A foundation model for clinical-grade computational pathology and rare cancers detection.

The analysis of histopathology images with artificial intelligence aims to enable clinical decision support systems and precision medicine. The success of such applications depends on the ability to model the diverse patterns observed in pathology images. To this end, we present Virchow, the largest foundation model for computational pathology to date.

Clinical Validation of Artificial Intelligence-Augmented Pathology Diagnosis Demonstrates Significant Gains in Diagnostic Accuracy in Prostate Cancer Detection.

Context.—: Prostate cancer diagnosis rests on accurate assessment of tissue by a pathologist. The application of artificial intelligence (AI) to digitized whole slide images (WSIs) can aid pathologists in cancer diagnosis, but robust, diverse evidence in a simulated clinical setting is lacking.

Independent real-world application of a clinical-grade automated prostate cancer detection system.

Artificial intelligence (AI)-based systems applied to histopathology whole-slide images have the potential to improve patient care through mitigation of challenges posed by diagnostic variability, histopathology caseload, and shortage of pathologists. We sought to define the performance of an AI-based automated prostate cancer detection system, Paige Prostate, when applied to independent real-world data. The algorithm was employed to classify slides into two categories: benign (no further review needed) or suspicious (additional histologic and/or immunohistochemical analysis required).

Mucosal IgA responses in healthy adult volunteers following intranasal spray delivery of a live attenuated measles vaccine.

Measles remains an important cause of morbidity and mortality among children in the developing world. The goal of this study was to examine measles virus-specific mucosal immune responses in healthy immune (n = 24; plaque reduction neutralization [PRN] titers of ≥200 mIU/ml) and nonimmune (n = 24) young adult volunteers who received the monovalent Moraten measles vaccine via intranasal (spray delivery) or subcutaneous immunization. Serum, oral fluid, and nasal wash samples were examined for measles virus-specific and total IgG and IgA on day 0 (prior to vaccination) and on days 14, 28, and 90 after vaccination.

Topological approach of Jungian psychology.

In this work, we compare two global approaches which are usually considered as completely unconnected one with the other. The former is Thom's topology and the latter is Jung's psychology. More precisely, it seemed to us interesting to adapt some morphologies of Thom's catastrophe theory to some Jung's notions.

New strategies to overcome the drawbacks of currently available flu vaccines.

Vaccination represents the most efficient tool to control morbidity and mortality resulting from influenza infections in humans. The currently licensed influenza vaccines provide good protection levels in healthy adults, whereas lower protection is generally achieved in ageing individuals who are at a higher risk of developing severe clinical manifestations. Future improvements in influenza vaccines should address the needs of high risk groups including the elderly, small children and chronic patients.

Assessment by electron-microscopy of recombinant Vibrio cholerae and Salmonella vaccine strains expressing enterotoxigenic Escherichia coli-specific surface antigens.

Diarrhoea caused by enterotoxigenic Escherichia coli (ETEC) requires adhesion of microorganisms to enterocytes. Hence, a promising approach to immunoprophylaxis is to elicit antibodies against colonisation factor antigens (CFAs). Genes encoding the most prevalent ETEC-specific surface antigens were cloned into Vibrio cholerae and Salmonella vaccine strains.

Morphological and immunocytochemical analysis of Escherichia coli-specific surface antigens in wildtype strains and in recombinant Vibrio cholerae.

Adhesion is the first step in the pathogenesis of enterotoxigenic Escherichia coli infections. The genes encoding the most prevalent adhesion factors CFA/I, CS3 and CS6 were cloned into Vibrio cholerae strain CVD 103-HgR and expression of fimbriae was investigated in wildtype and recombinant strains by transmission electron microscopy in conjunction with immunolabelling and negative staining. Negative staining was effective in revealing CFA/I and CS3, but not CS6.

A clinical study to assess the safety and immunogenicity of attenuated measles vaccine administered intranasally to healthy adults.

Background: Despite the availability of a safe and effective vaccine for over four decades, measles remains one of the most common infectious disease killers of children in the world. Mucosal administration of currently licensed measles vaccine has been proposed to address issues of needle safety and improve vaccine uptake.

Methods: Healthy adult volunteers were randomized to receive live-attenuated monovalent measles virus vaccine (Moraten Berna) via the standard subcutaneous (SQ) or the experimental intranasal (IN) route in a randomized, double-masked fashion.

Attenuated measles virus as a vaccine vector.

Live attenuated measles virus (MV) vaccines have an impressive record of safety, efficacy and ability to induce life-long immunity against measles infection. Using reverse genetics technology, such negative-strand RNA viruses can now be rescued from cloned DNA. This technology allows the insertion of exogenous genes encoding foreign antigens into the MV genome in such a way that they can be expressed by the MV vaccine strain, without affecting virus structure, propagation and cell targeting.

Viral vectors for malaria vaccine development.

A workshop on viral vectors for malaria vaccine development, organized by the PATH Malaria Vaccine Initiative, was held in Bethesda, MD on October 20, 2005. Recent advancements in viral-vectored malaria vaccine development and emerging vector technologies were presented and discussed. Classic viral vectors such as poxvirus, adenovirus and alphavirus vectors have been successfully used to deliver malaria antigens.

Generalised biological function.

A physiological function can be described as a cycle based on a cusp bifurcation set in catastrophe theory. This cycle involves four phases that are successively developed along a functional potential, which is used to perform a given physiological act. The work we present is firstly based on a detailed study of the global function of vision, which covers a vast field extending from the molecular to cerebral scale.

Expression of enterotoxigenic Escherichia coli colonization factors in Vibrio cholerae.

As a first step towards a vaccine against diarrhoeal disease caused by enterotoxigenic Escherichia coli (ETEC), we have studied the expression of several ETEC antigens in the live attenuated Vibrio cholerae vaccine strain CVD 103-HgR. Colonization factors (CF) CFA/I, CS3, and CS6 were expressed at the surface of V. cholerae CVD 103-HgR.

Biosafety evaluation of recombinant live oral bacterial vaccines in the context of European regulation.

Live bacterial vaccines represent a highly valid preventive strategy in the fight against infectious disease. However, the road from research to market is peppered with hurdles, one of which is the requirement for high biosafety characteristics, which the candidate vaccine has to display. In Europe, the European Agency for the evaluation of medicinal products (EMEA) is the relevant authority regulating the licensure of genetically engineered vaccines.

Plasmid maintenance systems suitable for GMO-based bacterial vaccines.

Live carrier-based bacterial vaccines represent a vaccine strategy that offers exceptional flexibility. Commensal or attenuated strains of pathogenic bacteria can be used as live carriers to present foreign antigens from unrelated pathogens to the immune system, with the aim of eliciting protective immune responses. As for oral immunisation, such an approach obviates the usual loss of antigen integrity observed during gastrointestinal passage and allows the delivery of a sufficient antigen dose to the mucosal immune system.

Improved immune responses to influenza vaccination in the elderly using an immunostimulant patch.

The elderly have greater morbidity and mortality due to influenza, and respond poorly to influenza vaccination compared to younger adults. This study was designed to determine if the adjuvant heat-labile enterotoxin from Escherichia coli (LT), administered as an immunostimulant (IS) patch on the skin with influenza vaccination, improves influenza immune responses in the elderly. Three weeks following vaccination, hemagglutination inhibition (HAI) responses in LT IS patch recipients showed improvement over those of elderly receiving vaccine alone, as demonstrated by significance or trends in fold rise [A/Panama (P = 0.

Liposomes and virosomes as delivery systems for antigens, nucleic acids and drugs.

Lipid-based vesicles are a very promising approach to treat diseases such as cancer, chronic infections and auto-immunity. Modern drug encapsulation methods allow efficient packing of therapeutic substances inside liposomes, thereby reducing the systemic toxicity of the drugs. Specific targeting can enhance the therapeutic effect of the drugs through their accumulation at the diseased site.

The survival attractor in the sensory functions: the example of hearing.

High noise levels may have an adverse effect on the normal cochlea function and lead to significant hearing loss. Clinically, exposure to high intensity impulse noise produces a wide range of audiometric effects which may result in long term or even irreversible symptoms. Nevertheless, there is sometimes a spontaneous rebound recovery of the auditory function.

Strong local and systemic protective immunity induced in the ferret model by an intranasal virosome-formulated influenza subunit vaccine.

The proliferation of influenza viruses causes costly, recurrent, annual epidemics. Current vaccines, mainly administered parenterally, have been shown to be suboptimal in terms of efficacy, particularly where local IgA responses are concerned. Recent investigations of virosomes as delivery systems for viral HA and NA antigens have demonstrated an improved immune response.

Biosafety aspects of the recombinant live oral Vibrio cholerae vaccine strain CVD 103-HgR.

The development of live attenuated vaccines, allowing for the safe and effective immunisation at mucosal surfaces, is a strategy of great interest for vaccinologists. The main advantage of this approach over conventional parenteral vaccines is the induction of strong mucosal immune responses, allowing targeting of the pathogen at the initial point of contact with the host. Further advantages include the ease of administration, high acceptance by vaccines, and relatively low production costs.

In vivo modification of the UDP-glucuronosyltransferase functional state in rat liver following hypophysectomy and partial or complete hormonal restoration.

The effects of growth hormone on the uridine diphosphate glucuronosyltransferase functional state, biophysical membrane parameters (order parameters and rotational correlation frequency) and the composition in phospholipids were studied in male rat hepatic microsomes. Sham-operated and hypophysectomized animals were injected with two different dosages of growth hormone, mimicking either the male or female growth hormone secretion pattern. Half the animals received thyroxine and cortisol in concentrations chosen to compensate for the lack of thyroid hormones and glucocorticoids in hypophysectomized rats.