Imaging technologies in the differential diagnosis and follow-up of brown tumor in primary hyperparathyroidism: case report and review of the literature

Brown tumors are osteolytic lesions associated with hyperparathyroidism (HPT). They may involve various skeletal segments, but rarely the cranio-facial bones. We report a case of a young boy with a swelling of the jaw secondary to a brown tumor presenting as the first manifestation of primary HPT (PHPT). He was found to have brown tumor located in the skull, as well. Different imaging technologies were employed for the diagnosis and follow-up after parathyroidectomy. We enclose a review of the literature on the employment of such imaging technologies in the differential diagnosis of osteolytic lesions. A multidisciplinary approach comprising clinical, laboratory and imaging findings is essential for the differential diagnosis of brown tumor in PHPT

Diagnosis and grading of radiographic osteoporotic vertebral deformity by general radiologists after a brief self-learning period

Background: The expanded semi-quantitative (eSQ) osteoporotic vertebral deformity (OVD) classification has minimal, mild, moderate, moderately-severe, severe, and collapsed grades with <20%, 20-25%, >25%-1/3, >1/3-40%, >40%-2/3, >2/3 vertebral height loss respectively. This study evaluates the performance of using this grading criterion by radiology readers who did not have former training in OVD assessment. Methods: Spine radiographs of 44 elderly women with 278 normal appearing vertebrae and 65 OVDs were selected, with two senior readers agreed the reference reading. Three readers from Italy and three readers from China were invited to evaluate these radiographs after reading five reference articles including one detailing eSQ criteria with illustrative examples. Before the second round of reading, the readers were asked to read an additional explanatory document. For the readers in Italy an additional on-line demonstration was given on how to measure vertebral height loss in another five cases of OVD. Two Chinese readers had a third round of reading after a 90 minutes' on-line lecture. Results: The final absolute agreement rate with the reference reading (i.e., exactly the same grading as the reference) ranged between 46.2% to 68.2% for the six readers, and the final relative agreement (with one eSQ grade difference allowed) ranged between 78.5% to 92.5%. The >1 grade disagreement rate was all below 11%, and mostly below 7%. The missed OVD were mostly minimal grade. The rate for missing a ≥ mild OVD was <4.5%, and false positive rate was generally <1.4% among the final reading. If the minimal grade was removed and the remaining gradings were converted to Genant's semi-quantitative (GSQ) grading, the mean kappa values against the reference reading for SQ grades-1,2,3 were 0.813, 0.814, and 0.916 respectively. Conclusions: This study demonstrates good performance of the six learner readers for assessing radiographic after a brief self-learning period

TOXICIDAD AGUDA DE TRES ENJUAGUES BUCALES A BASE DE PLANTAGO MAJOR, UNCARIA TOMENTOSA Y EUCALYPTUS GLOBULUS EN EL CAMARÓN SALINO ARTEMIA FRANCISCANA

Las plantas naturales han sido durante mucho tiempo investigadas para comprobar sus propiedades curativas. El Perú gracias a su biodiversidad posee muchas plantas que han sido evaluadas con propiedades que colaboran con la salud bucal, pero para ser prescritas a los pacientes es necesario comprobar que su toxicidad. El objetivo de la presente investigación fue evaluar la toxicidad aguda de tres enjuagues bucales a base de Plantago major L. “Llantén”, Uncaria tomentosa (Willd. ex Schult.) DC. “Uña de gato” y Eucalyptus globulus Labill. “Eucalipto” sobre Artemia franciscana Kellogg, 1906 “Camarón salino”. El ensayo de toxicidad consistió en exponer a nauplios de II instar de A. franciscana a enjuagues bucales alcohólicos y acuosos a 24 h y 48 h de exposición. Se determinó la Concentración letal media (CL ) para cada enjuague bucal y se clasificó su nivel de toxicidad según los índices de toxicidad de 50 Meyer y de Clarkson. Los enjuagues bucales a base de P. major, U. tomentosa y E. globulus son poco - tóxicos según la escala de Clarkson. Los enjuagues alcohólicos (751,74-881,68) en base a la CL50 (ug•mL 1 ) resultaron igual de tóxicos en A. franciscana que los enjuagues sin alcohol (470,68- 894,87). El enjuague bucal alcohólico más tóxico fue el de U. tomentosa, y el enjuague bucal acuoso más tóxico fue el de E. globulus. Al finalizar se encontró poca toxicidad en estas plantas sobre A. franciscana, en base a los índices de toxicidad de Meyer y de Clarkson, lo que demuestra que se podrían usar los tres enjuagues bucales con cautela

Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II ITMO study.

BACKGROUND: Biliary tract cancer (BTC) is a highly lethal disease for which the best available therapy remains undetermined. The mammalian target of rapamycin (mTOR) pathway is up-regulated in several cancers, including BTC, and preclinical evidence indicates that mTOR inhibition may be effective in the treatment of BTC. We sought to evaluate the activity and tolerability of the mTOR inhibitor RAD001-everolimus-in patients with BTC progressing after prior chemotherapy. PATIENTS AND METHODS: This was an open-label, single-arm, phase II study (EUDRACT 2008-007152-94) conducted in eight sites in Italy. Patients with locally advanced, metastatic or recurrent BTC progressing despite previous chemotherapy received a daily oral dose of everolimus 10 mg administered continuously in 28-day cycles. The two primary end points were disease control rate (DCR) and objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS) and time-to-progression (TTP). RESULTS: Thirty-nine patients were enrolled. The DCR was 44.7%, and the ORR was 5.1%. One patient showed a partial response at 2 months and one patient showed a complete response sustained up to 8 months. The median (95% confidence interval) PFS was 3.2 (1.8-4.0) months, and the median OS was 7.7 (5.5-13.2) months. The median TTP was 2.0 (1.7-3.7) months. Most common toxicities were asthenia (43.6%), thrombocytopenia (35.9%), pyrexia (30.8%) and erythema, mainly of mild-to-moderate severity. Two patients required dose reduction due to adverse events. CONCLUSION: Everolimus demonstrated a favourable toxicity profile and encouraging anti-tumour activity. Further trials are needed to establish the role of everolimus in the treatment of BTC. EUDRACT 2008-007152-94

Kupffer Cells Hasten Resolution of Liver Immunopathology in Mouse Models of Viral Hepatitis

Kupffer cells (KCs) are widely considered important contributors to liver injury during viral hepatitis due to their pro-inflammatory activity. Herein we utilized hepatitis B virus (HBV)-replication competent transgenic mice and wild-type mice infected with a hepatotropic adenovirus to demonstrate that KCs do not directly induce hepatocellular injury nor do they affect the pathogenic potential of virus-specific CD8 T cells. Instead, KCs limit the severity of liver immunopathology. Mechanistically, our results are most compatible with the hypothesis that KCs contain liver immunopathology by removing apoptotic hepatocytes in a manner largely dependent on scavenger receptors. Apoptotic hepatocytes not readily removed by KCs become secondarily necrotic and release high-mobility group box 1 (HMGB-1) protein, promoting organ infiltration by inflammatory cells, particularly neutrophils. Overall, these results indicate that KCs resolve rather than worsen liver immunopathology

AI ATAC 1: An Evaluation of Prominent Commercial Malware Detectors

This work presents an evaluation of six prominent commercial endpoint malware detectors, a network malware detector, and a file-conviction algorithm from a cyber technology vendor. The evaluation was administered as the first of the Artificial Intelligence Applications to Autonomous Cybersecurity (AI ATAC) prize challenges, funded by / completed in service of the US Navy. The experiment employed 100K files (50/50% benign/malicious) with a stratified distribution of file types, including ~1K zero-day program executables (increasing experiment size two orders of magnitude over previous work). We present an evaluation process of delivering a file to a fresh virtual machine donning the detection technology, waiting 90s to allow static detection, then executing the file and waiting another period for dynamic detection; this allows greater fidelity in the observational data than previous experiments, in particular, resource and time-to-detection statistics. To execute all 800K trials (100K files $\times$ 8 tools), a software framework is designed to choreographed the experiment into a completely automated, time-synced, and reproducible workflow with substantial parallelization. A cost-benefit model was configured to integrate the tools' recall, precision, time to detection, and resource requirements into a single comparable quantity by simulating costs of use. This provides a ranking methodology for cyber competitions and a lens through which to reason about the varied statistical viewpoints of the results. These statistical and cost-model results provide insights on state of commercial malware detection

Beyond the Hype: A Real-World Evaluation of the Impact and Cost of Machine Learning-Based Malware Detection

There is a lack of scientific testing of commercially available malware detectors, especially those that boast accurate classification of never-before-seen (i.e., zero-day) files using machine learning (ML). The result is that the efficacy and gaps among the available approaches are opaque, inhibiting end users from making informed network security decisions and researchers from targeting gaps in current detectors. In this paper, we present a scientific evaluation of four market-leading malware detection tools to assist an organization with two primary questions: (Q1) To what extent do ML-based tools accurately classify never-before-seen files without sacrificing detection ability on known files? (Q2) Is it worth purchasing a network-level malware detector to complement host-based detection? We tested each tool against 3,536 total files (2,554 or 72% malicious, 982 or 28% benign) including over 400 zero-day malware, and tested with a variety of file types and protocols for delivery. We present statistical results on detection time and accuracy, consider complementary analysis (using multiple tools together), and provide two novel applications of a recent cost-benefit evaluation procedure by Iannaconne & Bridges that incorporates all the above metrics into a single quantifiable cost. While the ML-based tools are more effective at detecting zero-day files and executables, the signature-based tool may still be an overall better option. Both network-based tools provide substantial (simulated) savings when paired with either host tool, yet both show poor detection rates on protocols other than HTTP or SMTP. Our results show that all four tools have near-perfect precision but alarmingly low recall, especially on file types other than executables and office files -- 37% of malware tested, including all polyglot files, were undetected.Comment: Includes Actionable Takeaways for SOC

CXCR3 identifies human naive CD8+ T cells with enhanced effector differentiation potential

In mice, the ability of naive T (TN) cells to mount an effector response correlates with TCR sensitivity for self-derived Ags, which can be quantified indirectly by measuring surface expression levels of CD5. Equivalent findings have not been reported previously in humans. We identified two discrete subsets of human CD8+ TN cells, defined by the absence or presence of the chemokine receptor CXCR3. The more abundant CXCR3+ TN cell subset displayed an effector-like transcriptional profile and expressed TCRs with physicochemical characteristics indicative of enhanced interactions with peptide-HLA class I Ags.Moreover, CXCR3+ TN cells frequently produced IL-2 and TNF in response to nonspecific activation directly ex vivo and differentiated readily into Ag-specific effector cells in vitro. Comparative analyses further revealed that human CXCR3+ TN cells were transcriptionally equivalent to murine CXCR3+ TN cells, which expressed high levels of CD5. These findings provide support for the notion that effector differentiation is shaped by heterogeneity in the preimmune repertoire of human CD8+ T cells