovirids, and yet-unclassified MGEs (such as 'epsilonviruses,' 'zetaviruses,' and some 'obelisks'). As a first step toward the formal classification of 'ambiviruses,' the International Committee on Taxonomy of Viruses (ICTV) recently approved the establishment of a novel ribovirian phylum, Ambiviricota, to accommodate an initial set of 20 members with well-annotated genome sequences.

Changes in fungal taxonomy: mycological rationale and clinical implications.

Numerous fungal species of medical importance have been recently subjected to and will likely continue to undergo nomenclatural changes as a result of the application of molecular approaches to fungal classification together with abandonment of dual nomenclature. Here, we summarize those changes affecting key groups of fungi of medical importance, explaining the mycological (taxonomic) rationale that underpinned the changes and the clinical relevance/importance (where such exists) of the key nomenclatural revisions. Potential mechanisms to mitigate unnecessary taxonomic instability are suggested, together with approaches to raise awareness of important changes to minimize potential clinical confusion.

"Deoxy" to be or "Desoxy" not to be-a century-old tale in the history of DNA nomenclature.

This commentary discusses a comprehensive history of the first-ever use of pertinent words directly related to DNA, such as desoxyribose, deoxyribose, desoxyribonucleic acid, and deoxyribonucleic acid. With almost 100 years of the identification and nomenclature of desoxyribose sugar and desoxyribonucleic acid, the term "desoxy" continues to see limited use. We hope that whenever young researchers come across the sporadic occurrence of "desoxy" in any published text, they will not consider it a mistake.

A guide to naming human non-coding RNA genes.

Research on non-coding RNA (ncRNA) is a rapidly expanding field. Providing an official gene symbol and name to ncRNA genes brings order to otherwise potential chaos as it allows unambiguous communication about each gene. The HUGO Gene Nomenclature Committee (HGNC, www.genenames.org) is the only group with the authority to approve symbols for human genes. The HGNC works with specialist advisors for different classes of ncRNA to ensure that ncRNA nomenclature is accurate and informative, where possible. Here, we review each major class of ncRNA that is currently annotated in the human genome and describe how each class is assigned a standardised nomenclature.

Twenty years of big plant genera.

In 2004, David Frodin published a landmark review of the history and concepts of big plant genera. Two decades of taxonomic activity have taken place since, coinciding with a revolution in phylogenetics and taxonomic bioinformatics. Here we use data from the World Flora Online (WFO) to provide an updated list of big (more than 500 species) and megadiverse (more than 1000 species) flowering plant genera and highlight changes since 2004. The number of big genera has increased from 57 to 86; today one of every four plant species is classified as a member of a big genus, with 14% in just 28 megadiverse genera. Most (71%) of the growth in big genera since 2000 is the result of new species description, not generic re-circumscription. More than 15% of all currently accepted flowering plant species described in the last two decades are in big genera, suggesting that groups previously considered intractable are now being actively studied taxonomically. Despite this rapid growth in big genera, they remain a significant yet understudied proportion of plant diversity. They represent a significant proportion of global plant diversity and should remain a priority not only for taxonomy but for understanding global diversity patterns and plant evolution in general.

How to classify antipsychotics: time to ditch dichotomies?

The dichotomies of 'typical/atypical' or 'first/second generation' have been employed for several decades to classify antipsychotics, but justification for their use is not clear. In the current analysis we argue that this classification is flawed from both clinical and pharmacological perspectives. We then consider what approach should ideally be employed in both clinical and research settings.

Formation of prokaryote names from personal names: a review of current practice and a proposal to emend Appendix 9 of the International Code of Nomenclature of Prokaryotes.

The practice of naming elements from the natural world after notable individuals stretches back to ancient times. This practice of creating eponyms-terms derived from personal names-has been carried forward into prokaryotic nomenclature, where the International Code of Nomenclature of Prokaryotes (ICNP) sets guidelines for creating scientific names from personal names. However, these guidelines can be seen as culturally biased, disjointed and, on occasion, misguided. Here, with the goal of modernizing these recommendations to render them more user-friendly, coherent and inclusive, I review current practice in the light of precedents and key linguistic and cultural principles, while questioning the applicability of the first-name/last-name paradigm for many cultural traditions. Procedural challenges include romanization of the personal name (including handling of diacritics), creation of a short and agreeable latinized stem, assignment of the stem to a declension and addition of suffixes or compound word components to create genus names or species epithets, customizing the approach for names and stems that end in a vowel. I review the pros and cons of stem augmentation, which involves addition of an extra 'i' to the original stem. Next, I formulate a coherent workflow, which I incorporate into a Python script to enable computer-based automation of name creation. Rather than following the ICNP in limiting discussion to a few dozen mainly European names, I examine how these principles work out when applied to the tens of thousands of last names under which scientists publish in the PubMed database, focusing on edge cases where conventional approaches fail, particularly very short and very long names. Drawing on these explorations and analyses, I propose emendations to the advice currently presented in the ICNP to usher in a modern, consistent, pragmatic and globally inclusive approach to the creation of prokaryotic eponyms.

Valid publication of names for bacterial species from the chicken gut.

This article is a follow-up to Gilroy R, Ravi A, Getino M, Pursley I, Horton DL, et al. PeerJ 2021;9:e10941, detailing accession numbers from culture collections to ensure that names for 33 new species conform to the Rules of the International Code of Nomenclature of Prokaryotes required for valid publication of names for cultured species. The following species names are now proposed to be recognized as validly published: Acinetobacter pecorum sp. nov., Arthrobacter gallicola sp. nov., Arthrobacter pullicola sp. nov., Bacillus norwichensis sp. nov., Brevibacterium gallinarum sp. nov., Brevundimonas guildfordensis sp. nov., Cellulomonas avistercoris sp. nov., Clostridium gallinarum sp. nov., Comamonas avium sp. nov., Corynebacterium gallinarum sp. nov., Cytobacillus stercorigallinarum sp. nov., Escherichia whittamii sp. nov., Kaistella pullorum sp. nov., Luteimonas colneyensis sp. nov., Microbacterium commune sp. nov., Microbacterium gallinarum sp. nov., Microbacterium pullorum sp. nov., Oceanitalea stevensii sp. nov., Ochrobactrum gallinarum sp. nov., Oerskovia douganii sp. nov., Oerskovia gallyi sp. nov., Oerskovia merdavium sp. nov., Oerskovia rustica sp. nov., Paenibacillus gallinarum sp. nov., Phocaeicola gallinarum sp. nov., Planococcus wigleyi sp. nov., Psychrobacter communis sp. nov., Serpens gallinarum sp. nov., Solibacillus faecavium sp. nov., Sporosarcina gallistercoris sp. nov., Sporosarcina quadrami sp. nov., Stenotrophomonas pennii sp. nov. and Ureibacillus galli sp. nov.

Proposals to revise the Statutes of the International Committee on Systematics of Prokaryotes.

The International Committee on Systematics of Prokaryotes serves to administer the rules of prokaryotic nomenclature via the International Code of Nomenclature of Prokaryotes, ensures the publication of the International Journal of Systematic and Evolutionary Microbiology, and works to represent the interests of the microbiological disciplines regarding prokaryotic nomenclature. The functions and mechanisms of operation of the International Committee on Systematics of Prokaryotes (ICSP) are defined in its Statutes, which were last revised in 2019. As members of the 2020-2023 and the 2023-2026 ICSP Executive Board and the Judicial Commission, we propose here some further revisions to help improve the clarity and functionality of the Statutes.

Judicial Opinion 129.

Opinion 129 addresses the status of Firmicutes corrig. Gibbons and Murray 1978 (Approved Lists 1980). The name has the category 'division' and was included in the Approved Lists of Bacterial Names, although that category had previously been removed from the International Code of Nomenclature of Bacteria (1975 revision onwards). When the category 'phylum' was introduced into the International Code of Nomenclature of Prokaryotes (ICNP) in 2021, equivalence between 'phylum' and 'division' was not stipulated. Since the definition of the taxonomic categories and their relative order is one of the principal tasks of every code of nomenclature, the inclusion of Firmicutes corrig. Gibbons and Murray 1978 in the Approved Lists was an error. The name is either not validly published or illegitimate because its category is not covered by the ICNP. If Firmicutes corrig. Gibbons and Murray 1978 (Approved Lists 1980) was a validly published phylum name, it would be illegitimate because it would contravene Rule 8, which does not permit any deviation from the requirement to derive a phylum name from the name of the type genus. Since Firmicutes corrig. Gibbons and Murray 1978 is also part of a 'misfitting megaclassification' recognized in Opinion 128, the name is rejected, without any pre-emption regarding a hypothetically validly published name Firmicutes at the rank of phylum. Gracilicutes Gibbons and Murray 1978 (Approved Lists 1980) and Anoxyphotobacteriae Gibbons and Murray 1978 (Approved Lists 1980) are also rejected. The validly published phylum names have a variety of advantages over their not validly published counterparts and cannot be replaced with ad hoc names suggested in the literature. To ease the transition, it is recommended to mention the not validly published phylum names which strongly deviate in spelling from their validly published counterparts along with the latter in publications during the next years.

Is the bacterial genus name Rhodococcus Zopf 1891 illegitimate? Request for an Opinion.

In 2014, it was reported that the bacterial genus name Rhodococcus Zopf 1891 was illegitimate due to the priority of the cyanobacterial genus name Rhodococcus Hansgirg 1884. Since that time, the consequences of this conclusion have been largely ignored, whilst changes have been made to relevant Rules of the International Code of Nomenclature of Prokaryotes, including significant changes to the way in which the Code treats the names of members of Cyanobacteriota. Given the complexity of the nomenclatural issues, we request the opinion of the Judicial Commission of the International Committee on Systematics of Prokaryotes as to whether the genus name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate.

Valid publication of names of two domains and seven kingdoms of prokaryotes.

The International Code of Nomenclature of Prokaryotes (ICNP) now includes the categories domain and kingdom. For the purpose of the valid publication of their names under the ICNP, we consider here the two known domains, 'Bacteria' and 'Archaea', as well as a number of taxa suitable for the rank of kingdom, based on previous phylogenetic and taxonomic studies. It is proposed to subdivide the domain Bacteria into the kingdoms Bacillati, Fusobacteriati, Pseudomonadati and Thermotogati. This arrangement reflects contemporary phylogenetic hypotheses as well as previous taxonomic proposals based on cell wall structure, including 'diderms' vs. 'monoderms', Gracilicutes vs. Firmicutes, 'Negibacteria' vs. 'Unibacteria', 'Hydrobacteria' vs. 'Terrabacteria', and 'Hydrobacterida' vs. 'Terrabacterida'. The domain Archaea is proposed to include the kingdoms Methanobacteriati, Nanobdellati and Thermoproteati, reflecting the previous division into 'Euryarchaeota', 'DPANN superphylum' and 'TACK superphylum'.

Emendation of Appendix 9 of the International Code of Nomenclature of Prokaryotes to provide guidelines for naming genera after geographical locations.

Following a proposal to emend Appendix 9 of the International Code of Nomenclature of Prokaryotes with guidelines for the naming of genera after geographical locations, I here report the outcome of the ballot on this proposal by the members of the International Committee on Systematics of Prokaryotes and present the guidelines to be incorporated in Appendix 9.

Proposal of three novel insect-associated Commensalibacter species: Commensalibacter melissae sp. nov., Commensalibacter communis sp. nov. and Commensalibacter papalotli sp. nov.

A recent modification of the Note to Rule 25a of the International Code for Nomenclature of Bacteria is used a posteriori by the List Editors of the International Journal of Systematic and Evolutionary Microbiology to justify the refusal to validate species protologues published in supplementary material prior to this formal decision. Authors are therefore forced to ask permission to reuse published data for the valid publication of such names. In the present letter we re-publish the species protologues of Commensalibacter melissae sp. nov., Commensalibacter communis sp. nov. and Commensalibacter papalotli sp. nov.

The yeast genus Tardiomyces gen. nov. with one new species and two new combinations.

PURPOSE: Rare yeasts species are increasingly reported as causative agents of invasive human infection. Proper identification and antifungal therapy are essential to manage these infections. Candida blankii is one of these emerging pathogens and is known for its reduced susceptibility to multiple antifungals. METHODS: To obtain more insight into the characteristics of this species, 26 isolates reported as C. blankii were investigated using genetic and phenotypical approaches. RESULTS: Among the 26 isolates, seven recovered either from blood, sputum, urine, or the oral cavity, displayed substantial genetic and some phenotypical differences compared to the other isolates, which were confirmed as C. blankii. We consider these seven strains to represent a novel species, Tardiomyces depauwii. Phylogenomics assigned C. blankii, C. digboiensis, and the novel species in a distinct branch within the order Dipodascales, for which the novel genus Tardiomyces is erected. The new combinations Tardiomyces blankii and Tardiomyces digboiensis are introduced. Differences with related, strictly environmental genera Sugiyamaella, Crinitomyces, and Diddensiella are enumerated. All three Tardiomyces species share the rare ability to grow up to 42 °C, display slower growth in nutrient-poor media, and show a reduced susceptibility to azoles and echinocandins. Characteristics of T. depauwii include high MIC values with voriconazole and a unique protein pattern. CONCLUSION: We propose the novel yeast species Tardiomyces depauwii and the transfer of C. blankii and C. digboiensis to the novel Tardiomyces genus.

Predicting concrete strength early age using a combination of machine learning and electromechanical impedance with nano-enhanced sensors.

To ensure the structural integrity of concrete and prevent unanticipated fracturing, real-time monitoring of early-age concrete's strength development is essential, mainly through advanced techniques such as nano-enhanced sensors. The piezoelectric-based electro-mechanical impedance (EMI) method with nano-enhanced sensors is emerging as a practical solution for such monitoring requirements. This study presents a strength estimation method based on Non-Destructive Testing (NDT) Techniques and Long Short-Term Memory (LSTM) and artificial neural networks (ANNs) as hybrid (NDT-LSTMs-ANN), including several types of concrete strength-related agents. Input data includes water-to-cement rate, temperature, curing time, and maturity based on interior temperature, allowing experimentally monitoring the development of concrete strength from the early steps of hydration and casting to the last stages of hardening 28 days after the casting. The study investigated the impact of various factors on concrete strength development, utilizing a cutting-edge approach that combines traditional models with nano-enhanced piezoelectric sensors and NDT-LSTMs-ANN enhanced with nanotechnology. The results demonstrate that the hybrid provides highly accurate concrete strength estimation for construction safety and efficiency. Adopting the piezoelectric-based EMI technique with these advanced sensors offers a viable and effective monitoring solution, presenting a significant leap forward for the construction industry's structural health monitoring practices.

A review of recently introduced Aspergillus, Penicillium, Talaromyces and other Eurotiales species.

The order Eurotiales is diverse and includes species that impact our daily lives in many ways. In the past, its taxonomy was difficult due to morphological similarities, which made accurate identification of species difficult. This situation improved and stabilised with recent taxonomic and nomenclatural revisions that modernised Aspergillus, Penicillium and Talaromyces. This was mainly due to the availability of curated accepted species lists and the publication of comprehensive DNA sequence reference datasets. This has also led to a sharp increase in the number of new species described each year with the accepted species lists in turn also needing regular updates. The focus of this study was to review the 160 species described between the last list of accepted species published in 2020 until 31 December 2022. To review these species, single-gene phylogenies were constructed and GCPSR (Genealogical Concordance Phylogenetic Species Recognition) was applied. Multi-gene phylogenetic analyses were performed to further determine the relationships of the newly introduced species. As a result, we accepted 133 species (37 Aspergillus, two Paecilomyces, 59 Penicillium, two Rasamsonia, 32 Talaromyces and one Xerochrysium), synonymised 22, classified four as doubtful and created a new combination for Paraxerochrysium coryli, which is classified in Xerochrysium. This brings the number of accepted species to 453 for Aspergillus, 12 for Paecilomyces, 535 for Penicillium, 14 for Rasamsonia, 203 for Talaromyces and four for Xerochrysium. We accept the newly introduced section Tenues (in Talaromyces), and series Hainanici (in Aspergillus sect. Cavernicolarum) and Vascosobrinhoana (in Penicillium sect. Citrina). In addition, we validate the invalidly described species Aspergillus annui and A. saccharicola, and series Annuorum (in Aspergillus sect. Flavi), introduce a new combination for Dichlaena lentisci (type of the genus) and place it in a new section in Aspergillus subgenus Circumdati, provide an updated description for Rasamsonia oblata, and list excluded and recently synonymised species that were previously accepted. This study represents an important update of the accepted species lists in Eurotiales. Taxonomic novelties: New sections: Aspergillus section Dichlaena Visagie, Kocsubé & Houbraken. New series: Aspergillus series Annuorum J.J. Silva, B.T. Iamanaka, Frisvad. New species: Aspergillus annui J.J. Silva, M.H.P. Fungaro, Frisvad, M.H. Taniwaki & B.T. Iamanaka; Aspergillus saccharicola J.J. Silva, Frisvad, M.H.P. Fungaro, M.H. Taniwaki & B.T. Iamanaka. New combinations: Aspergillus lentisci (Durieu & Mont.) Visagie, Malloch, L. Kriegsteiner, Samson & Houbraken; Xerochrysium coryli (Crous & Decock) Visagie & Houbraken. Citation: Visagie CM, Yilmaz N, Kocsubé S, Frisvad JC, Hubka V, Samson RA, Houbraken J (2024). A review of recently introduced Aspergillus, Penicillium, Talaromyces and other Eurotiales species. Studies in Mycology 107: 1-66. doi: 10.3114/sim.2024.107.01.

Identification of Predictors for Clinical Deterioration in Patients With COVID-19 via Electronic Nursing Records: Retrospective Observational Study.

BACKGROUND: Few studies have used standardized nursing records with Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) to identify predictors of clinical deterioration. OBJECTIVE: This study aims to standardize the nursing documentation records of patients with COVID-19 using SNOMED CT and identify predictive factors of clinical deterioration in patients with COVID-19 via standardized nursing records. METHODS: In this study, 57,558 nursing statements from 226 patients with COVID-19 were analyzed. Among these, 45,852 statements were from 207 patients in the stable (control) group and 11,706 from 19 patients in the exacerbated (case) group who were transferred to the intensive care unit within 7 days. The data were collected between December 2019 and June 2022. These nursing statements were standardized using the SNOMED CT International Edition released on November 30, 2022. The 260 unique nursing statements that accounted for the top 90% of 57,558 statements were selected as the mapping source and mapped into SNOMED CT concepts based on their meaning by 2 experts with more than 5 years of SNOMED CT mapping experience. To identify the main features of nursing statements associated with the exacerbation of patient condition, random forest algorithms were used, and optimal hyperparameters were selected for nursing problems or outcomes and nursing procedure-related statements. Additionally, logistic regression analysis was conducted to identify features that determine clinical deterioration in patients with COVID-19. RESULTS: All nursing statements were semantically mapped to SNOMED CT concepts for "clinical finding," "situation with explicit context," and "procedure" hierarchies. The interrater reliability of the mapping results was 87.7%. The most important features calculated by random forest were "oxygen saturation below reference range," "dyspnea," "tachypnea," and "cough" in "clinical finding," and "oxygen therapy," "pulse oximetry monitoring," "temperature taking," "notification of physician," and "education about isolation for infection control" in "procedure." Among these, "dyspnea" and "inadequate food diet" in "clinical finding" increased clinical deterioration risk (dyspnea: odds ratio [OR] 5.99, 95% CI 2.25-20.29; inadequate food diet: OR 10.0, 95% CI 2.71-40.84), and "oxygen therapy" and "notification of physician" in "procedure" also increased the risk of clinical deterioration in patients with COVID-19 (oxygen therapy: OR 1.89, 95% CI 1.25-3.05; notification of physician: OR 1.72, 95% CI 1.02-2.97). CONCLUSIONS: The study used SNOMED CT to express and standardize nursing statements. Further, it revealed the importance of standardized nursing records as predictive variables for clinical deterioration in patients.

Perceptions on and roadblocks to implementation of standardized nomenclature in radiation oncology: A survey from TG-263U1.

PURPOSE: AAPM Task Group No. 263U1 (Update to Report No. 263 - Standardizing Nomenclatures in Radiation Oncology) disseminated a survey to receive feedback on utilization, gaps, and means to facilitate further adoption. METHODS: The survey was created by TG-263U1 members to solicit feedback from physicists, dosimetrists, and physicians working in radiation oncology. Questions on the adoption of the TG-263 standard were coupled with demographic information, such as clinical role, place of primary employment (e.g., private hospital, academic center), and size of institution. The survey was emailed to all AAPM, AAMD, and ASTRO members. RESULTS: The survey received 463 responses with 310 completed survey responses used for analysis, of whom most had the clinical role of medical physicist (73%) and the majority were from the United States (83%). There were 83% of respondents who indicated that they believe that having a nomenclature standard is important or very important and 61% had adopted all or portions of TG-263 in their clinics. For those yet to adopt TG-263, the staffing and implementation efforts were the main cause for delaying adoption. Fewer respondents had trouble adopting TG-263 for organs at risk (29%) versus target (44%) nomenclature. Common themes in written feedback were lack of physician support and available resources, especially in vendor systems, to facilitate adoption. CONCLUSIONS: While there is strong support and belief in the benefit of standardized nomenclature, the widespread adoption of TG-263 has been hindered by the effort needed by staff for implementation.  Feedback from the survey is being utilized to drive the focus of the update efforts and create tools to facilitate easier adoption of TG-263.