An Artificial Intelligent System for Prostate Cancer Diagnosis in Whole Slide Images.

In recent years a significant demand to develop computer-assisted diagnostic tools to assess prostate cancer using whole slide images has been observed. In this study we develop and validate a machine learning system for cancer assessment, inclusive of detection of perineural invasion and measurement of cancer portion to meet clinical reporting needs. The system analyses the whole slide image in three consecutive stages: tissue detection, classification, and slide level analysis. The whole slide image is divided into smaller regions (patches). The tissue detection stage relies upon traditional machine learning to identify WSI patches containing tissue, which are then further assessed at the classification stage where deep learning algorithms are employed to detect and classify cancer tissue. At the slide level analysis stage, entire slide level information is generated by aggregating all the patch level information of the slide. A total of 2340 haematoxylin and eosin stained slides were used to train and validate the system. A medical team consisting of 11 board certified pathologists with prostatic pathology subspeciality competences working independently in 4 different medical centres performed the annotations. Pixel-level annotation based on an agreed set of 10 annotation terms, determined based on medical relevance and prevalence, was created by the team. The system achieved an accuracy of 99.53% in tissue detection, with sensitivity and specificity respectively of 99.78% and 99.12%. The system achieved an accuracy of 92.80% in classifying tissue terms, with sensitivity and specificity respectively 92.61% and 99.25%, when 5x magnification level was used. For 10x magnification, these values were respectively 91.04%, 90.49%, and 99.07%. For 20x magnification they were 84.71%, 83.95%, 90.13%.

Contribution of cultural heritage values to steppe conservation on ancient burial mounds of Eurasia.

Civilizations, including ancient ones, have shaped global ecosystems in many ways through coevolution of landscapes and humans. However, the cultural legacies of ancient and lost civilizations are rarely considered in the conservation of the Eurasian steppe biome. We used a data set containing more than 1000 records on localities, land cover, protection status, and cultural values related to ancient steppic burial mounds (kurgans); we evaluated how these iconic and widespread landmarks can contribute to grassland conservation in the Eurasian steppes, which is one of the most endangered biomes on Earth. Using Bayesian logistic generalized regressions and proportional odds logistic regressions, we examined the potential of mounds to preserve grasslands in landscapes with different levels of land-use transformation. We also compared the conservation potential of mounds inside and outside protected areas and assessed whether local cultural values support the maintenance of grasslands on them. Kurgans were of great importance in preserving grasslands in transformed landscapes outside protected areas, where they sometimes acted as habitat islands that contributed to habitat conservation and improved habitat connectivity. In addition to steep slopes hindering ploughing, when mounds had cultural value for local communities, the probability of grassland occurrence on kurgans almost doubled. Because the estimated number of steppic mounds is about 600,000 and similar historical features exist on all continents, our results may be applicable at a global level. Our results also suggested that an integrative socioecological approach in conservation might support the positive synergistic effects of conservation, landscape, and cultural values.

Contribución de los valores culturales para la conservación esteparia en los antiguos montículos funerarios de Eurasia Resumen Las civilizaciones modernas y antiguas han moldeado de muchas maneras los ecosistemas globales mediante la coevolución del paisaje y la humanidad. Sin embargo, pocas veces se considera el legado cultural de las civilizaciones perdidas o antiguas para la conservación del bioma de la estepa euroasiática. Usamos un conjunto de datos que contiene más de 1,000 registros de las localidades, cobertura del suelo, estado de protección y valores culturales relacionados con los antiguos montículos funerarios de esta estepa (kurgans). Después analizamos cómo estos símbolos icónicos y distribuidos extensamente pueden contribuir a la conservación de los pastizales en la estepa euroasiática, uno de los biomas en mayor peligro de extinción. Analizamos el potencial de conservación de los montículos en paisajes con diferentes niveles de transformación en el uso de suelo mediante regresiones logísticas generalizadas bayesianas y regresiones logísticas de probabilidades proporcionales. También comparamos el potencial de conservación de los montículos dentro y fuera de las áreas protegidas y evaluamos si los valores culturales locales conservan los pastizales dentro de estas mismas áreas. Los kurgans fueron de gran importancia para la conservación de los pastizales en los paisajes transformados ubicados fuera de las áreas protegidas, en donde llegaron a fungir como hábitats aislados que contribuyeron a la conservación y conectividad del hábitat. Además de que las pendientes pronunciadas impiden el arado, cuando los montículos contaban con valor cultural para las comunidades locales, la probabilidad de que el pastizal se ubicara sobre un kurgan casi se duplicó. Ya que se estima que el número de montículos esteparios ronda los 6,000 y que rasgos históricos similares existen en todos los continentes, nuestros resultados pueden aplicarse a nivel global. Nuestros resultados también sugieren que una estrategia socio-ecológica integradora para la conservación podría respaldar los efectos sinérgicos positivos de la conservación, el paisaje y los valores culturales.

Compositional Analysis of Glycosaminoglycans in Different Lung Cancer Types-A Pilot Study.

Lung cancer is one of the most commonly diagnosed cancer types. Studying the molecular changes that occur in lung cancer is important to understand tumor formation and identify new therapeutic targets and early markers of the disease to decrease mortality. Glycosaminoglycan chains play important roles in various signaling events in the tumor microenvironment. Therefore, we have determined the quantity and sulfation characteristics of chondroitin sulfate and heparan sulfate in formalin-fixed paraffin-embedded human lung tissue samples belonging to different lung cancer types as well as tumor adjacent normal areas. Glycosaminoglycan disaccharide analysis was performed using HPLC-MS following on-surface lyase digestion. Significant changes were identified predominantly in the case of chondroitin sulfate; for example, the total amount was higher in tumor tissue compared to the adjacent normal tissue. We also observed differences in the degree of sulfation and relative proportions of individual chondroitin sulfate disaccharides between lung cancer types and adjacent normal tissue. Furthermore, the differences in the 6-O-/4-O-sulfation ratio of chondroitin sulfate were different between the lung cancer types. Our pilot study revealed that further investigation of the role of chondroitin sulfate chains and enzymes involved in their biosynthesis is an important aspect of lung cancer research.

Does sexual Intimate Partner Violence (IPV) increase risk of multiple high-risk fertility behaviours in India: evidence from National Family Health Survey 2015-16.

BACKGROUND: One in three women from lower and middle-income countries are subjected to physical and/or sexual intimate partner violence (IPV) in their life span. Prior studies have highlighted a range of adverse health impacts of sexual IPV. However, less is known about the link between multiple high-risk fertility behaviours and sexual intimate partner violence. The present study examines the statistical association between multiple high-risk fertility behaviours and sexual intimate partner violence among women in India. METHODS: The present study used a nationally representative dataset, the National Family Health Survey (NFHS-4) 2015-16. A total of 23,597 women were included in the study; a subsample of married women of reproductive age who have had at least one child 5 years prior to the survey and who had valid information about sexual IPV. Logistic regression models were employed alongside descriptive statistics. RESULTS: Approximately 7% of women who are or had been married face sexual IPV. The prevalence of sexual violence was higher among women who had short birth intervals and women who had given birth more than three times (12%). Around 11% of women who had experienced any high-risk fertility behaviours also experienced sexual violence. The unadjusted association suggested that multiple high-risk fertility behaviours were 32% (UORs = 1.32, 95% CI: 1.16-1.50) higher for those women who experienced sexual violence. After adjusting for other sociodemographic variables, except for women's education and wealth quantile, the odds of multiple high-risk fertility behaviours were 16% (AOR = 1.16; 95% CI: 1.02-1.34) higher among women who faced sexual violence. The inclusion of women's educational attainment and wealth status in the model made the association between sexual IPV and high-risk fertility behaviours insignificant. CONCLUSION: Sexual intimate partner violence is statistically associated with high-risk fertility behaviours among women in India. Programs and strategies designed to improve women's reproductive health should investigate the different dimensions of sexual IPV in India.

Expression of apoptosis repressor with caspase recruitment domain (ARC) in familial adenomatous polyposis (FAP) adenomas and its correlation with DNA mismatch repair proteins, p53, Bcl-2, COX-2 and beta-catenin.

BACKGROUND: Colorectal familial adenomatous polyposis (FAP) adenomas exhibit a uniform pathogenetic basis caused by a germline mutation in the adenomatous polyposis gene (APC), but the molecular changes leading to their development are incompletely understood. However, dysregulated apoptosis is known to substantially affect the development of colonic adenomas. One of the key regulatory proteins involved in apoptosis is apoptosis repressor with caspase recruitment domain (ARC). METHODS: The expression of nuclear and cytoplasmic ARC in 212 adenomas from 80 patients was analyzed by immunohistochemistry. We also compared expression levels of ARC with the expression levels of p53, Bcl-2, COX-2, and MMR proteins. Statistical analyses were performed by Spearman's rank correlation and linear regression test. RESULTS: ARC was overexpressed in the nuclei and cytoplasm of most FAP adenomas investigated. Cytoplasmic ARC staining was moderately stronger (score 2) in 49.1% (n = 104/212) and substantially stronger (score 3) in 32.5% (n = 69/212) of adenomas compared to non-tumorous colorectal mucosa. In 18.4% (n = 39/212) of adenomas, cytoplasmic ARC staining was equivalent to that in non-tumorous mucosa. Nuclear expression of ARC in over 75% of cells was present in 30.7% (n = 65/212) of investigated adenomas, and nuclear expression in 10-75% of cells was detected in 62.7% (n = 133/212). ARC expression in under 10% of nuclei was found in 6.6% (n = 14/212) of adenomas. The correlation between nuclear ARC expression and cytoplasmic ARC expression was highly significant (p = 0.001). Moreover, nuclear ARC expression correlated positively with overexpression of Bcl-2, COX-2 p53 and ß-catenin. Cytoplasmic ARC also correlated with overexpression of Bcl-2. Sporadic MMR deficiency was detected in very few FAP adenomas and showed no correlation with nuclear or cytoplasmic ARC. CONCLUSIONS: Our results demonstrated that both cytoplasmic and nuclear ARC are overexpressed in FAP adenomas, thus in a homogenous collective. The highly significant correlation between nuclear ARC and nuclear ß-catenin suggested that ARC might be regulated by ß-catenin in FAP adenomas. Because of its further correlations with p53, Bcl-2, and COX-2, nuclear ARC might play a substantial role not only in carcinomas but also in precursor lesions. Video Abstract.

Supramolecular assemblies underpin turnover of outer membrane proteins in bacteria.

Gram-negative bacteria inhabit a broad range of ecological niches. For Escherichia coli, this includes river water as well as humans and animals, where it can be both a commensal and a pathogen. Intricate regulatory mechanisms ensure that bacteria have the right complement of ß-barrel outer membrane proteins (OMPs) to enable adaptation to a particular habitat. Yet no mechanism is known for replacing OMPs in the outer membrane, an issue that is further confounded by the lack of an energy source and the high stability and abundance of OMPs. Here we uncover the process underpinning OMP turnover in E. coli and show it to be passive and binary in nature, in which old OMPs are displaced to the poles of growing cells as new OMPs take their place. Using fluorescent colicins as OMP-specific probes, in combination with ensemble and single-molecule fluorescence microscopy in vivo and in vitro, as well as molecular dynamics simulations, we established the mechanism for binary OMP partitioning. OMPs clustered to form ∼0.5-µm diameter islands, where their diffusion is restricted by promiscuous interactions with other OMPs. OMP islands were distributed throughout the cell and contained the Bam complex, which catalyses the insertion of OMPs in the outer membrane. However, OMP biogenesis occurred as a gradient that was highest at mid-cell but largely absent at cell poles. The cumulative effect is to push old OMP islands towards the poles of growing cells, leading to a binary distribution when cells divide. Hence, the outer membrane of a Gram-negative bacterium is a spatially and temporally organized structure, and this organization lies at the heart of how OMPs are turned over in the membrane.

Ferryl Hemoglobin and Heme Induce A1-Microglobulin in Hemorrhaged Atherosclerotic Lesions with Inhibitory Function against Hemoglobin and Lipid Oxidation.

Infiltration of red blood cells into atheromatous plaques and oxidation of hemoglobin (Hb) and lipoproteins are implicated in the pathogenesis of atherosclerosis. α1-microglobulin (A1M) is a radical-scavenging and heme-binding protein. In this work, we examined the origin and role of A1M in human atherosclerotic lesions. Using immunohistochemistry, we observed a significant A1M immunoreactivity in atheromas and hemorrhaged plaques of carotid arteries in smooth muscle cells (SMCs) and macrophages. The most prominent expression was detected in macrophages of organized hemorrhage. To reveal a possible inducer of A1M expression in ruptured lesions, we exposed aortic endothelial cells (ECs), SMCs and macrophages to heme, Oxy- and FerrylHb. Both heme and FerrylHb, but not OxyHb, upregulated A1M mRNA expression in all cell types. Importantly, only FerrylHb induced A1M protein secretion in aortic ECs, SMCs and macrophages. To assess the possible function of A1M in ruptured lesions, we analyzed Hb oxidation and heme-catalyzed lipid peroxidation in the presence of A1M. We showed that recombinant A1M markedly inhibited Hb oxidation and heme-driven oxidative modification of low-density lipoproteins as well plaque lipids derived from atheromas. These results demonstrate the presence of A1M in atherosclerotic plaques and suggest its induction by heme and FerrylHb in the resident cells.

Hemoglobin oxidation generates globin-derived peptides in atherosclerotic lesions and intraventricular hemorrhage of the brain, provoking endothelial dysfunction.

The lysis of red blood cells was shown to occur in human ruptured atherosclerotic lesions and intraventricular hemorrhage (IVH) of the brain. Liberated cell-free hemoglobin was found to undergo oxidation in both pathologies. We hypothesize that hemoglobin-derived peptides are generated during hemoglobin oxidation both in complicated atherosclerotic lesions and IVH of the brain, triggering endothelial cell dysfunction. Oxidized hemoglobin and its products were followed with spectrophotometry, LC-MS/MS analysis and detection of the cross-linking of globin chains in complicated atherosclerotic lesions of the human carotid artery and the hemorrhaged cerebrospinal liquid of preterm infants. The vascular pathophysiologic role of oxidized hemoglobin and the resultant peptides was assessed by measuring endothelial integrity, the activation of endothelial cells and the induction of proinflammatory genes. Peptide fragments of hemoglobin (VNVDEVGGEALGRLLVVYPWTQR, LLVVYPWTQR, MFLSFPTTK, VGAHAGEYGAELERMFLSFPTTK, and FLASVSTVLTSKYR) were identified in ruptured atherosclerotic lesions and in IVH of the human brain. Fragments resulting from the oxidation of hemoglobin were accompanied by the accumulation of ferryl hemoglobin. Similar to complicated atherosclerotic lesions of the human carotid artery, a high level of oxidized and cross-linked hemoglobin was observed in the cerebrospinal fluid after IVH. Haptoglobin inhibited hemoglobin fragmentation provoked by peroxide. The resultant peptides failed to bind haptoglobin or albumin. Peptides derived from hemoglobin oxidation and ferryl hemoglobin induced intercellular gap formation, decreased junctional resistance in the endothelium, and enhanced monocyte adhesion to endothelial cells. Enhanced expression of TNF and the activation of NLRP3 and CASP1 followed by the increased generation of IL-1ß and nuclear translocation of the NF-κß transcription factor occurred in response to hemoglobin-derived peptides, and ferryl hemoglobin in endothelium was upregulated in both pathologies. We conclude that the oxidation of hemoglobin in complicated atherosclerotic lesions and intraventricular hemorrhage of the brain generates peptide fragments and ferryl hemoglobin with the potential to trigger endothelial cell dysfunction.

Aerial Laser Scanning Data as a Source of Terrain Modeling in a Fluvial Environment: Biasing Factors of Terrain Height Accuracy.

Airborne light detection and ranging (LiDAR) scanning is a commonly used technology for representing the topographic terrain. As LiDAR point clouds include all surface features present in the terrain, one of the key elements for generating a digital terrain model (DTM) is the separation of the ground points. In this study, we intended to reveal the efficiency of different denoising approaches and an easy-to-use ground point classification technique in a floodplain with fluvial forms. We analyzed a point cloud from the perspective of the efficiency of noise reduction, parametrizing a ground point classifier (cloth simulation filter, CSF), interpolation methods and resolutions. Noise filtering resulted a wide range of point numbers in the models, and the number of points had moderate correlation with the mean accuracies (r = -0.65, p < 0.05), indicating that greater numbers of points had larger errors. The smallest differences belonged to the neighborhood-based noise filtering and the larger cloth size (5) and the smaller threshold value (0.2). The most accurate model was generated with the natural neighbor interpolation with the cloth size of 5 and the threshold of 0.2. These results can serve as a guide for researchers using point clouds when considering the steps of data preparation, classification, or interpolation in a flat terrain.

BRAF V600E and Retinoic Acid in Radioiodine-Refractory Papillary Thyroid Cancer.

Radioiodine refractoriness in differentiated thyroid cancer remains an unsolved therapeutic problem. Response to retinoids might depend on specific genetic markers. In this retrospective analysis, associations between BRAF V600E and clinical outcomes after redifferentiation with retinoic acid (RA) and radioiodine therapy (RIT) were investigated. Thirteen patients with radioiodine-refractory (RAI-R) papillary thyroid cancer (PTC) were treated with 13-cis-RA followed by iodine-131 treatment at the Department of Endocrinology, Heidelberg University Hospital, Heidelberg, Germany. DNA sequencing was performed in formalin-fixed paraffin-embedded tissue. Clinical outcome parameters were tumor size, thyroglobulin, and radioiodine uptake in correlation to mutational status. Differences of each parameter were compared before and after RA/RIT. Initial response showed no difference in patients with BRAF V600E compared to patients with wild type. However, after a median follow-up of 2 and a half years, 2 out of 3 patients with BRAF V600E showed response compared to 5 out of 9 with wild type under consideration of all 3 parameters. In this small cohort, more RAI-R PTC patients with BRAF V600E receiving redifferentiation therapy showed response. Verification in a larger study population analyzing mutational status in patients with RAI-R PTC might be helpful to identify patients where redifferentiation therapy might lead to an improved outcome.

Immunohistochemical detection of lymph node-DTCs in patients with node-negative HNSCC.

This study was performed to systematically assess the prevalence, topography and prognostic impact of disseminated tumor cells (DTCs) in lymph nodes (LN) of patients with primary, regional and distant metastasis-free head and neck squamous cell carcinoma (HNSCC) who underwent resection with elective neck dissection. From the routinely processed resection specimen, we could prospectively analyze a total of 1.137 exactly mapped LNs of 50 pN0-HNSCC patients, classified as tumor free by routine histopathology. Three immunohistochemistry (IHC) assays using antibodies directed against CK5/14, a broad spectrum of CKs (1-8, 10, 14-16 and 19), and CD44v6, respectively, were applied on 4.190 LN sections to detect DTCs. The IHC results were correlated with clinicopathologic parameters and clinical follow-up data. We detected seven micrometastases (MM) in five patients and 31 DTCs in 12 patients. Overall, 15 (30%) patients were positive for DTCs or MMs. Strikingly, the anatomical distribution of LN affected with DTCs was not random, but was dependent on the lateralization of the primary tumor and clustered significantly most proximal to the primary tumor. None of the investigated patients developed loco-regional lymphatic or distant metastasis during the mean follow-up period of 71 months. Our results reveal clinically occult tumor cell dissemination as an early and frequent event in HNSCC. Considering that higher rates of recurrences in therapeutic LN dissection concepts have been reported than in elective neck dissection strategies, our DTC-data support to perform elective neck dissections, since they appear to be effective in preventing loco-regional lymphatic recurrence from LN DTCs or MMs.

The role of apoptosis repressor with a CARD domain (ARC) in the therapeutic resistance of renal cell carcinoma (RCC): the crucial role of ARC in the inhibition of extrinsic and intrinsic apoptotic signalling.

BACKGROUND: Renal cell carcinomas (RCCs) display broad resistance against conventional radio- and chemotherapies, which is due at least in part to impairments in both extrinsic and intrinsic apoptotic pathways. One important anti-apoptotic factor that is strongly overexpressed in RCCs and known to inhibit both apoptotic pathways is ARC (apoptosis repressor with a CARD domain). METHODS: Expression and subcellular distribution of ARC in RCC tissue samples and RCC cell lines were determined by immunohistochemistry and fluorescent immunohistochemistry, respectively. Extrinsic and intrinsic apoptosis signalling were induced by TRAIL (TNF-related apoptosis-inducing ligand), ABT-263 or topotecan. ARC knock-down was performed in clearCa-12 cells using lentiviral transduction of pGIPZ. shRNAmir constructs. Extrinsic respectively intrinsic apoptosis were induced by TRAIL (TNF-related apoptosis-inducing ligand), ABT263 or topotecan. Potential synergistic effects were tested by pre-treatment with topotecan and subsequent treatment with ABT263. Activation of different caspases and mitochondrial depolarisation (JC-1 staining) were analysed by flow cytometry. Protein expression of Bcl-2 family members and ARC in RCC cell lines was measured by Western blotting. Statistical analysis was performed by Student's t-test. RESULTS: Regarding the extrinsic pathway, ARC knockdown strongly enhanced TRAIL-induced apoptosis by increasing the activation level of caspase-8. Regarding the intrinsic pathway, ARC, which was only weakly expressed in the nuclei of RCCs in vivo, exerted its anti-apoptotic effect by impairing mitochondrial activation rather than inhibiting p53. Topotecan- and ABT-263-induced apoptosis was strongly enhanced following ARC knockdown in RCC cell lines. In addition, topotecan pre-treatment enhanced ABT-263-induced apoptosis and this effect was amplified in ARC-knockdown cells. CONCLUSION: Taken together, our results are the first to demonstrate the importance of ARC protein in the inhibition of both the extrinsic and intrinsic pathways of apoptosis in RCCs. In this context, ARC cooperates with anti-apoptotic Bcl-2 family members to exert its strong anti-apoptotic effects and is therefore an important factor not only in the therapeutic resistance but also in future therapy strategies (i.e., Bcl-2 inhibitors) in RCC. In sum, targeting of ARC may enhance the therapeutic response in combination therapy protocols.

[A rare cause of hyponatraemia: McKittrick-Wheelock syndrome. Case report]. / A hyponatraemia ritka oka: McKittrick­Wheelock-szindróma.

Authors present a case of acute renal failure and hyponatraemia caused by a secretory tubulovillous adenoma of the colon, the rare so called McKittrick-Wheelock syndrome. A 75 year old woman was in need of treatment many times on medical wards because of watery diarrhoea, severe dehydration, hydroelectrolyte disturbance. The authors keep their case to be worthy to present, owing to the syndrome's rarity and difficulties of differential diagnosis. Orv Hetil. 2017; 158(18): 711-714.

[Tongue necrosis as an uncommon manifestation of temporal arteritis]. / A nyelv necrosisa mint az arteritis temporalis szokatlan manifesztációja.

Authors present a rare manifestation of the temporal arteritis, wich caused initial diagnostic difficulties, but it responded well for corticosteroid treatment. The features of the disease, pathogenesis, possible therapy are briefly summarized beside the description of clinical course. Orv. Hetil., 2017, 158(2), 77-80.

p16(INK4a) /Ki-67 co-expression specifically identifies transformed cells in the head and neck region.

p16(INK4a) immunohistochemical overexpression is an overall reliable surrogate marker of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). However, cases of ambiguous p16(INK4a) overexpression are regularly detected in the head and neck: p16(INK4a) expression can be observed in non-malignant tissue, such as tonsillar crypt epithelium and a proportion of branchial cleft cysts. Additionally, diverse patterns of p16(INK4) expression can complicate interpretation of "p16(INK4a) -positivity". These aspects impede the unrestricted application of p16(INK4a) as a diagnostic marker in the head and neck. We hypothesized that combined detection of p16(INK4a) and the proliferation marker Ki-67 could support clarification of ambiguous p16(INK4a) expression in the head and neck by specifically indicating p16(INK4a) -expressing cells with proliferative activity. p16(INK4a) /Ki-67 co-expression in a combined staining procedure was correlated to distinct p16(INK4a) expression patterns and HPV status (HPV DNA followed by E6*I oncogene mRNA detection) in 147 HNSCC and 50 non-malignant head and neck samples. p16(INK4a) /Ki-67 co-expression only occurred in transformed cells of the head and neck. Co-expression was never detected in non-transformed cells. Combined p16(INK4a) /Ki-67 expression was stringently associated with a diffuse p16(INK4a) expression pattern. All HPV oncogene-expressing HNSCC showed p16(INK4a) /Ki-67 co-expression. We demonstrate that p16(INK4a) /Ki-67 co-expression occurs exclusively in transformed cells of the head and neck. Our findings indicate a substantial impact of combined p16(INK4a) /Ki-67 expression in the assessment of ambiguous p16(INK4a) expression in the head and neck by specifically identifying p16(INK4a) -expressing cells with proliferative activity. This property will be of considerable significance for head and neck histo- and cytopathology.

Silent chorioamnionitis and associated pregnancy outcomes: a review of clinical data gathered over a 16-year period.

OBJECTIVE: To assess neonatal outcomes and associated findings in pregnant women identified after delivery as having had underlying subclinical chorioamnionitis by either histology or bacterial culture. METHODS: In 16 years, 8974 clinical, histological, and bacterial culture data were obtained retrospectively. RESULTS: Placental histology was analyzed in 4237 pregnancies (2785 term and 1452 preterm) and 4737 amniotic cavity cultures were obtained during 5446 cesarean deliveries (3268 term and 1469 preterm). Histological results and bacterial cultures were both available in 1270 of the preterm deliveries. Histology revealed inflammation, suggestive of infection, in 13.6% of placentas. Subclinical acute chorioamnionic inflammation was confirmed in 142 out of 2785 term pregnancies (5.1%) and in 436 out of 1452 preterm pregnancies (30.0%, P<0.001). Bacteriological culture of the intrauterine cavity was obtained from the lower uterine segment of the uterus during cesarean section. A positive culture was found in 19.9% of all cases (941/4737), this proportion was significantly higher in preterm deliveries (343/1273, 26.9%) than in term (17.3%, P<0.001). The lower the birth-weight or gestational age, the higher the frequency of silent infections in the uterine cavity. CONCLUSIONS: Our study findings support the association between intra-amniotic infections and preterm delivery.

Composite Bloom Filters for Secure Record Linkage.

The process of record linkage seeks to integrate instances that correspond to the same entity. Record linkage has traditionally been performed through the comparison of identifying field values (e.g., Surname), however, when databases are maintained by disparate organizations, the disclosure of such information can breach the privacy of the corresponding individuals. Various private record linkage (PRL) methods have been developed to obscure such identifiers, but they vary widely in their ability to balance competing goals of accuracy, efficiency and security. The tokenization and hashing of field values into Bloom filters (BF) enables greater linkage accuracy and efficiency than other PRL methods, but the encodings may be compromised through frequency-based cryptanalysis. Our objective is to adapt a BF encoding technique to mitigate such attacks with minimal sacrifices in accuracy and efficiency. To accomplish these goals, we introduce a statistically-informed method to generate BF encodings that integrate bits from multiple fields, the frequencies of which are provably associated with a minimum number of fields. Our method enables a user-specified tradeoff between security and accuracy. We compare our encoding method with other techniques using a public dataset of voter registration records and demonstrate that the increases in security come with only minor losses to accuracy.

Inequalities in regional excess mortality and life expectancy during the COVID-19 pandemic in Europe.

Using data for 201 regions (NUTS 2) in Europe, we examine the mortality burden of the COVID-19 pandemic and how the mortality inequalities between regions changed between 2020 and 2022. We show that over the three years of the pandemic, not only did the level of excess mortality rate change considerably, but also its geographical distribution. Focusing on life expectancy as a summary measure of mortality conditions, we find that the variance of regional life expectancy increased sharply in 2021 but returned to the pre-pandemic level in 2022. The 2021 increase was due to a much higher-than-average excess mortality in regions with lower pre-pandemic life expectancy. While the life expectancy inequality has returned to its pre-pandemic level in 2022, the observed life expectancy in almost all regions is far below that expected without the pandemic.

[Treatment outcome in primary testicular non-Hodgkin lymphoma]. / Primer herelymphomás betegek kezelésével szerzett tapasztalatok.

INTRODUCTION: Primary testicular lymphoma constitutes a rare subgroup among extranodal non-Hodgkin's lymphomas. Because of its aggressive clinical behaviour due to high grade histological features developing mainly in older population, patients with this disease usually have a poor prognosis. Orchidectomy followed by combination immunochemotherapy is a traditional treatment method with a rather inferior outcome. AIM: In this retrospective survey the authors analysed the clinical presentation, pathological features and treatment results of patients with primary testicular lymphoma diagnosed and treated in their haematology centre between 2000-2012 METHOD: During this period 334 patients with aggressive non-Hodgkin's lymphomas were treated, of whom 8 patients (2.39%; age between 23 and 86 years; median, 60 years) underwent semicastration for primary testicular lymphoma (7 patients had diffuse, large B-cell lymphoma and one patient had Burkitt-like lymphoma). According to the Ann Arbor staging system a limited stage I-IIE was diagnosed in 7 patients and advanced stage was found in one patient. All but one patients were treated with rituximab added to CHOP regimen (6 or 8 cycles in every 21 or 28 days), whereas one patient received radiotherapy only. Central nervous system intrathecal prophylaxis was used in one case and no preventive irradiation of the contralateral testis was used. RESULTS: With a median follow-up of 50 months complete remission was observed in 7 patients. However, two patients died (one due to progression and one in remission from pulmonary solid tumour). Complete remission rate proved to be 87.5%, disease-free survival was between 13 and 152 months (median 38 months) and overall survival rates were between 17 and 156 months (median 43 months). The 5-year disease-free and overall survival rates were 37.5 %. CONCLUSIONS: The relatively favourable treatment outcome could be mainly explained by the high number of patients with early-stage of the disease, early surgical removal of testicular lymphomas and the use if immunochemotherapy. This therapeutic regimen was effective to prevent localized and distant relapses. Despite omission of regular prophylaxis of the central nervous system, no relapse was detected.