Dental anesthesiology: its history and continuing evolution. Niels Bjorn Jorgensen 2nd memorial lecture.
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Anesthesia, Dental↗
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Results for “Continuous Evolution”
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The continued evolution of the University of Miami/Jackson Memorial Medical Center.
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Academic Medical Centers↗
Orthogonal replication with optogenetic selection evolves yeast JEN1 into a mevalonate transporter.
The in vivo continuous evolution system OrthoRep (orthogonal replication) is a powerful strategy for rapid enzyme evolution in Saccharomyces cerevisiae that diversifies genes at a rate exceeding the endogenous genome mutagenesis rate by several orders of magnitude. However, it is difficult to neofunctionalize genes using OrthoRep partly because of the way selection pressures are applied. Here we combine OrthoRep with optogenetics in a selection strategy we call OptoRep, which allows fine-tuning of selection pressure with light. With this capability, we evolved a truncated form of the endogenous monocarboxylate transporter JEN1 (JEN1t) into a de novo mevalonate importer. We demonstrate the functionality of the evolved JEN1t (JEN1tY180C/G) in the production of farnesene, a renewable aviation biofuel, from mevalonate fed to fermentation media or produced by microbial consortia. This study shows that the light-induced complementation of OptoRep may improve the ability to evolve functions not currently accessible for selection, while its fine tunability of selection pressure may allow the continuous evolution of genes whose desired function has a restrictive range between providing effective selection and cellular viability.
Saccharomyces cerevisiae↗
Continuing education: evolution or revolution: II. What about the future?
Having previously written something about the 'roots' of the radiologic technology profession, the author now concentrates on where it goes from here. What are the implications of the demand for accountability on the educational process? How does it adjust to changing technology? What are the future career prospects? How does the profession meet manpower challenges? Who pays the bills? Because the future cannot be completely defined in the present, this article necessarily asks more questions than it answers, but seeks input into the decision-making process from those who are most affected by it--radiologic technologists.
Attitude↗
The evolution of continuous variation. II. complex transmission and assortative mating.
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Environment↗
Some observations and hypotheses about the psychoanalytic theory of adult development.
The developmental framework, when applied to adulthood, emphasizes the continuing evolution of the personality at five or fifty and 'focuses on the formation of psychic structure in process and underscores the continuity of normal and pathologic outcomes.' (COPER 9, 1974, p. 14). Many of the events we have discussed here are experiences unique to the adult and outside the realm of the child. Their uniqueness and developmental significance need to be better accounted for in psychoanalytic theory. Confrontation with each adult developmental task or crisis produces basic change in the life of each individual. To quote Bibring (1959): 'We find them as developmental phenomena at points of no return between one phase and the next when decisive changes deprive former central needs and modes of living of their significance forcing the acceptance of highly charged new goals and functions.' (p. 119). One purpose of this paper has been to demonstrate that such developmental turning points of no return are not limited to childhood but occur throughout the life cycle.
Adult↗
Transgenerational continuity: Persistence as a dimension of inheritance and evolution.
Transgenerational continuity (TC) describes the persistence of inherited molecular architectures across generations. Progress in identity-by-descent (IBD) detection, recombination dynamics, and epigenetic research highlights the growing need for a more comprehensive model of inheritance. This theoretical framework synthesizes evidence from genomics, population studies, and epigenetics to outline how inherited molecular architectures, which are transmitted through IBD, together with heritable epigenetic modifications, can preserve ancestral information across generations. IBD captures genomic continuity across three nested scales, where recent familial segments link close relatives, population-level haplotypes are shared across cohorts, and archaic fragments from Neanderthal and Denisovan admixture persist as molecular fossils of ancient lineages. Although recombination and selection reshape these regions, their persistence across time scales highlights the evolutionary durability of genomic continuity. Epigenetic memory reflects regulatory persistence, whereby molecular modifications can preserve functional states across cell divisions and sometimes across generations. Together with familial and population-level IBD persistence and the long-term retention of introgressed haplotypes, these findings demonstrate that inherited molecular architectures can persist across multiple timescales. Evolutionary processes shape this persistence. Purifying selection preferentially removes deleterious inherited variants, whereas positive selection can favor the persistence of functionally relevant genomic architectures. From this perspective, evolutionary dynamics arise not only from the generation of variation, but also from the differential persistence of inherited molecular architectures through selection. Transgenerational continuity therefore provides a conceptual framework in which persistence serves as an explanatory dimension of inheritance and evolution that complements variation and explains the persistence of biological identity across generations and evolutionary time.
Biological identity↗
Sequelae of stomach surgery.
Gastric surgery has undergone continuous evolution since the 19th century. At present it is a highly sophisticated technique which provides symptomatic relief for the vast majority of patients operated upon for peptic ulcer disease. Although the overall incidence of complications has decreased, a variety of complications continues to occur and radiological examination plays a critical role in their detection, evaluation, and management. Knowledge of the variations in surgical terminology and commonly used eponyms provides the basic framework for discussion. Familiarity with the radiological appearance of the normal postoperative stomach together with an understanding of its physiology are essential prerequisites to the recognition of possible complications. Operative techniques may result in a radiographic appearance which simulates disease. Conditions as diverse as bezoars, afferent and efferent loop problems, marginal ulceration, anastomotic leakage, prolapse, and intussuception may all be characterized by distinct and highly specific radiographic changes. Physiologic problems such as dumping and malabsorption may also reflect their presence by X-ray changes. The radiographic features in a large number of surgical complications are discussed and illustrated. The importance of the radiographic examination in the postsurgical stomach is emphasized.
Digestive System↗
Gastric carcinoma classification in the WHO 6th edition (2026): Updated framework and emerging entities.
The sixth edition of the WHO Classification of Digestive System Tumours (2026) represents an important step in the continuing evolution of gastric carcinoma classification. While preserving morphology as the foundation of diagnosis, it incorporates advances in molecular pathology, genotype-phenotype correlations, tumour evolution, and predictive biomarker assessment. This review summarizes the development of the WHO classification from the third edition (2000) to the sixth edition (2026) and highlights its relationship with other major classification systems, including those of Laurén, Nakamura, and the Japanese Gastric Carcinoma Association (JGCA). Major histological categories remain largely unchanged; however, several important conceptual and diagnostic refinements have been introduced. These include recognition of crawling-type adenocarcinoma as a distinctive variant of tubular adenocarcinoma, subclassification of poorly cohesive carcinoma into signet-ring cell and non-signet-ring cell subtypes, introduction of the concept of pure signet-ring cell carcinoma, and increased emphasis on tumour evolution. The sixth edition also expands and refines the spectrum of uncommon gastric carcinoma subtypes, including gastric carcinoma with lymphoid stroma, AFP-producing carcinoma, micropapillary adenocarcinoma, gastric adenocarcinoma of fundic-gland type, and gastric sarcomatoid carcinoma. Crucially, molecular subgroups originally proposed by The Cancer Genome Atlas (TCGA) and actionable biomarkers-including HER2 (ERBB2), Claudin 18.2, mismatch repair deficiency/microsatellite instability (dMMR/MSI), and programmed death-ligand 1 (PD-L1)-have transitioned from research-based categories into essential tools for precision oncology. Rather than providing exhaustive diagnostic criteria, this review offers a conceptual framework and encourages consultation of the original WHO text for full details. These advances illustrate the transition of gastric carcinoma classification from a predominantly morphology-based system toward an integrated histomolecular framework that more closely links pathological diagnosis with tumour biology, prognostication, and therapeutic stratification.
Crawling-type adenocarcinoma↗
Behavioral marriage therapy. III. The contents of Gurman et al. may be hazardous to our health.
This paper was written as a reply to a critique of behavioral marital therapy (BMT) by Gurman, Kniskern, and Knudson (6, 7). The reply is divided into four sections. First, the paper addresses the critics' comments on the conceptual model put forth by BMT, correcting and clarifying various misconceptions, and restating some of the basic ideological principles in the behavioral model. Second, the paper discusses behavioral change techniques and technology, along with extratechnological treatment considerations. Again, misrepresentations of BMT are corrected. Third, an analysis of the literature investigating the therapeutic efficacy of BMT is reviewed, and the conclusion is reached that BMT is demonstrably effective, at least for a substantial number of mildly to moderately distressed couples. Criticisms are made of the analysis of the same literature conducted by Gurman et al. We conclude that, contrary to the spirit of the paper by Gurman et al., BMT is a viable framework for conceptualizing and treating relationship problems and that the commitment of its adherents to experimental investigation promises continued evolution, refinement, and improvement.
Behavior Therapy↗
Coxsackievirus A6 on the rise: epidemiology, pathogenicity, evolutionary dynamics, and antiviral strategy.
SUMMARYIn recent years, coxsackievirus A6 (CVA6) has become a predominant cause of hand, foot, and mouth disease (HFMD) worldwide, surpassing enterovirus A71 (EV-A71) and CVA16. The rise of CVA6 is of particular public health concern due to its association with atypical and severe clinical presentations, including extensive vesiculobullous eruptions and neurological complications. These diverse and often non-classical manifestations, which also occur in adults, complicate clinical diagnosis and highlight the need for enhanced molecular surveillance. Furthermore, the potential impact of enteroviral infection during pregnancy and on neonatal outcomes remains an important clinical consideration. While both structural and non-structural proteins of CVA6 are known to contribute to viral virulence, the underlying pathogenic mechanisms are not fully understood. Continuous evolution of CVA6 through genetic variation and frequent recombination has led to the emergence of distinct lineages and recombinants, posing substantial challenges to the development of effective antivirals and vaccines. To address these gaps, this review systematically examines the global epidemiology, pathogenic mechanisms, evolutionary dynamics, current diagnostic tools, and antiviral strategies for CVA6. By integrating these perspectives, this work aims to inform public health preparedness and guide future research toward mitigating outbreaks driven by emerging recombinants and novel enterovirus serotypes.
Humans↗
Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.
The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n = 6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-β-CoV vaccines.
Animals↗
Cancer and environment.
The attention of scientists has been directed mostly to analyze the influence of the environment on tumor induction. However, the external environment can also enhance the reactivity of the host organism towards tumors, by activating several immune mechanisms. Moreover, the host organism is the first "foreign" environment with which tumor cells come into contact in a dynamic way, characterized by a continuous evolution.
Animals↗
[Technology and real performances of a new circuit for new pacemaker (author's transl)].
Continuing evolution in cardiac stimulation today imposes on PM manufacturers the need to submit their products under new criteria, such as: contained dimensions, functional complexity and longer periods of patient care. PM electronic circuity plays a determinant role in meeting the best solution of these problems. Thick film hybrid technology has been chosen by the Authors because it is deemed to be the best compromise for the present goals, such as: low power consumption, low weight and small size, electrical parameters stability, functional complexity and high circuitry density, Hi-Rel performance for longer working life. A little space has been reserved for schematic diagrams of the manufacturing cycle and the applied technology; particular evidence has been shown concerning selection criteria for circuitry component selection and Hi-Rel tests for the end product. Hi-Rel and qualification standards have been selected by the Authors from MIL-STD 883 methods and AAMI-FDA pacemakers standards. Practical results of the application of this methodology can be summarised as follows: only 44-50% of the total circuits pass the complete cycle of tests and thus are used for PM manufacture; electronic failure rate in the implanted units is 0.024% failure per month.
Electronics↗
Validity of the Ann Arbor staging classification for the non-Hodgkin's lymphomas.
The Ann Arbor staging classification has proved to be valuable for Hodgkin's disease. When proposed in 1971 it was thought that it could also be applied to the non-Hodgkin's lymphomas. The diversity of the non-Hodgkin's groups, the continued evolution of histopathologic classifications, and the great frequency of advanced disease in the lymphocytic subgroups make the Ann Arbor classification of only limited value for the non-Hodgkin's lymphomas.
Bone Marrow↗
An Orthogonal T7 Replisome for Continuous Hypermutation and Accelerated Evolution in E. coli.
Systems that perform continuous hypermutation of designated genes without compromising the integrity of the host genome can dramatically accelerate the evolution of new or enhanced protein functions. We describe an orthogonal DNA replication system in E. coli based on the controlled expression of the replisome of bacteriophage T7. The system replicates circular plasmids that enable high transformation efficiencies and seamless integration into standard molecular biology workflows. Engineering of T7 DNA polymerase yielded variant proteins with mutation rates of 1.7 × 10 -5 substitutions per base in vivo - 100,000-fold above the genomic mutation rate. Continuous evolution using the mutagenic T7 replisome was demonstrated by expanding the substrate scope of TEM-1 β-lactamase and increase activity 1,000-fold against clinically relevant monobactam and cephalosporin antibiotics in less than one week.
Journal Article↗
An orthogonal T7 replisome for continuous hypermutation and accelerated evolution in E. coli.
Systems that perform continuous hypermutation of designated genes without compromising the integrity of the host genome can substantially accelerate the evolution of new or enhanced protein functions. We describe an orthogonal DNA replication system in Escherichia coli based on the controlled expression of the replisome of bacteriophage T7 (T7-ORACLE). The system replicates circular plasmids that enable high transformation efficiencies and seamless integration into standard molecular biology workflows. Engineering of T7 DNA polymerase yielded variant proteins with mutation rates of 1.7 × 10-5 substitutions per base in vivo-100,000-fold above the genomic mutation rate. We demonstrated continuous evolution using the T7 replisome by expanding the substrate scope of TEM-1 β-lactamase and increasing activity 5000-fold against clinically relevant monobactam and cephalosporin antibiotics in less than 1 week.
Bacteriophage T7↗
Phylogeny and evolution of SARS-CoV-2 during Delta and Omicron variant waves in India.
SARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was reported in patients without comorbidity (97%), while Omicron BA.2 was reported in patients with comorbidity (77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2. Higher propensity of Omicron variants to bronchial tissue, probably ensured increased transmission while Omicron BA.2 became the prevalent variant possibly due to evolutionary trade-off. Virus evolution continues to shape the epidemic and its culmination.Communicated by Ramaswamy H. Sarma.
SARS-CoV-2↗