Pixel-wise segmentation of cells in digitized Pap smear images.

A simple and cheap way to recognize cervical cancer is using light microscopic analysis of Pap smear images. Training artificial intelligence-based systems becomes possible in this domain, e.g., to follow the European recommendation to screen negative smears to reduce false negative cases. The first step for such a process is segmenting the cells. A large and manually segmented dataset is required for this task, which can be used to train deep learning-based solutions. We describe a corresponding dataset with accurate manual segmentations for the enclosed cells. Altogether, the APACS23 (Annotated PAp smear images for Cell Segmentation 2023) dataset contains about 37 000 manually segmented cells and is separated into dedicated training and test parts, which could be used for an official benchmark of scientific investigations or a grand challenge.

Annotated Pap cell images and smear slices for cell classification.

Machine learning-based systems have become instrumental in augmenting global efforts to combat cervical cancer. A burgeoning area of research focuses on leveraging artificial intelligence to enhance the cervical screening process, primarily through the exhaustive examination of Pap smears, traditionally reliant on the meticulous and labor-intensive analysis conducted by specialized experts. Despite the existence of some comprehensive and readily accessible datasets, the field is presently constrained by the limited volume of publicly available images and smears. As a remedy, our work unveils APACC (Annotated PAp cell images and smear slices for Cell Classification), a comprehensive dataset designed to bridge this gap. The APACC dataset features a remarkable array of images crucial for advancing research in this field. It comprises 103,675 annotated cell images, carefully extracted from 107 whole smears, which are further divided into 21,371 sub-regions for a more refined analysis. This dataset includes a vast number of cell images from conventional Pap smears and their specific locations on each smear, offering a valuable resource for in-depth investigation and study.

Iron(II) Complexes of P3 -Chain Ligands: Structural Diversity.

Iron(II) complexes containing ligands with a R2 P-P-PR2 unit were synthesized by metathesis reactions. With R=tBu, a mixture of two isomers is formed; in one of them, the terminal phosphorus binds to the Fe center (ylidic structure), while in the other one, the central P atom is linked to Fe. Starting from differently functionalized parent triphosphanes and corresponding functionalized Fe complexes, the ratio of isomers does not change. The outcome of the reaction and therefore the binding modes of the triphosphane ligands in the resulting compounds can be influenced by the size of the substituents. In the case of R=iPr a chelate complex is formed (both terminal P atoms are linked to the Fe center). Applying the mixed-substituted triphosphane, the ylidic structure of the resulting complex is preferred. The new compounds were characterized by NMR spectroscopy in solution and single-crystal X-ray diffraction in solid-state. The synthetic work was supported by DFT calculations.

Pathological Diagnosis, Work-Up and Reporting of Breast Cancer 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified on the basis of the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The recommendations cover non-operative, intraoperative and postoperative diagnostics, determination of prognostic and predictive markers and the content of cytology and histology reports. Furthermore, they address some specific issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, and some remarks about the future.

Hematological, Micro-Rheological, and Metabolic Changes Modulated by Local Ischemic Pre- and Post-Conditioning in Rat Limb Ischemia-Reperfusion.

In trauma and orthopedic surgery, limb ischemia-reperfusion (I/R) remains a great challenge. The effect of preventive protocols, including surgical conditioning approaches, is still controversial. We aimed to examine the effects of local ischemic pre-conditioning (PreC) and post-conditioning (PostC) on limb I/R. Anesthetized rats were randomized into sham-operated (control), I/R (120-min limb ischemia with tourniquet), PreC, or PostC groups (3 × 10-min tourniquet ischemia, 10-min reperfusion intervals). Blood samples were taken before and just after the ischemia, and on the first postoperative week for testing hematological, micro-rheological (erythrocyte deformability and aggregation), and metabolic parameters. Histological samples were also taken. Erythrocyte count, hemoglobin, and hematocrit values decreased, while after a temporary decrease, platelet count increased in I/R groups. Erythrocyte deformability impairment and aggregation enhancement were seen after ischemia, more obviously in the PreC group, and less in PostC. Blood pH decreased in all I/R groups. The elevation of creatinine and lactate concentration was the largest in PostC group. Histology did not reveal important differences. In conclusion, limb I/R caused micro-rheological impairment with hematological and metabolic changes. Ischemic pre- and post-conditioning had additive changes in various manners. Post-conditioning showed better micro-rheological effects. However, by these parameters it cannot be decided which protocol is better.

Mesoporous Aerogel Microparticles Injected into the Abdominal Cavity of Mice Accumulate in Parathymic Lymph Nodes.

Mesoporous aerogel microparticles are promising drug delivery systems. However, their in vivo biodistribution pathways and health effects are unknown. Suspensions of fluorescein-labeled silica-gelatin hybrid aerogel microparticles were injected into the peritoneum (abdominal cavity) of healthy mice in concentrations of 52 and 104 mg kg-1 in a 3-week-long acute toxicity experiment. No physiological dysfunctions were detected, and all mice were healthy. An autopsy revealed that the aerogel microparticles were not present at the site of injection in the abdominal cavity at the end of the experiment. The histological study of the liver, spleen, kidneys, thymus and lymphatic tissues showed no signs of toxicity. The localization of the aerogel microparticles in the organs was studied by fluorescence microscopy. Aerogel microparticles were not detected in any of the abdominal organs, but they were clearly visible in the cortical part of the parathymic lymph nodes, where they accumulated. The accumulation of aerogel microparticles in parathymic lymph nodes in combination with their absence in the reticuloendothelial system organs, such as the liver or spleen, suggests that the microparticles entered the lymphatic circulation. This biodistribution pathway could be exploited to design passive targeting drug delivery systems for flooding metastatic pathways of abdominal cancers that spread via the lymphatic circulation.

Inflammatory or malignant? Lessons from a cystic lateral neck lesion with a sudden onset / Gyulladás vagy daganat? Egy hirtelen jelentkezo lateralis cysticus nyaki terime tanulságai

Összefoglaló. A lateralis cysticus nyaki terimék két leggyakoribb oka a branchiogen cysta és a cysticus nyaki áttét. Az átfedo lokalizáció (a leggyakrabban a IIA nyaki régióban), a betegek életkora és az esetenként hirtelen kezdet alapján a két leggyakoribb ok differenciáldiagnózisa nagy kihívást jelenthet. Egy hirtelen fellépo fájdalmas, bal oldali nyaki duzzanattal, dysphagiával és lázzal jelentkezo 72 éves férfi esetét ismertetjük. A nyak komputertomográfiás vizsgálata egy 6 cm legnagyobb átméroju, vastag falú, többrekeszes cysticus terimét igazolt. Infektív branchiogen cysta lehetoségére gondolva az elváltozást eltávolítottuk. A szövettan azonban p16-pozitív laphámrákot igazolt. A primer tumort végül az ipsilateralis tonsilla palatina állományában sikerült azonosítani. A beteg definitív radioterápiában részesült, és 18 hónappal a diagnózis után tumormentes. A nyaki cystákon, az infektív nyaki cystákon és a cysticus metastasisokon kívül a humán papillómavírussal összefüggo szájgarati laphámrákok infektív cysticus vagy necroticus metastasisait is figyelembe kell venni a lateralis cysticus nyaki terimék differenciáldiagnózisában. Orv Hetil. 2020; 162(15): 595-600. Summary. Branchial cleft cysts and cystic neck metastases are the two most common causes of cystic lateral neck masses. Based on the overlapping location (neck level IIA), patient age at onset and the occasionally sudden onset, their differential diagnosis is challenging. We present a 72-year-old male presenting with a suddenly emerging painful, left-sided neck swelling, dysphagia and fever. Computed tomography showed a 6 cm thick-walled multicystic mass. With the suspected diagnosis of an infected branchial cleft cyst, the lesion was removed. Histology confirmed p16 positive squamous cell carcinoma. Primary tumor was identified in the ipsilateral palatine tonsil. Definive radiotherapy was performed and the patient is free of disease at the 18-month follow-up. Beyond pure and infected branchial cleft cysts and pure cystic metastases, infected cystic or necrotic metastasis of human papillomavirus associated oropharyngeal squamous cell carcinoma should be included in the differential diagnosis of cystic lateral neck lesions. Orv Hetil. 2021; 162(15): 595-600.

An intra-abdominal desmoid tumor.

Desmoid tumor is a very rare neoplasm which develops from fibroblasts. These tumors do not have the ability to metastasize, but they can cause significant morbidity and mortality by local invasion and they are prone to local recurrence. We present a case of an aggressive fibromatosis in a 28-year-old male patient with no previous medical history. The tumor was in the retroperitoneum and eventually caused perforation of the coecum. During the operation, no metastasis was found; however, local lymphadenopathy was seen. After the surgical resection, no adjuvant therapy (radio or chemotherapy) was given to the patient and on follow-up (after three years), no recurrence was observed.

[Pathological diagnosis, work-up and reporting of breast cancer. Recommendations from the 4th Breast Cancer Consensus Conference]. / Az emlorák patológiai diagnosztikája, feldolgozása és kórszövettani leletezése. Szakmai útmutatás a IV. Emlorák Konszenzus Konferencia alapján.

There have been some relevant changes in the diagnosis and treatment of breast cancer to implement the updating of the 2016 recommendations made during the 3rd national consensus conference on the disease. Following a wide interdisciplinary consultation, the present recommendations have been finalized after their public discussion at the 4th Hungarian Breast Cancer Consensus Conference. The recommendations cover non-operative, intraoperative and postoperative diagnostics, the determination of prognostic and predictive markers and the content of the cytology and histology reports. Furthermore, it touches some special issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, some relevant points about the future. The most important changes include the integration of the TNM 8th edition, the WHO classification of breast tumors 5th edition, the ASCO/CAP HER2 assessment guidelines from 2018, and the Yokohama terminology for cytology reporting; a more detailed text on tumor-infiltrating lymphocytes and size determination after neoadjuvant therapy and a broader discussion of molecular tests.

Indolepropionic Acid, a Metabolite of the Microbiome, Has Cytostatic Properties in Breast Cancer by Activating AHR and PXR Receptors and Inducing Oxidative Stress.

Oncobiotic transformation of the gut microbiome may contribute to the risk of breast cancer. Recent studies have provided evidence that the microbiome secretes cytostatic metabolites that inhibit the proliferation, movement, and metastasis formation of cancer cells. In this study, we show that indolepropionic acid (IPA), a bacterial tryptophan metabolite, has cytostatic properties. IPA selectively targeted breast cancer cells, but it had no effects on non-transformed, primary fibroblasts. In cell-based and animal experiments, we showed that IPA supplementation reduced the proportions of cancer stem cells and the proliferation, movement, and metastasis formation of cancer cells. These were achieved through inhibiting epithelial-to-mesenchymal transition, inducing oxidative and nitrosative stress, and boosting antitumor immune response. Increased oxidative/nitrosative stress was due to the IPA-mediated downregulation of nuclear factor erythroid 2-related factor 2 (NRF2), upregulation of inducible nitric oxide synthase (iNOS), and enhanced mitochondrial reactive species production. Increased oxidative/nitrosative stress led to cytostasis and reductions in cancer cell stem-ness. IPA exerted its effects through aryl hydrocarbon receptor (AHR) and pregnane X receptor (PXR) receptors. A higher expression of PXR and AHR supported better survival in human breast cancer patients, highlighting the importance of IPA-elicited pathways in cytostasis in breast cancer. Furthermore, AHR activation and PXR expression related inversely to cancer cell proliferation level and to the stage and grade of the tumor. The fecal microbiome's capacity for IPA biosynthesis was suppressed in women newly diagnosed with breast cancer, especially with stage 0. Bacterial indole biosynthesis showed correlation with lymphocyte infiltration to tumors in humans. Taken together, we found that IPA is a cytostatic bacterial metabolite, the production of which is suppressed in human breast cancer. Bacterial metabolites, among them, IPA, have a pivotal role in regulating the progression but not the initiation of the disease.

SerpinB2 is involved in cellular response upon UV irradiation.

Ultraviolet light induced pyrimidine dimer is a helix distortion DNA damage type, which recruits repair complexes. However, proteins of these complexes that take part in both DNA damage recognition and repair have been well-described, the regulation of the downstream steps of nucleotide excision repair (NER) have not been clearly clarified yet. In a high-throughput screen, we identified SerpinB2 (SPB2) as one of the most dramatically upregulated gene in keratinocytes following UV irradiation. We found that both the mRNA and the protein levels of SPB2 were increased upon UV irradiation in various cell lines. Additionally, UV damage induced translocation of SPB2 from the cytoplasm to the nucleus as well as the damage induced foci formation of it. Here we show that SPB2 co-localizes with XPB involved in the NER pathway at UV-induced repair foci. Finally, we demonstrated that UV irradiation promoted the association of SPB2 with ubiquitylated proteins. In basal cell carcinoma tumour cells, we identified changes in the subcellular localization of SPB2. Based on our results, we conclude that SPB2 protein has a novel role in UV-induced NER pathway, since it regulates the removal of the repair complex from the damaged site leading to cancerous malformation.

Metastatic Spread from Abdominal Tumor Cells to Parathymic Lymph Nodes.

Metastatic studies on rats showed that after subrenal implantation of tumor cells under the capsule of the kidney or subhepatic implantation under Glisson's capsule of the liver generated primary tumors in these organs. It was assumed that tumor cells that escaped through the disrupted peripheral blood vessels of primary tumors entered the peritoneal cavity, crossed the diaphragm, and appeared in the thoracal, primarily in the parathymic lymph nodes. This explanation did not answer the question whether distant lymph nodes were reached via the blood stream from the primary tumor or through the thoracal lymphatic vessels. In this work, we investigated the metastatic pathway in C3H/HeJ mice, after direct intraperitoneal administration of murine SCC VII cells bypassing the hematogenic spread of tumor cells. The direct pathway was also mimicked by intraperitoneal injection of Pelican Ink colloidal particles, which appeared in the parathymic lymph nodes, similarly to the tumor cells that caused metastasis in the parathymic lymph nodes and in the thymic tissue. The murine peritoneal-parathymic lymph node route indicates a general mechanism of tumor progression from the abdominal effusion. This pathway starts with the growth of abdominal tumors, continues as thoracal metastasis in parathymic lymph nodes and may proceed as mammary lymph node metastasis.

In Vivo Applicability of Neosartorya fischeri Antifungal Protein 2 (NFAP2) in Treatment of Vulvovaginal Candidiasis.

As a consequence of emerging numbers of vulvovaginitis cases caused by azole-resistant and biofilm-forming Candida species, fast and efficient treatment of this infection has become challenging. The problem is further exacerbated by the severe side effects of azoles as long-term-use medications in the recurrent form. There is therefore an increasing demand for novel and safely applicable effective antifungal therapeutic strategies. The small, cysteine-rich, and cationic antifungal proteins from filamentous ascomycetes are potential candidates, as they inhibit the growth of several Candida spp. in vitro; however, no information is available about their in vivo antifungal potency against yeasts. In the present study, we investigated the possible therapeutic application of one of their representatives in the treatment of vulvovaginal candidiasis, Neosartorya fischeri antifungal protein 2 (NFAP2). NFAP2 inhibited the growth of a fluconazole (FLC)-resistant Candida albicans strain isolated from a vulvovaginal infection, and it was effective against both planktonic cells and biofilm in vitro We observed that the fungal cell-killing activity of NFAP2 is connected to its pore-forming ability in the cell membrane. NFAP2 did not exert cytotoxic effects on primary human keratinocytes and dermal fibroblasts at the MIC in vitro. In vivo murine vulvovaginitis model experiments showed that NFAP2 significantly decreases the number of FLC-resistant C. albicans cells, and combined application with FLC enhances the efficacy. These results suggest that NFAP2 provides a feasible base for the development of a fundamental new, safely applicable mono- or polytherapeutic topical agent for the treatment of superficial candidiasis.

Paratesticular Fibrous Pseudotumor: A New Entity of IgG4-Related Disease?

INTRODUCTION: Paratesticular fibrous pseudotumor (PFP) represents a benign tumor-like lesion confined to intrascrotal, paratesticular areas. Due to its rarity, only less than 200 cases have been reported to date, of which both pathogenesis and clinical management are little understood. Recently, PFP has been postulated to be among the spectrum of so-called immunoglobulin G4-related diseases (IgG4-RD). Here we describe a case of PFP focusing on the clinical, morphological features and the utility of immunohistochemistry to support the theory that PFP might be a potential member of IgG4-RD family. CASE PRESENTATION: A 41-year-old man presented with a slowly growing, right intrascrotal mass An MRI scan revealed a diffuse-proliferative nodular mass around the paratesticular area. The patient underwent right orchiectomy and a diffuse multinodular tumor with testicular compression was discovered without intratesticular infiltration. Postoperatively, the patient has been well for 2 years up to the recent follow up. On histological examination, the lesion consisted of hyalinized fibrotic tissue with storiform patterns. There were scattered germinal centers; lymphocytic vasculitis was also noted. The immunoglobulin G4 staining showed infiltration of positive plasma cells with highest count 52 per high-power field, whereas the mixed Kappa and Lambda immunoglobulin light chain expression indicated the polyclonality of the plasma cell population. CONCLUSIONS: The morphological and immunohistochemical features in our case support the theory of PFP being part of IgG4-RD. Familiarity to this tumor-like lesion is crucial, since it may respond to corticosteroid therapy, which may save patients from more aggressive surgical procedures.

Endocannabinoid Tone Regulates Human Sebocyte Biology.

We have previously shown that endocannabinoids (eCBs) (e.g., anandamide) are involved in the maintenance of homeostatic sebaceous lipid production in human sebaceous glands and that eCB treatment dramatically increases sebaceous lipid production. Here, we aimed to investigate the expression of the major eCB synthesizing and degrading enzymes and to study the effects of eCB uptake inhibitors on human SZ95 sebocytes, thus exploring the role of the putative eCB membrane transporter, which has been hypothesized to facilitate the cellular uptake and subsequent degradation of eCBs. We found that the major eCB synthesizing (N-acyl phosphatidylethanolamine-specific phospholipase D, and diacylglycerol lipase-α and -ß) and degrading (fatty acid amide hydrolase, monoacylglycerol lipase) enzymes are expressed in SZ95 sebocytes and also in sebaceous glands (except for diacylglycerol lipase-α, the staining of which was dubious in histological preparations). eCB uptake-inhibition with VDM11 induced a moderate increase in sebaceous lipid production and also elevated the levels of various eCBs and related acylethanolamides. Finally, we found that VDM11 was able to interfere with the proinflammatory action of the TLR4 activator lipopolysaccharide. Collectively, our data suggest that inhibition of eCB uptake exerts anti-inflammatory actions and elevates both sebaceous lipid production and eCB levels; thus, these inhibitors might be beneficial in cutaneous inflammatory conditions accompanied by dry skin.

[Pathological diagnosis, work-up and reporting of breast cancer. Recommendations of the 3rd Hungarian Consensus Conference on Breast Cancer]. / Az emlõrák patológiai diagnosztikája, feldolgozása és kórszövettani leletezése. Szakmai útmutatás a III. Emlõrák Konszenzus Konferencia alapján.

There have been relevant changes in the diagnosis and treatment of breast cancer to implement the updating of the 2010 recommendations made during the 2nd national consensus conference on the disease. Following a wide interdisciplinary consultation, the present recommendations have been finalized after their public discussion at the 3rd Hungarian Consensus Conference on Breast Cancer. The recommendations cover non-operative and intraoperative diagnostics, the work-up of operative specimens, the determination of prognostic and predictive markers and the content of the cytology and histology reports. Furthermore, it touches some special issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, some relevant points about the future.

Paravertebral Low-grade Fibromyxoid Sarcoma with Supernumerary Ring Chromosome: Case Report and Literature Review.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue neoplasm with a deceptively benign histological appearance and low-grade malignant potential which is often mistaken for other reactive or benign lesions. It most frequently harbors balanced t(7;16) translocation, and leads to the fusion of the FUS and CREB3L2 genes which can be detected by cytogenetic methods. Young adults are most commonly affected and it typically arises in the deep proximal extremities or trunk with frequent recurrences. It may metastasize to the lungs several years later. Paravertebral LGFMS is exceedingly rare and only few cases have been published in the literature. In those cases the novel immunohistochemical markers and cytogenetic studies were not performed and morphological mimickers could not be confidently excluded.We present a rare case of paravertebral LGFMS from a 54-years-old male patient, which previously was misdiagnosed as a neurofibroma with subsequent tumor recurrence. The concrete diagnosis was established by using MUC4 immunohistochemical stain and fluorescent in situ hybridization (FISH), which showed diffuse membranous positivity and supernumerary ring chromosome with unbalanced FUS gene rearrangement, respectively. The latter finding is also rare and may cause diagnostic dilemma if one is not aware of such uncommon, but well-documented phenomenon. Differential diagnosis with other low-grade spindle cell tumors will also be discussed along with the literature review.

Predictive Factors for Positive Margin and the Surgical Learning Curve in Non-Palpable Breast Cancer After Wire-Guided Localization - Prospective Study of 214 Consecutive Patients.

To investigate the most commonly used technique, the wire-guided localization (WGL) in non-palpable breast cancer. To analyze the effective factors on positive surgical margins in our practice and determine the surgical learning curve of this method. Prospective consecutive study was performed from January 2005 to December 2011. Inclusion criteria was a non-palpable breast lesion with malignancy on preoperative histology. All lesions were localized by ultrasound or stereotactic guided wire placement. Margins 1 mm or closer were accepted as positive margins which required re-excision. To determine the learning curve of WGL method we investigated the change in the reoperation rate after primary procedure performed by "high-volume" surgeon. Two hundred and fourteen consecutive patients were enrolled. In 23 patients (10.7%) reexcision was needed. Positive surgical margins were significantly influenced by the patient's age (p = 0.03), tumor volume (p < =0.001), proportion of tumor volume/specimen volume (p < 0.001), presence of DCIS (p < 0.001), multifocality (p = 0.03) and the learning curve (p = 0.006) with univariate analysis. Only the tumor volume, presence of DCIS and the learning curve were proved as independent prognostic factor for reoperation by multivariate analysis. The reoperation rate decreased below 20% after the fortieth operation. Results of our single institutional study suggest, that this localization technique can be performed safely with very good results after 40 procedures as a learning curve for surgeons.

Immune-mediated Skin Inflammation is Similar in Severe Atopic Dermatitis Patients With or Without Filaggrin Mutation.

Inflammatory cytokines can impair the skin barrier, but the question as to whether barrier alterations affect keratinocyte immune responses remains unanswered. The aim of this study was to investigate whether immune-mediated skin inflammation differs between severe atopic dermatitis patients with or without filaggrin mutation. The levels of filaggrin, inflammatory T helper 2 polarizing cytokines (thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL-33)) and chemokine (C-C motif) ligand 27 (CCL27), histological severity markers, T and dendritic cell counts in biopsies from lesional skin of severe atopic dermatitis patients with and without filaggrin mutation and healthy skin were quantified by immunohistochemistry. The results were confirmed by quantitative PCR analyses. No significant differences were found between the 2 patient groups. Expression of atopic dermatitis-specific cytokines showed significant correlation with histological severity. These findings suggest that the immune-mediated skin inflammation (represented by keratinocyte-derived factors, T cell and dendritic cell counts) is similar in the 2 patient groups with severe atopic dermatitis, and that immune activation is connected to the severity of the disease rather than to the origin of barrier alterations.

Massive Localized Lymphedema Arising from Abdominal Wall: A Case Report and Review of the Literature.

Massive localized lymphedema (MLL) is a rare pseudosarcomatous lesion due to localized lymphatic obstruction from variable causes. It is most common on medial aspect of thigh and inguinal region. Abdominal localization is rare and may cause clinical diagnostic confusion with other malignant tumors due to its large size. We report a case of abdominal wall MLL of a 56-year-old male patient under clinical suspicion of well differentiated liposarcoma. The literature search and differential diagnosis will be addressed. In doubt cases, immunohistochemical stain or fluorescent in situ hybridization can help to separate this entity from the other mimickers.