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PubMed2026

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↗
PubMed1976

Introducing quality assurance and medical audit into the UCSF medical center curriculum.

The experience gained by a medical school faculty in developing and piloting a course for undergraduate medical students in medical care evaluation led to a similar effort for house staff. It is recognized that if the profession is to fulfill the demand by society for social accountability in the use of resources for health care, medical care assessment and quality assurance mechanisms must become an intimate part of the clinical experience of medical students and house officers. Teaching these subjects requires a theoretical framework; introduction of content and skills appropriate to the level of the student and continuation of progressively more advanced training throughout medical education; use of assessment and quality assurance techniques by clinician-teachers themselves to provide models for the student; and continued evolution of pedagogic approach and course content based on developments in the area.

California↗
PubMed1977

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↗
PubMed1992

On the evolution of language and generativity.

One of the properties that most conspicuously distinguishes human language from any other form of animal communication is generativity. Language with this property therefore presumably evolved with the Homo line somewhere between H. habilis and H. sapiens sapiens. Some have suggested that it emerged relatively suddenly and completely with H. sapiens sapiens, and this view is consistent with (a) linguistic estimates as to when vocal language emerged, (b) the relatively late "explosion" of manufacture and cultural artifacts such as body ornamentation and cave drawings, and (c) evidence on changes in the vocal apparatus. However, evidence on brain size and developmental patterns of growth suggests an earlier origin and a more continuous evolution. I propose that these scenarios can be reconciled if it is supposed that generative language evolved, perhaps from H. habilis on, as a system of manual gestures, but switched to a predominantly vocal system with H. sapiens sapiens. The subsequent "cultural explosion" can then be attributed to the freeing of the hands from primary involvement in language, so that they could be exploited, along with generativity, for manufacture, art, and other activities.

Brain↗
PubMed2026

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↗
PubMed1992

A randomized controlled trial of early surgery in Duchenne muscular dystrophy.

We performed a randomized controlled trial of early surgical treatment of contractures in 20 boys with Duchenne muscular dystrophy, age 4-6 yr. Surgery consisted of release of hip flexors, removal of iliotibial bands, and lengthening of tendo Achilles bilaterally. All patients were monitored for at least 12 months post-randomization, and assessed quantitatively for muscle strength and function. Surgery corrected the deformities, but had no beneficial effect on strength or function. Indeed, data in the second year showed more rapid deterioration of function in some of the operated boys. There appeared to be continued evolution of pathology following surgery, as assessed by sequential muscle ultrasound and muscle biopsy. We cannot recommend this type of surgery as a routine treatment.

Biopsy↗
PubMed1978

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↗
PubMed2026

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↗
PubMed1992

A continuous spectrum of hypercoagulability exists in acute nonlymphoblastic leukemia.

A consumption coagulopathy syndrome has frequently been reported in association with some cases of acute nonlymphoblastic leukemia (ANLL) and mainly in acute promyelocytic leukemia (M3). Eighteen cases of ANLL have been studied on admission, before chemotherapy was started. Levels of antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (T-AT-III), tissue plasminogen activator, plasminogen (Pg), alpha-2-antiplasmin (alpha-2-AP), D-dimer (DD) and fibrinogen (Fg) were determined. The results showed normal levels of AT-III and PS, decreased levels of PC, alpha-2-AP, Pg and Fg in some cases, and an elevation of DD and T-AT III complex in almost all patients. There was a continuous evolution of data from M1 cases in which only slight alterations were seen up to M3 cases where all those pathologic data were observed.

Adult↗
PubMed2025

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↗
PubMed1992

The computer-based medical record: current status.

At the turn of the century, neither hospitals nor physicians routinely kept clinical records. Since then, the medical record has gradually evolved. More recently, as society and medicine have become more complex and sophisticated, inadequacies of the paper medical record have become increasingly apparent. The computer-based medical record addresses many of the deficiencies of the paper record. Meanwhile, barriers to computer-based records have decreased; hardware has become more affordable, powerful, and compact, and software has been refined. Socially, the major payers for health care are demanding verification of the effectiveness and quality of care, information that involves data-intensive research. The electronic medical record promises to improve quality of care by providing point-of-care reminder and decision support tools as well as a database for substantiating the effectiveness of care. In conjunction with the growing integration of computers into all facets of life, government agencies, computer giants, and medical organizations are currently laying the groundwork for the development of standardized elements and formats for computer-based medical information systems. As part of the continuing evolution of the medical record, we foresee these forces culminating in the computerization of the clinical record. In this review, we briefly describe the developments that led us to this conclusion and describe computer-based clinical record systems in use in two family practice settings.

Decision Support Techniques↗
PubMed1992

The Science of Unitary Human Beings: a contemporary literature review.

This literature review identifies the origins of the Science of Unitary Beings, explores definitions of the main components of the conceptual framework and highlights the latest developments in its continual evolution. Examples of how nurse researchers and practitioners have interpreted these components and latest developments are given. The author shows that rather than being an obscure and esoteric framework, the Science of Unitary Human Beings has already had a considerable influence on nursing practice, education and research in North America. A prediction is made that in years to come the framework may begin to have the same impact in the United Kingdom.

Humans↗
PubMedDate not supplied

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↗
PubMed1978

[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↗
PubMed1977

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↗
PubMed2024

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↗
PubMed2025

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↗