Revolutionizing Digital Pathology With the Power of Generative Artificial Intelligence and Foundation Models.

Digital pathology has transformed the traditional pathology practice of analyzing tissue under a microscope into a computer vision workflow. Whole-slide imaging allows pathologists to view and analyze microscopic images on a computer monitor, enabling computational pathology. By leveraging artificial intelligence (AI) and machine learning (ML), computational pathology has emerged as a promising field in recent years. Recently, task-specific AI/ML (eg, convolutional neural networks) has risen to the forefront, achieving above-human performance in many image-processing and computer vision tasks. The performance of task-specific AI/ML models depends on the availability of many annotated training datasets, which presents a rate-limiting factor for AI/ML development in pathology. Task-specific AI/ML models cannot benefit from multimodal data and lack generalization, eg, the AI models often struggle to generalize to new datasets or unseen variations in image acquisition, staining techniques, or tissue types. The 2020s are witnessing the rise of foundation models and generative AI. A foundation model is a large AI model trained using sizable data, which is later adapted (or fine-tuned) to perform different tasks using a modest amount of task-specific annotated data. These AI models provide in-context learning, can self-correct mistakes, and promptly adjust to user feedback. In this review, we provide a brief overview of recent advances in computational pathology enabled by task-specific AI, their challenges and limitations, and then introduce various foundation models. We propose to create a pathology-specific generative AI based on multimodal foundation models and present its potentially transformative role in digital pathology. We describe different use cases, delineating how it could serve as an expert companion of pathologists and help them efficiently and objectively perform routine laboratory tasks, including quantifying image analysis, generating pathology reports, diagnosis, and prognosis. We also outline the potential role that foundation models and generative AI can play in standardizing the pathology laboratory workflow, education, and training.

Eigenvalue based spectral classification.

This paper describes a new method of classification based on spectral analysis. The motivations behind developing the new model were the failures of the classical spectral cluster analysis based on combinatorial and normalized Laplacian for a set of real-world datasets of textual documents. Reasons of the failures are analysed. While the known methods are all based on usage of eigenvectors of graph Laplacians, a new classification method based on eigenvalues of graph Laplacians is proposed and studied.

The Algorithm of Determining an Anti-Collision Manoeuvre Trajectory Based on the Interpolation of Ship's State Vector.

The determination of a ship's safe trajectory in collision situations at sea is one of the basic functions in autonomous navigation of ships. While planning a collision avoiding manoeuvre in open waters, the navigator has to take into account the ships manoeuvrability and hydrometeorological conditions. To this end, the ship's state vector is predicted-position coordinates, speed, heading, and other movement parameters-at fixed time intervals for different steering scenarios. One possible way to solve this problem is a method using the interpolation of the ship's state vector based on the data from measurements conducted during the sea trials of the ship. This article presents the interpolating function within any convex quadrilateral with the nodes being its vertices. The proposed function interpolates the parameters of the ship's state vector for the specified point of a plane, where the values in the interpolation nodes are data obtained from measurements performed during a series of turning circle tests, conducted for different starting conditions and various rudder settings. The proposed method of interpolation was used in the process of determining the anti-collision manoeuvre trajectory. The mechanism is based on the principles of a modified Dijkstra algorithm, in which the graph takes the form of a regular network of points. The transition between the graph vertices depends on the safe passing level of other objects and the degree of departure from the planned route. The determined shortest path between the starting vertex and the target vertex is the optimal solution for the discrete space of solutions. The algorithm for determining the trajectory of the anti-collision manoeuvre was implemented in autonomous sea-going vessel technology. This article presents the results of laboratory tests and tests conducted under quasi-real conditions using physical ship models. The experiments confirmed the effective operation of the developed algorithm of the determination of the anti-collision manoeuvre trajectory in the technological framework of autonomous ship navigation.

The Influence of Mechanical Alloying and Plastic Consolidation on the Resistance to Arc Erosion of the Ag-Re Composite Contact Material.

The article presents the influence of mechanical alloying and plastic consolidation on the resistance to arc erosion of the composite Ag-Re material against the selected contact materials. The following composites were selected for the tests: Ag90Re10, Ag95Re5, Ag99Re1 (bulk chemical composition). Ag-Re materials were made using two methods. In the first, the materials were obtained by mixing powders, pressing, sintering, extrusion, drawing, and die forging, whereas, in the second, the process of mechanical alloying was additionally used. The widely available Ag(SnO2)10 and AgNi10 contact materials were used as reference materials. The reference AgNi10 material was made by powder metallurgy in the process of mixing, pressing, sintering, extrusion, drawing, and die forging, while the Ag(SnO2)10 composite was obtained by spraying AgSniBi alloy with water, and then the powder was pressed, oxidized internally, sintered, extruded into wire, and drawn and die forged. The tests of electric arc resistance were carried out for loads with direct current (DC) and alternating current (AC). For alternating current (I = 60 A, U = 230 V), 15,000 switching cycles were made, while, for constant current 50,000 (I = 10 A, U = 550 V). A positive effect of the mechanical alloying process and the addition of a small amount of rhenium (1% by mass) on the spark erosion properties of the Ag-Re contact material was found. When DC current of 10 A was used, AgRe1 composite was found to be more resistant than commonly used contact materials (AgNi10 and Ag(SnO2)10).

First Report of Echinococcus ortleppi in Human Cases of Cystic Echinococcosis in Poland.

Cystic echinococcosis is considered as an emerging zoonosis that can develop asymptomatically for years, clinically nonpathognomic. The disease is of public health importance due to often late, difficult diagnostics, uncertain results of treatment, the need to remove hydatid cysts surgically in advanced cases, and poor prognosis in untreated patients. Six Polish female patients with diagnosed cystic echinococcosis (CE) were examined. DNA extracted from the liver and lung samples served for amplification of mitochondrial nad1 gene fragment. Sequence alignments of 5 isolates showed identity with the pig strain, Echinococcus canadensis G7. One case was in 100% identical with Echinococcus ortleppi G5, the cattle strain. These data demonstrate first report of E. ortleppi, regarded as extinct species, causing human cystic echinococcosis in Poland, where the most frequent causative agent of human CE is E. canadensis.

A Retrospective Observational Study of Uveitis in a Single Center in Poland with a Review of Findings in Europe.

BACKGROUND This study aimed to review the causes, presentation, and clinicopathological associations of uveitis in a single department of ophthalmology in Poland, and to compare the findings with previously published studies from other European countries. MATERIAL AND METHODS Review of local patient records between 2005-2015 identified patients diagnosed with uveitis. Data obtained included age, gender, imaging findings, and laboratory diagnostic findings. A literature review identified 24 publications from 1976-2017 that reported observational data from patients with uveitis in Europe. Statistical analysis compared the findings. RESULTS Between 2005-2015, 279 patients were diagnosed with uveitis (mean age, 38.3±15.3 years) (61.6% women) including unilateral uveitis (60.5%), with posterior uveitis (48.4%), anterior uveitis (26.5%), and intermediate uveitis (12.9%). A general etiology was established in 76.3% and included ocular-specific syndromes (31.8%), infection (27.9%), and an association with systemic disease (16.8%), but 23.6% were unclassifiable. Specific causes of uveitis included toxoplasmosis (17.9%), Fuchs uveitis (12.2%), white dot syndromes (WDS) (10.4%), sarcoidosis (6.1%), toxocariasis (6.1%), HLA-B27-associated acute anterior uveitis (AAU) (5.7%), multiple sclerosis (4.7%), ankylosing spondylitis (3.6%) and herpesvirus infection (2.5%). Data from 26 published studies (24,126 patients with uveitis) from 12 European countries showed that idiopathic uveitis was most common (36.6%); the identified causes included toxoplasmosis (9.4%), WDS (7.2%), and Fuchs uveitis (6.1%). CONCLUSIONS In a single ophthalmic center in Poland, and throughout Europe, the causes of uveitis are varied. Genetic, geographic, social and environmental factors are likely to affect the cause of uveitis in different populations.

Adverse Reactions in Antifolate-Treated Toxoplasmic Retinochoroiditis.

This study seeks to define factors affecting the development of adverse reactions to intensive therapy of toxoplasmic retinochoroiditis with antifolate agents (pyrimethamine/sulfadoxine) and antibiotics followed by secondary antifolate prophylaxis. The study was of retrospective and observational nature. Medical files were reviewed of 551 patients suffering from ocular toxoplasmosis during 1994-2013. All patients were treated with the same protocol: 3-week intensive pyrimethamine/sulfadoxine plus antibiotic/steroid therapy. Three hundred and fourteen out of the 551 patients qualified for the subsequent 6-month long secondary antifolate prophylaxis. The type and occurrence rate of adverse reactions were taken into account. The probability of an adverse reaction during the intensive therapy phase was 33.4%. Hypertransaminasemia was the most common event observed in 24.6% of the patients, but it assumed a severe character in just 0.9%, with male gender and age over 25 years being the predisposing factors. Less common adverse effects included thrombocytopenia (8.3%), hypersensitivity skin reactions (3.0%), and abdominal pain (1.4%). The adverse effects of secondary antifolate prophylaxis, most commonly hypersensitivity skin reactions and hypertransaminasemia, followed by thrombocytopenia and abdominal pain, were observed in 4.9% of the patients. Ten of them (2.7%) had to discontinue the treatment while eight others continued with pyrimethamine alone without further adverse effects, which suggests that discontinuation of the sulfonamide decreased the propensity for adverse reactions. The treatment strategy in these patients differed from previous reports in that it used lower doses of pyrimethamine/sulfonamide, with no folinic acid supplementation. Nonetheless, the rate and severity of adverse events were no greater than those noticed with traditional regimens, with higher antifolate doses and folinic acid supplementation. We conclude that the dose and drug-mitigated treatment strategy we employed deserves consideration as a promising alternative to traditional treatments for ocular toxoplasmosis.

Molecular determination of suspected alveolar echinococcosis requiring surgical treatment in human cases from Poland

In this study five cases of suspected alveolar echinococcosis from Poland in which surgical treatment was needed, previously diagnosed by means of imaging and serological techniques, were analyzed in terms to identify the causative agent. Samples of the parasite tissues taken perioperatively from the liver lesions were used for the histopathological and molecular examinations. The sequences of all isolates were identical to Echinococcus multilocularis; all nad1 sequences have been deposited in GenBank The histopathological examination revealed Passpositive fragments of laminated layers typical for E. multilocularis metacestode. Obtained results confirm that the use of imaging techniques only may be insufficient to diagnose alveococcosis thus the recognition of the zoonosis should base on several procedures; especially valuable are highly sensitive and specific molecular methods.

Cerebellar liponeurocytoma with atypical histological features - a rare example of a glioneuronal tumor.

We present a case of a rare neoplasm in a 77-year-old woman with previous oncological history, who developed a rapid onset of cerebellar symptoms. The neuroimaging detected a posterior fossa tumor suspected of meningioma which was completely resected soon after. Histologically the neoplasm had two components with different immunophenotype. One constituent was lobular, composed of monotonous mitotically active round cells with a predominant neuronal profile. The second, astrocytic component contained lipomatous cells intermixed with larger gemistocytic astrocytes. Fields of geographic necrosis as well as multifocal microvascular proliferation were observed. The Ki67 proliferation index was 12%. After two years of follow-up the patient remains free of symptoms and radiologic recurrence. The presented case of cerebellar liponeurocytoma is unusual in terms of its atypical histological features and prominent astrocytic component. The authors propose that the term 'lipomatous glioneuronal tumor' seems to be more appropriate for this type of lesion, considering its histologic spectrum and possible extracerebellar location.

The Ship Movement Trajectory Prediction Algorithm Using Navigational Data Fusion.

It is essential for the marine navigator conducting maneuvers of his ship at sea to know future positions of himself and target ships in a specific time span to effectively solve collision situations. This article presents an algorithm of ship movement trajectory prediction, which, through data fusion, takes into account measurements of the ship's current position from a number of doubled autonomous devices. This increases the reliability and accuracy of prediction. The algorithm has been implemented in NAVDEC, a navigation decision support system and practically used on board ships.

Seroprevalence of Bartonella Species in Patients with Ocular Inflammation.

Bartonella species, vector-borne etiologic agents of many systemic or self-limited infections, are responsible for a widening spectrum of diseases in humans, including inflammatory conditions of the eye. The aim of this study was to determine whether there is any relationship between uveitis and the evidence of Bartonella spp. infection in the serum, ocular fluid, and cataract mass in patients with intraocular inflammation. Polymerase chain reaction (PCR)-based tests and DNA sequencing were performed on surgery-extracted specimens of intraocular fluid and lens mass of 33 patients. Sera from 51 patients and 101 control subjects were tested for the presence of specific antibodies against Bartonella spp. Neither IgM-class antibodies against Bartonella spp. nor Bartonella spp. DNA were detected. A specific IgG-class antibody was found in 33.3% of the patients with uveitis. The rate of positive Bartonella serology was higher among the uveitis patients than that in control subjects. This high rate may in part result from unrecognized indirect mechanisms rather than the immediate presence and multiplication of Bartonella spp. in the eyeball. Nonetheless we believe that screening for Bartonella spp. should become part of the diagnostic workup in uveitis.

Observation and Clinical Pattern in Patients with White Dot Syndromes: The Role of Color Photography in Monitoring Ocular Changes in Long-Term Observation.

BACKGROUND The aim of this study was to assess the clinical course and distinctive features of different white dot syndromes (WDS) in patients attending the Ophthalmology Department, Medical University of Warsaw in the years 1995-2015. MATERIAL AND METHODS Sixty-two (62) patients (43 females and 19 males), aged 18 to 77 years, referred with a WDS were included in this prospective study, with observation period ranging from 5 months to 16 years. All patients underwent a complete ophthalmological examination and multimodal imaging studies. RESULTS In this cohort of 62 patients, the following WDS entities were identified: multifocal choroiditis with panuveitis (MFCPU), multifocal choroiditis (MFC), punctate inner choroidopathy (PIC), birdshot, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), subretinal fibrosis and uveitis, multiple evanescent white dot syndrome (MEWDS), serpiginous choroiditis, and single cases of acute annular outer retinopathy (AAOR). CONCLUSIONS The study was performed at a Polish referral center and may to some extent reflect the varied geographical distribution of white dot syndromes, as none of the subjects was found to suffer from acute zonal occult outer retinopathy (AZOOR), acute macular neuroretinopathy (AMN), or diffuse unilateral subacute neuroretinitis (DUSN). Long-term follow-up is warranted by the evolution of lesions in the eye fundus, while management depends on correct diagnosis of WDS. When the posterior pole is involved in some cases of the WDS an immunosuppressive treatment, the use of the PDT or anti-VEGF injections were necessary.

Inference Engine in an Intelligent Ship Course-Keeping System.

The article presents an original design of an expert system, whose function is to automatically stabilize ship's course. The focus is put on the inference engine, a mechanism that consists of two functional components. One is responsible for the construction of state space regions, implemented on the basis of properly processed signals recorded by sensors from the input and output of an object. The other component is responsible for generating a control decision based on the knowledge obtained in the first module. The computing experiments described herein prove the effective and correct operation of the proposed system.

The Impact of Short-Term, Intensive Antifolate Treatment (with Pyrimethamine and Sulfadoxine) and Antibiotics Followed by Long-Term, Secondary Antifolate Prophylaxis on the Rate of Toxoplasmic Retinochoroiditis Recurrence.

PURPOSE: To assess the impact of intensive antifolate treatment, followed by secondary antifolate prophylaxis (A-SP) on the recurrence rate of toxoplasmic retinochoroiditis (TRC). To investigate whether there are any other factors potentially predisposing for recurrence. MATERIAL AND METHODS: A total of 637 medical records of TRC patients, who had been treated in the years 1994-2013 were reviewed. All patients were treated with pyrimethamine /sulfadoxine one 25mg/500mg tablet daily (P/S 25/500mg) for 21 days with a double loading dose for the first two days. From Day 2 the patients also received prednisone at a starting dose of 40mg and spiramycine 3 million IU three times daily, given for 10 days followed by azithromycin 500mg once daily for another 6 days. The analysis of the recurrence rate involved 352 patients who had completed 6-month secondary prophylaxis (P/S one 25 mg/500mg tablet twice a week). RESULTS: When secondary antifolate prophylaxis (A-SP) was instituted immediately after the treatment for TRC, the probability of 3-year recurrence-free survival after the first course of A-SP was 90.9%. A recurrence was most likely approximately 3.5 years after the first treatment. A univariate Cox regression model demonstrated that a risk for recurrence was 2.82 times higher (p = 0.02) in patients with retinal scars. In the multivariate analysis, the risk for recurrence was 2.41 higher (p = 0.06). In patients with haemorrhagic lesions the risk for recurrence was lower, aRR = 0.17 (approaching borderline statistical significance p = 0.08). CONCLUSIONS: With the institution of A-SP of immediately after the intensive treatment for TRC, i.e. when a reactivation was most likely, there was no recurrence during A-SP. Following A-SP the recurrence rates were low and recurrence-free periods tended to be longer. The treatment regimen employed had a beneficial effect on the recurrence interval as it reduced and delayed the highest probability of recurrence.

Unilateral optic disc oedema as a first sign of ocular toxoplasmosis ­ case report. / Jednostronny obrzek tarczy nerwu wzrokowego jako pierwszy objaw toksoplazmozy ocznej ­ analiza przypadku.

Diagnostic procedure for unilateral optic disc oedema needs detailed medical history, careful physical examination and multiple additional tests. We present a very rare case of atypical unilateral anterior optic neuropathy as a sign of ocular toxoplasmosis in a young female. All diagnostic and therapeutic challenges have been discussed.

Cases of Echinococcus granulosus Sensu Stricto Isolated from Polish Patients: Imported or Indigenous?

The cases of nine Polish patients with diagnosed cystic echinococcosis (CE) were examined. A total of nine isolates obtained postoperatively were investigated using PCR and sequencing. The mitochondrial region of nad1 gene was amplified. This PCR and sequencing analysis revealed the presence of Echinococcus canadensis G7 in seven patients and E. granulosus G1 in two patients. These data demonstrate that E. canadensis is the predominant causative agent of human cystic echinococcosis in Poland. E. granulosus G1 detection in Polish patients suggests that the parasite was imported; however it does not exclude the possibility that these cases could have been of Polish origin.

Do pregnancy, postpartum period and lactation predispose to recurrent toxoplasmic retinochoroiditis?

BACKGROUND: The aim of the study was a statistical analysis of the possible effects of pregnancy, postpartum period, and lactation on increased risk for reactivation of toxoplasmic retinochoroiditis. MATERIAL AND METHODS: A retrospective study was undertaken of the clinical records of 661 patients referred with the diagnosis of acute toxoplasmic retinochoroiditis to the Department of Zoonoses and Tropical Diseases, Medical University of Warsaw and to the Department of Ophthalmology, Medical University of Warsaw in the years 1994-2014. This group of inpatients consisted of 213 women of child-bearing age (18 to 40 years). Reactivation of toxoplasmic retinochoroiditis was observed in 24 women aged 15 to 39 years who were pregnant, in the postpartum period, or lactating. To compare the rate of the relapses in pregnant/lactating patients vs. non-pregnant/non-lactating patients, the Fisher exact test was used. Calculations were performed with WinPepi software (Abramson JH (2004) WINPEPI (PEPI-for-Windows) for epidemiologists. Epidemiologic Perspectives & Innovations, 2005, 1: 6). RESULTS: A total of 28 reactivations of toxoplasmic retinochoroiditis were observed (16 episodes in pregnancy, 4 in the postpartum period, and 8 during lactation) in 24 women aged 15 to 39 years. In 3 women, multiple episodes were reported (in early pregnancy and the postpartum period in 2 women, and during 2 pregnancies and lactation in 1 woman). Statistical analysis showed that the risk of an episode of toxoplasmic retinochoroiditis is 7.4-fold higher in pregnancy compared to the non-pregnant/non-lactating women (p<0.0001). CONCLUSIONS: Women of childbearing age with toxoplasma ocular lesions should be informed by their doctors about possible active recurrences during pregnancy and should be followed carefully by an ophthalmologist when pregnant.

Management of toxoplasmic retinochoroiditis during pregnancy, postpartum period and lactation: clinical observations.

BACKGROUND: During pregnancy and labor, the immune response is physiologically impaired and women are more susceptible to infections. Since many drugs may have potentially adverse effects on the fetus and newborn, less aggressive treatment regimens should be considered in pregnant and lactating patients. The aim of our study was to present the management of toxoplasmic retinochoroiditis during pregnancy, postpartum period, and lactation. MATERIAL AND METHODS: A retrospective study was undertaken of the clinical records of 24 women during pregnancy, postpartum period, and lactation who were referred in the years 1994-2014 to the Department of Zoonoses and Tropical Diseases or the Department of Ophthalmology, Medical University of Warsaw for toxoplasmic retinochoroiditis. The diagnosis was based on the typical ophthalmoscopic picture, confirmed by serological testing using an ELISA method. RESULTS: A total of 28 attacks of toxoplasmic retinochoroiditis were observed in 24 patients during pregnancy, postpartum period, and lactation. The choice of treatment was guided by the character and location of the inflammatory lesion and the gestational age. Topical (steroidal/nonsteroidal eye drops) and systemic treatments with spiramycin or azithromycin, Fansidar (pyrimethamine 25 mg/sulfadoxine 500 mg), and prednisone were used. CONCLUSIONS: Management of toxoplasmic retinochoroiditis during pregnancy, postpartum period, or lactation must be individualized and guided by the gestational age and location of the active lesion. Women of childbearing age with toxoplasma ocular lesions should be informed by their doctors about possible active recurrences during pregnancy and followed carefully by an ophthalmologist when pregnant.

The first case of human autochtonous subconjunctival dirofilariosis in Poland and MALT lymphoma as possible consequence of this parasitosis.

The first case of human dirofilarosis in Poland was recorded in 2007. Until that time our country was free of Dirofilaria repens. Recent studies show that 21,4- 60% of dogs in Warsaw region harbour microfilariae, therefore it is becoming a growing problem in Central Europe. In April 2013 a subconjunctival D. repens was removed from the eye of 61-year-old woman. It was the twenty first case of this disease in Poland, the third case of eye dirofilaria and the fourth autochtonous case. The patient had never been abroad, so it was the first case of autochtonous human ocular dirofilariosis in Poland. Nine months after the D. repens had been removed, a MALT lymphoma was discovered. In the article we discuss whether a MALT lymphoma of the lacrimal gland of the eye, previously affected by the parasite, may be the consequence of the invasion.

[Atypical case of acute retinal necrosis secondary to the primary herpes simplex infection]. / Nietypowy przypadek ostrej martwicy siatkówki w przebiegu pierwotnego zakazenia wirusem herpes simplex.

Acute retinal necrosis is a rare manifestation of viral chorioretinitis, accompanied by occlusive vasculitis, which is associated with poor visual prognosis. The main causal factors include varicella-zoster virus in older patients and herpes simplex in younger ones. The disease typically manifests as a reactivation of latent infections. We present a case of a 57-year-old female with atypical clinical manifestation of acute retinal necrosis secondary to the primary viral infection with herpes simplex. The serology panel of vitreous tap and blood sample confirmed viral aetiology (H. simplex). The initial clinical signs included optic disc edema with retinitis presenting as self-limiting, slowly progressing, peripheral lesions, later followed by uveitis. The antiviral therapy resolved the symptoms of uveitis and enabled healing of retinal lesions, however the natural course of disease was later complicated with retinal detachment. It was successfully treated with vitreoretinal surgery. Despite aggressive treatment, the final visual outcome was unfavourable, due to optic nerve atrophy.