Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity.

Tumor heterogeneity poses a significant challenge in osteosarcoma (OS) treatment. In this regard, the "omics" era has constantly expanded our understanding of biomarkers and altered signaling pathways (i.e., PI3K/AKT/mTOR, WNT/ß-catenin, NOTCH, SHH/GLI, among others) involved in OS pathophysiology. Despite different players and complexities, many commonalities have been described, among which the nuclear factor kappa B (NF-κB) stands out. Its altered activation is pervasive in cancer, with pleiotropic action on many disease-relevant traits. Thus, in the scope of this article, we highlight the evidence of NF-κB dysregulation in OS and its integration with other cancer-related pathways while we summarize the repertoire of compounds that have been described to interfere with its action. In silico strategies were used to demonstrate that NF-κB is closely coordinated with other commonly dysregulated signaling pathways not only by functionally interacting with several of their members but also by actively participating in the regulation of their transcription. While existing inhibitors lack selectivity or act indirectly, the therapeutic potential of targeting NF-κB is indisputable, first for its multifunctionality on most cancer hallmarks, and secondly, because, as a common downstream effector of the many dysregulated pathways influencing OS aggressiveness, it turns complex regulatory networks into a simpler picture underneath molecular heterogeneity.

Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.

Childhood cancer is considered rare, corresponding to ~3% of all malignant neoplasms in the human population. The World Health Organization (WHO) reports a universal occurrence of more than 15 cases per 100,000 inhabitants around the globe, and despite improvements in diagnosis, treatment and supportive care, one child dies of cancer every 3 min. Consequently, more efficient, selective and affordable therapeutics are still needed in order to improve outcomes and avoid long-term sequelae. Alterations in kinases' functionality is a trademark of cancer and the concept of exploiting them as drug targets has burgeoned in academia and in the pharmaceutical industry of the 21st century. Consequently, an increasing plethora of inhibitors has emerged. In the present study, the expression patterns of a selected group of kinases (including tyrosine receptors, members of the PI3K/AKT/mTOR and MAPK pathways, coordinators of cell cycle progression, and chromosome segregation) and their correlation with clinical outcomes in pediatric solid tumors were accessed through the R2: Genomics Analysis and Visualization Platform and by a thorough search of published literature. To further illustrate the importance of kinase dysregulation in the pathophysiology of pediatric cancer, we analyzed the vulnerability of different cancer cell lines against their inhibition through the Cancer Dependency Map portal, and performed a search for kinase-targeted compounds with approval and clinical applicability through the CanSAR knowledgebase. Finally, we provide a detailed literature review of a considerable set of small molecules that mitigate kinase activity under experimental testing and clinical trials for the treatment of pediatric tumors, while discuss critical challenges that must be overcome before translation into clinical options, including the absence of compounds designed specifically for childhood tumors which often show differential mutational burdens, intrinsic and acquired resistance, lack of selectivity and adverse effects on a growing organism.

Relationship of the anterior ethmoid sinus to the lacrimal sac: a computed tomography study

Abstract Objective: To analyze the anatomical relationship between the lacrimal sac and the agger nasi cell on Computed Tomography (CT); to correlate the right and left sides on each scan. Methods: CT scans of adult patients were reviewed for pneumatization of the agger nasi and its relationship to the lacrimal sac. The degree of agreement between the right and left sides was also evaluated. Results: A total of 130 CT scans were examined. An agger nasi cell was found medial to the lacrimal sac in 59.23% of scans. On 86.15% of scans, pneumatization was similar on both sides. Conclusion: The agger nasi air cell is located medial to the lacrimal sac in more than half of individuals. The right and left sides exhibit the same pneumatization pattern in approximately 80% of cases. Level of evidence: 4.

Relationship of the anterior ethmoid sinus to the lacrimal sac: a computed tomography study.

OBJECTIVE: To analyze the anatomical relationship between the lacrimal sac and the agger nasi cell on Computed Tomography (CT); to correlate the right and left sides on each scan. METHODS: CT scans of adult patients were reviewed for pneumatization of the agger nasi and its relationship to the lacrimal sac. The degree of agreement between the right and left sides was also evaluated. RESULTS: A total of 130 CT scans were examined. An agger nasi cell was found medial to the lacrimal sac in 59.23% of scans. On 86.15% of scans, pneumatization was similar on both sides. CONCLUSION: The agger nasi air cell is located medial to the lacrimal sac in more than half of individuals. The right and left sides exhibit the same pneumatization pattern in approximately 80% of cases.

Thermochemical Liquefaction as a Cleaner and Efficient Route for Valuing Pinewood Residues from Forest Fires.

Biomass thermochemical liquefaction is a chemical process with multifunctional bio-oil as its main product. Under this process, the complex structure of lignocellulosic components can be hydrolysed into smaller molecules at atmospheric pressure. This work demonstrates that the liquefaction of burned pinewood from forest fires delivers similar conversion rates into bio-oil as non-burned wood does. The bio-oils from four burned biomass fractions (heartwood, sapwood, branches, and bark) showed lower moisture content and higher HHV (ranging between 32.96 and 35.85 MJ/kg) than the initial biomasses. The increased HHV resulted from the loss of oxygen, whereas the carbon and hydrogen mass fractions increased. The highest conversion of bark and heartwood was achieved after 60 min of liquefaction. Sapwood, pinewood, and branches reached a slightly higher conversion, with yields about 8% greater, but with longer liquefaction time resulting in higher energy consumption. Additionally, the van Krevelen diagram indicated that the produced bio-oils were closer and chemically more compatible (in terms of hydrogen and oxygen content) to the hydrocarbon fuels than the initial biomass counterparts. In addition, bio-oil from burned pinewood was shown to be a viable alternative biofuel for heavy industrial applications. Overall, biomass from forest fires can be used for the liquefaction process without compromising its efficiency and performance. By doing so, it recovers part of the lost value caused by wildfires, mitigating their negative effects.

Security Mechanisms of a Mobile Health Application for Promoting Physical Activity among Older Adults.

Physical activity contributes to the maintenance of health conditions and functioning. However, the percentage of older adults who comply with the recommendations for physical activity levels is low when compared to the same percentages on younger groups. The SmartWalk system aims to encourage older adults to perform physical activity (i.e., walking in the city), which is monitored and adjusted by healthcare providers for best results. The study reported in this article focused on the implementation of SmartWalk security services to keep personal data safe during communications and while at rest, which were validated considering a comprehensive use case. The security framework offers various mechanisms, including an authentication system that was designed to complement the pairs of usernames and passwords with trusted execution environments and token-based features, authorization with different access levels, symmetric and asymmetric key cryptography, critical transactions review, and logging supported by blockchain technology. The resulting implementation contributes for a common understanding of the security features of trustful smart cities' applications, which conforms with existing legislation and regulations.

Recurrent diffuse large B-cell lymphoma mimicking primary breast cancer

Breast lymphoma can represent 0.8%­2.2% of extranodal lymphomas and 0.1%­0.5% of primary breast neoplasms. Imaging findings are not specific, and its distinction from primary invasive breast carcinoma should be based on clinical data and histopathological analysis. We present the case of a 62-year-old woman who showed an unusual pattern of recurrent diffuse large B-cell lymphoma (DLBCL) mimicking primary breast cancer on imaging studies, including mammography, ultrasound, magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT).

Intramammary lymph nodes: normal and abnormal multimodality imaging features.

Intramammary lymph nodes (IMLN) are one of the most common benign findings at screening mammography. However, abnormal IMLN features, such as diminished or absent hilum, thickened cortex, not circumscribed margins, increased size or interval change, warrants additional follow-up or pathologic analysis to exclude malignancy. Some benign inflammatory conditions may be associated with imaging-detected suspected abnormal IMLN, such as reactive hyperplasia and silicone-induced lymphadenopathy. In patients with known breast cancer, IMLN are a potential site of locoregional spread, which can change the prognosis and management. In some cases, initial breast carcinomas can also mimic IMLN. Breast radiologists must also be aware of the typical and atypical characteristics of IMLN to suggest further investigation when it is necessary.