In search of search privacy

Search engines have become integral to the way in which we use the Web of today. Not only are they an important real time source of links to relevant information, but they also serve as a starting point to the Web. A veritable treasure trove of the latest news, satellite images, directions from anywhere to anywhere, local traffic updates and global trends ranging from the spread of influenza to which celebrity happens to be the most popular at a particular time. The more popular search engines are collecting incredible amounts of information. In addition to indexing significant portions of the Web they record what hundreds of millions of users around the world are searching for. As more people use a particular search engine, it has the potential to record more information on what is deemed relevant (and in doing so provide better relevance in the future, thereby attracting more users). Unfortunately, the relevance derived from this cycle between the search user and the search engine comes at a cost: privacy. In this work, we take an in depth look at what privacy means within the context of search. We discuss why it is that the search engine must be considered a threat to search privacy. We then investigate potential solutions and eventually propose our own in a bid to enhance search privacy.Thesis (PhD)--University of Pretoria, 2011.Computer Scienceunrestricte

Paleodemografía y patología dental en la población hispano musulmana de Murcia: S. XI-XIII

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología. Fecha de lectura: 23-10-199

Paleodemografía y patología dental en la población hispano musulmana de Murcia: S. XI-XIII

Tesis inédita de Universidad Autónoma de Madrid, Facultad de Ciencia, Departamento de Biología, Unidad de Antropología.Fac. de Ciencias BiológicasTRUEProQuestpu

Influence of gender and sexual hormones on outcomes after pituitary surgery: a systematic review and meta-analysis

Background Although there is an increasing body of evidence showing gender differences in various medical domains as well as presentation and biology of pituitary adenoma (PA), gender differences regarding outcome of patients who underwent transsphenoidal resection of PA are poorly understood. The aim of this study was to identify gender differences in PA surgery. Methods The PubMed/MEDLINE database was searched up to April 2023 to identify eligible articles. Quality appraisal and extraction were performed in duplicate. Results A total of 40 studies including 4989 patients were included in this systematic review and meta-analysis. Our analysis showed odds ratio of postoperative biochemical remission in males vs. females of 0.83 (95% CI 0.59–1.15, P = 0.26), odds ratio of gross total resection in male vs. female patients of 0.68 (95% CI 0.34–1.39, P = 0.30), odds ratio of postoperative diabetes insipidus in male vs. female patients of 0.40 (95% CI 0.26–0.64, P < 0.0001), and a mean difference of preoperative level of prolactin in male vs. female patients of 11.62 (95% CI − 119.04–142.27, P = 0.86). Conclusions There was a significantly higher rate of postoperative DI in female patients after endoscopic or microscopic transsphenoidal PA surgery, and although there was some data in isolated studies suggesting influence of gender on postoperative biochemical remission, rate of GTR, and preoperative prolactin levels, these findings could not be confirmed in this meta-analysis and demonstrated no statistically significant effect. Further research is needed and future studies concerning PA surgery should report their data by gender or sexual hormones and ideally further assess their impact on PA surgery

Treatment resistance in pancreatic and biliary tract cancer: molecular and clinical pharmacology perspectives

Introduction: Treatment resistance poses a significant obstacle in oncology, especially in biliary tract cancer (BTC) and pancreatic cancer (PC). Current therapeutic options include chemotherapy, targeted therapy, and immunotherapy. Resistance to these treatments may arise due to diverse molecular mechanisms, such as genetic and epigenetic modifications, altered drug metabolism and efflux, and changes in the tumor microenvironment. Identifying and overcoming these mechanisms is a major focus of research: strategies being explored include combination therapies, modulation of the tumor microenvironment, and personalized approaches. Areas covered: We provide a current overview and discussion of the most relevant mechanisms of resistance to chemotherapy, target therapy, and immunotherapy in both BTC and PC. Furthermore, we compare the different strategies that are being implemented to overcome these obstacles. Expert opinion: So far there is no unified theory on drug resistance and progress is limited. To overcome this issue, individualized patient approaches, possibly through liquid biopsies or single-cell transcriptome studies, are suggested, along with the potential use of artificial intelligence, to guide effective treatment strategies. Furthermore, we provide insights into what we consider the most promising areas of research, and we speculate on the future of managing treatment resistance to improve patient outcomes.Award of EMBO Scientific Exchange Grant ref.: 10383, 2023Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía and European Regional Development Fund (ERDF), ref. P18-FR-2470, from the Ministry of Science, Innovation and Universities [ref. RTI 2018-101309-B-C22], and from the Chair “Doctors Galera-Requena in cancer stem cell research” [CMC-CTS963].KWF Dutch Cancer Society, Associazione Italiana per la Ricerca sul Cancro AIRCBennink Foundatio

Normal Behavioral Responses to Light and Darkness and the Pupillary Light Reflex are Dependent Upon the Olivary Pretectal Nucleus in the Diurnal Nile Grass Rat

The olivary pretectal nucleus (OPT) is a midbrain structure that receives reciprocal bilateral retinal projections, is involved in the pupillary light reflex, and connects reciprocally with the intergeniculate leaflet (IGL), a retinorecipient brain region that mediates behavioral responses to light pulses (i.e., masking) in diurnal Nile grass rats. Here, we lesioned the OPT and evaluated behavioral responses in grass rats to various lighting conditions, as well as their anxiety-like responses to light exposure. While control grass rats remained diurnal, grass rats with OPT lesions exhibited a more night-active pattern under 12h:12h light-dark (LD) conditions. However, when placed in constant darkness, OPT-lesioned grass rats became more active during their subjective day, suggesting that an exaggerated masking response to light may be responsible for the effect of OPT lesions on locomotor activity in LD. To test this hypothesis, we presented dark and light pulses to controls and grass rats with OPT lesions; controls increased their activity in response to light, whereas those with OPT lesions significantly increased activity in response to darkness. Further, when placed in a 7-h ultradian LD cycle, animals with OPT lesions were more active during darkness than controls. OPT lesions also abolished the pupillary light reflex, but did not affect anxiety-like behaviors. Finally, in animals with OPT lesions, light did not induce Fos expression in the ventrolateral geniculate nucleus, as it did in controls. Altogether, these results suggest that masking responses to light and darkness are dependent upon nuclei within the subcortical visual shell in grass rats

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration

The mortality rate for malignant melanoma (MM) is very high, since it is highly invasive and resistant to chemotherapeutic treatments. The modulation of some transcription factors affects cellular processes in MM. In particular, a higher expression of the osteogenic master gene RUNX2 has been reported in melanoma cells, compared to normal melanocytes. By analyzing public databases for recurrent RUNX2 genetic and epigenetic modifications in melanoma, we found that the most common RUNX2 genetic alteration that exists in transcription upregulation is, followed by genomic amplification, nucleotide substitution and multiple changes. Additionally, altered RUNX2 is involved in unchecked pathways promoting tumor progression, Epithelial Mesenchymal Transition (EMT), and metastasis. In order to investigate further the role of RUNX2 in melanoma development and to identify a therapeutic target, we applied the CRISPR/Cas9 technique to explore the role of the RUNT domain of RUNX2 in a melanoma cell line. RUNT-deleted cells showed reduced proliferation, increased apoptosis, and reduced EMT features, suggesting the involvement of the RUNT domain in different pathways. In addition, del-RUNT cells showed a downregulation of genes involved in migration ability. In an in vivo zebrafish model, we observed that wild-type melanoma cells migrated in 81% of transplanted fishes, while del-RUNT cells migrated in 58%. All these findings strongly suggest the involvement of the RUNT domain in melanoma metastasis and cell migration and indicate RUNX2 as a prospective target in MM therapy

Natural iminosugar (+)-lentiginosine inhibits ATPase and chaperone activity of Hsp90

Heat shock protein 90 (Hsp90) is a significant target in the development of rational cancer therapy due to its role at the crossroads of multiple signaling pathways associated with cell proliferation and cell viability. The relevance of Hsp90 as a therapeutic target for numerous diseases states has prompted the identification and optimization of novel Hsp90 inhibitors as an emerging therapeutic strategy. We performed a screening aimed to identify novel Hsp90 inhibitors among several natural compounds and we focused on the iminosugar (+)-lentiginosine, a natural amyloglucosidases inhibitor, for its peculiar bioactivity profile. Characterization of Hsp90 inhibition was performed using a panel of chemical and biological approaches, including limited proteolysis, biochemical and cellular assays. Our result suggested that the middle domain of Hsp90, as opposed to its ATP-binding pocket, is a promising binding site for new classes of Hsp90 inhibitors with multitarget anti-cancer potentia

Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma

Urothelial carcinoma (UC) is a frequent cause of cancer-related deaths worldwide. Metastatic UC has been historically associated with poor prognosis, with a median overall survival of approximately 15 months and a 5-year survival rate of 18%. Although platinum-based chemotherapy remains the mainstay of medical treatment for patients with metastatic UC, chemotherapy clinical trials produced modest benefit with short-lived, disappointing responses. In recent years, the better understanding of the role of immune system in cancer control has led to the development and approval of several immunotherapeutic approaches in UC therapy, where immune checkpoint inhibitors have been revolutionizing the treatment of metastatic UC. Because of a better tumor molecular profiling, FGFR inhibitors, PARP inhibitors, anti-HER2 agents, and antibody drug conjugates targeting Nectin-4 are also emerging as new therapeutic options. Moreover, a wide number of trials is ongoing with the aim to evaluate several other alterations and pathways as new potential targets in metastatic UC. In this review, we will discuss the recent advances and highlight future directions of the medical treatment of UC, with a particular focus on recently published data and ongoing active and recruiting trials

P2‐111: MESENCHYMAL STEM CELL‐DERIVED SECRETOME FULLY REPLICATE CELL‐MEDIATED NEURO‐REPARATIVE ACTIVITIES IN THE APP/PS1 MOUSE MODEL OF ALZHEIMER'S DISEASE

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