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No abstract available. Article truncated after 150 words. A 58-year-old man with a history of human immunodeficiency virus on antiretroviral therapy, bullous emphysematous lung with right upper lobe cavity presented with hemoptysis for three days. On presentation, he was afebrile, with normal oxygen saturation on room air and reduced bilateral breath sounds. Computed tomography (CT) of the chest showed a thick wall cavity at the right upper lobe, with a 3 cm heterogeneous mass at the posterior aspect of the cavity (Figure 1 A). When the patient was placed in the prone position, the soft tissue lesion displaced anteriorly (Figure 1B) showing gravity-dependency (Monod's sign). His serum Aspergillus fumigatus antibodies were also positive. The patient was diagnosed with aspergilloma and started on voriconazole initially. However, because of recurrent hemoptysis, the patient was scheduled to undergo surgical excision. Saprophytic aspergillosis is the causative organism for the development of an aspergilloma (1). It results from colonization of fungus in a …

The evolution of high-performance computing facilitates the simulation of manufacturing processes. The prediction accuracy of a numerical model of the cutting process is closely associated with the selection of constitutive and friction models. The reliability and the accuracy of these models highly depend on the value of the parameters involved in the definition of the cutting process. Direct of inverse methods are used to determine these model parameters. However, these identification procedures often neglect the link between the parameters of the material and the friction models. This article introduces a novel approach to inversely identify the best parameters value for both models at the same time and by taking into account multiple cutting conditions in the optimization routine. An artificial intelligence (AI) framework that combines the finite element modeling with an adaptive Bayesian multi-objective evolutionary algorithm (AB-MOEA) is developed, where the objective is to minimize the deviation between the experimental and the numerical results. The arbitrary Lagrangian-Eulerian (ALE) formulation and the Ti6Al4V alloy are selected to demonstrate its applicability. The investigation shows that the developed AI platform can identify the best parameters values with low computational time and resources. The identified parameters values predicted the cutting and feed forces within a deviation of less than 4% from the experiments for all the cutting conditions considered in this work. [ABSTRACT FROM AUTHOR]

Abstract Background Triple-negative breast cancer (TNBC) is highly aggressive with an increased metastatic incidence compared to other breast cancer subtypes. However, due to the absence of clinically reliable biomarkers and targeted therapy in TNBC, outcomes are suboptimal. Hence, there is an urgent need to understand biological mechanisms that lead to identifying novel therapeutic targets for managing metastatic TNBC. Methods The clinical significance of MUC16 and ELAVL1 or Hu antigen R (HuR) was examined using breast cancer TCGA data. Microarray was performed on MUC16 knockdown and scramble TNBC cells and MUC16-associated genes were identified using RNA immunoprecipitation and metastatic cDNA array. Metastatic properties of MUC16 were evaluated using tail vein experiment. MUC16 and HuR downstream pathways were confirmed by ectopic overexpression of MUC16-carboxyl-terminal (MUC16-Cter), HuR and cMyc as well as HuR inhibitors (MS-444 and CMLD-2) in TNBC cells. Results MUC16 was highly expressed in TNBC and correlated with its target HuR. Depletion of MUC16 showed decreased invasion, migration, and colony formation abilities of human and mouse TNBC cells. Mice injected with MUC16 depleted cells were less likely to develop lung metastasis (P = 0.001). Notably, MUC16 and HuR were highly expressed in the lung tropic TNBC cells and lung metastases. Mechanistically, we identified cMyc as a HuR target in TNBC using RNA immunoprecipitation and metastatic cDNA array. Furthermore, MUC16 knockdown and pharmacological inhibition of HuR (MS-444 and CMLD-2) in TNBC cells showed a reduction in cMyc expression. MUC16-Cter or HuR overexpression models indicated MUC16/HuR/cMyc axis in TNBC cell migration. Conclusions Our study identified MUC16 as a TNBC lung metastasis promoter that acts through HuR/cMyc axis. This study will form the basis of future studies to evaluate the targeting of both MUC16 and HuR in TNBC patients.

Abstract Cancer divergence has many facets other than being considered a genetic term. It is a tremendous challenge to understand the metastasis and therapy response in cancer biology; however, it postulates the opportunity to explore the possible mechanism in the surrounding tumor environment. Most deadly solid malignancies are distinctly characterized by their tumor microenvironment (TME). TME consists of stromal components such as immune, inflammatory, endothelial, adipocytes, and fibroblast cells. Cancer stem cells (CSCs) or cancer stem-like cells are a small sub-set of the population within cancer cells believed to be a responsible player in the self-renewal, metastasis, and therapy response of cancer cells. The correlation between TME and CSCs remains an enigma in understanding the events of metastasis and therapy resistance in cancer biology. Recent evidence suggests that TME dictates the CSCs maintenance to arbitrate cancer progression and metastasis. The immune, inflammatory, endothelial, adipocyte, and fibroblast cells in the TME release growth factors, cytokines, chemokines, microRNAs, and exosomes that provide cues for the gain and maintenance of CSC features. These intricate cross-talks are fueled to evolve into aggressive, invasive, migratory phenotypes for cancer development. In this review, we have abridged the recent developments in the role of the TME factors in CSC maintenance and how these events influence the transition of tumor progression to further translate into metastasis and therapy resistance in cancer.

Abstract Acinar-to-ductal metaplasia (ADM) is a precursor lesion of pancreatic ductal adenocarcinoma (PDAC); however, the regulators of the ADM-mediated PDAC development and its targeting are poorly understood. RNA polymerase II-associated factor 1 (PAF1) maintains cancer stem cells leading to the aggressiveness of PDAC. In this study, we investigated whether PAF1 is required for the YAP1-mediated PDAC development and whether CA3 and verteporfin, small molecule inhibitors of YAP1/TEAD transcriptional activity, diminish pancreatic cancer (PC) cell growth by targeting the PAF1/YAP1 axis. Here, we demonstrated that PAF1 co-expresses and interacts with YAP1 specifically in metaplastic ducts of mouse cerulein- or KrasG12D-induced ADM and human PDAC but not in the normal pancreas. PAF1 knockdown (KD) reduced SOX9 in PC cells, and the PC cells showed elevated PAF1/YAP1 complex recruitment to the promoter of SOX9. The PAF1 KD reduced the 8xTEAD and SOX9 promoter-luciferase reporter activities in the mouse KC (KrasG12D; Pdx-1 Cre) cells and human PC cells, indicating that the PAF1 is required for the YAP1-mediated development of ADM and PC. Moreover, treatment with CA3 or verteporfin reduced the expressions of PAF1, YAP1, TEAD4, and SOX9 and decreased colony formation and stemness in KC and PC cells. CA3 treatment also reduced the viability and proliferation of PC cells and diminished the duct-like structures in KC acinar explants. CA3 or verteporfin treatment decreased the recruitment of the PAF1/YAP1 complex to the SOX9 promoter in PC cells and reduced the 8xTEAD and SOX9 promoter-luciferase reporter activities in KC and PC cells. Overall, PAF1 cooperates with YAP1 during ADM and PC development, and verteporfin and CA3 inhibit ADM and PC cell growth by targeting the PAF1/YAP1/SOX9 axis in vitro and ex vivo models. This study identified a regulatory axis of PDAC initiation and its targeting, paving the way for developing targeted therapeutic strategies for pancreatic cancer patients.

The annual cystic echinococcosis (CE) incidence in endemic countries is between 1 and 200 per 100,000 population. The clinical manifestations of CE are associated with damage or dysfunction of target organs and affect primarily the liver in around 70% of cases and lungs in around 20% of cases. The involvement of the spleen is rarely seen, representing 2 to 6% of all CE cases. We describe a 60-year-old female patient who presented with 15 days' history of intermittent fever and abdominal distension, having significant hepatosplenomegaly. CE was diagnosed involving the liver, spleen, and lungs and was confirmed radiologically and microbiologically. CE is caused by the larval or cystic stage of the zoonotic dog-tapeworm. Humans can be infected by ingestion of contaminated food or water. At present, there are nine species under the genus Echinococcus with E. granulosus sensu stricto having worldwide distribution, while the rest are focally distributed. CE involving multiple organs is rare. CE should be taken into consideration in patients with these symptoms in endemic areas.

Human skin cancer is the most common and potentially life-threatening form of cancer. Melanoma skin cancer, in particular, exhibits a high mortality rate. Early detection is crucial for effective treatment. Traditionally, melanoma is detected through painful and time-consuming biopsies. This research introduces a computer-aided detection technique for early melanoma diagnosis-sis. In this study, we propose two methods for detecting skin cancer and focus specifically on melanoma cancerous cells using image data. The first method employs convolutional neural networks, including AlexNet, LeNet, and VGG-16 models, and we integrate the model with the highest accuracy into web and mobile applications. We also investigate the relationship between model depth and performance with varying dataset sizes. The second method uses support vector machines with a default RBF kernel, using feature parameters to categorize images as benign, malignant, or normal after image processing. The SVM classifier achieved an 86.6% classification accuracy, while the CNN maintained a 91% accuracy rate after 100 compute epochs. The CNN model is deployed as a web and mobile application with the assistance of Django and Android Studio.

Summary: Cisplatin- and gemcitabine-based chemotherapeutics represent a mainstay of cancer therapy for most solid tumors; however, resistance limits their curative potential. Here, we identify RNA polymerase II-associated factor 1 (PAF1) as a common driver of cisplatin and gemcitabine resistance in human cancers (ovarian, lung, and pancreas). Mechanistically, cisplatin- and gemcitabine-resistant cells show enhanced DNA repair, which is inhibited by PAF1 silencing. We demonstrate an increased interaction of PAF1 with RAD52 in resistant cells. Targeting the PAF1 and RAD52 axis combined with cisplatin or gemcitabine strongly diminishes the survival potential of resistant cells. Overall, this study shows clinical evidence that the expression of PAF1 contributes to chemotherapy resistance and worse clinical outcome for lethal cancers.

Uterine leiomyoma (UL) is the most common benign smooth muscle tumour of the premenopausal women. Rarely it shows malignant behaviour by metastasizing through the pelvic veins into systemic veins, inferior vena cava (IVC), there it is termed as intravenous leiomyomatosis (IVL). IVL may restrict itself within the IVC or it may extend into right heart chambers reaching up to pulmonary arteries. Here we report a case of single staged excision of intracardiac(IC) extension of IVL of a 45 -year -old premenopausal women, who have undergone abdominal hysterectomy five years ago, with the complaints of shortness of breath aggravated on bending forward for the past two years.

The beaconing approach is the key function in geographic routing to disseminate the location. However, the node mobility is a prominent challenge to the beacon based location broadcasting schemes resulting in high routing overhead. The conventional methods allow some errors on location prediction. As a result, the mobile nodes update their location when the predicted location exceeds the allowable error range. However, the prediction error is more sensible for boundary nodes than adjacent nodes, as the boundary nodes located in the proximity area act as greedy nodes. Consequently, allowing the static prediction-error for all nodes does not efficiently reduce the overhead while maintaining the neighbor list accuracy. To deal with these issues, this work proposes a system called "MObility pattern free Dynamic and Effective Location update" (MODEL) for the maintenance of the trade-off between overhead and precision. Instead of allowing the static prediction-error, the Dynamic Acceptance Error Rate (DAR) in MODEL dynamically calculates the error range to the boundary and adjacent nodes and enhances the neighbor list accuracy with routing overhead. Due to the sensitivity of boundary nodes to the location being accurate, the MODEL efficiently exploits the fuzzy algorithm to allow a minimum error in predicting location rather than in adjacent nodes. This work simulates the proposed MODEL in NS2 simulator and compares the performance of the existing Load Balanced-Dynamic Beaconing Greedy Perimeter Stateless Routing (LB-DB-GPSR). [ABSTRACT FROM AUTHOR]

Abstract Background Cytomegalovirus (CMV) is a double stranded DNA virus and ubiquitous in nature. Association of Guillain-Barre syndrome (GBS) and CMV is well known but CMV acute myositis is a rare condition. Restriction of movements of limbs due to severe pain in myositis may obscure the diagnosis of GBS and this may easily miss. Case presentation Here we describe a 29-year-old male presenting with pain and swelling of bilateral lower limbs which progressed rapidly with increasing serum creatine kinase levels with positive IgM CMV antibodies. In view of no improvement in clinical condition, patient was further evaluated and found to have concurrent GBS. He was treated with plasmapheresis and improved. Conclusion Cytomegalovirus infection presenting as acute myositis is a uncommon and further association with GBS is a rare occurrence.

Resveratrol, a natural compound in grapes and red wine, has drawn attention due to potential cardiovascular-related health benefits. However, its effect on vascular inflammation at physiologically achievable concentrations is largely unknown. In this study, resveratrol in concentrations as low as 1 μm suppressed TNF-α-induced monocyte adhesion to human EA.hy926 endothelial cells (ECs), a key event in the initiation and development of atherosclerosis. Low concentrations of resveratrol (0.25–2 μm) also significantly attenuated TNF-α-stimulated mRNA expressions of MCP-1/CCL2 and ICAM-1, which are vital mediators of EC-monocyte adhesion molecules and cytokines for cardiovascular plaque formation. Additionally, resveratrol diminished TNF-α-induced IκB-α degradation and subsequent nuclear translocation of NF-κB p65 in ECs. In the animal study, resveratrol supplementation in diet significantly diminished TNF-α-induced increases in circulating levels of adhesion molecules and cytokines, monocyte adhesion to mouse aortic ECs, F4/80-positive macrophages and VCAM-1 expression in mice aortas and restored the disruption in aortic elastin fiber caused by TNF-α treatment. The animal study also confirmed that resveratrol blocks the activation of NF-κB In Vivo. In conclusion, resveratrol at physiologically achievable concentrations displayed protective effects against TNF-α-induced vascular endothelial inflammation in vitro and In Vivo. The ability of resveratrol in reducing inflammation may be associated with its role as a down-regulator of the NF-κB pathway.

To investigate the hepatoprotective activity of Asparagus racemosus against isoniazid-induced hepatotoxicity in male albino rats. Rats (n = 6 per group)were divided into four groups: saline-treated control, saline-treated control with A. racemosus extract (50 mg/kg), isoniazid treatment alone (100 mg/kg, intraperitoneal [i.p.]), and isoniazid–A. racemosus extract (50 mg/kg)administered orally as cotreatment. Animals were treated for 21 days and euthanized 1 h after the last drug administration. Evaluated body weight, serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, g-glutamyl transferase, total protein, albumin, hepatic malondialdehyde content, superoxide dismutase, catalase, cytochrome P450 2E1 (CYP2E1)activity and glutathione (GSH). A. racemosus extract prevented isoniazid-induced hepatotoxicity, indicated by both diagnostic indicators of liver damage, liver functional profile, significantly (p < 0.05)inhibited CYP2E1 activity, markedly attenuated oxidative stress by improved enzymatic, non-enzymatic antioxidants levels and mitigate malondialdehyde, lipid hydroperoxide significantly (p < 0.05). These results suggest that A. racemosus extract exerts its hepatoprotective activity by inhibiting the production of free radicals and acts as a scavenger, reducing the free radical generation via inhibition of hepatic CYP2E1 activity, increasing the removal of free radicals through the induction of antioxidant enzymes and improving non-enzymatic thiol antioxidant GSH. [ABSTRACT FROM AUTHOR]