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Topic Review
CNNs in lymph node metastasis
Deep learning models have potential to improve performance of automated computer-assisted diagnosis tools in digital histopathology and reduce subjectivity. The main objective of this study was to further improve diagnostic potential of convolutional neural networks (CNNs) in detection of lymph node metastasis in breast cancer patients by integrative augmentation of input images with multiple segmentation channels. For this retrospective study, we used the PatchCamelyon dataset, consisting of 327,680 histopathology images of lymph node sections from breast cancer. Images had labels for the presence or absence of metastatic tissue. In addition, we used four separate histopathology datasets with annotations for nucleus, mitosis, tubule, and epithelium to train four instances of U-net. Then our baseline model was trained with and without additional segmentation channels and their performances were compared. Integrated gradient was used to visualize model attribution. The model trained with concatenation/integration of original input plus four additional segmentation channels, which we refer to as ConcatNet, was superior (AUC 0.924) compared to baseline with or without augmentations (AUC 0.854; 0.884). Baseline model trained with one additional segmentation channel showed intermediate performance (AUC 0.870-0.895). ConcatNet had sensitivity of 82.0% and specificity of 87.8%, which was an improvement in performance over the baseline (sensitivity of 74.6%; specificity of 80.4%). Integrated gradients showed that models trained with additional segmentation channels had improved focus on particular areas of the image containing aberrant cells. Augmenting images with additional segmentation channels improved baseline model performance as well as its ability to focus on discrete areas of the image.
  • 878
  • 19 Oct 2020
Topic Review
Influenza Vaccines
Influenza viruses are Orthomyxovirus species belonging to the Orthomyxoviridae family. While influenza viruses can be classified into four genera (A, B, C and D), only influenza A and B viruses cause clinical disease in humans.
  • 877
  • 10 Feb 2021
Topic Review
Store-Independent Calcium Entry
Calcium is recognized as a universal intracellular second messenger involved in a plethora of physiological as well as physiopathological processes, such as cell proliferation, migration, invasion, apoptosis, and chemoresistance in a cancer situation. Store-independent calcium entry is a distinctive calcium entry in cells, which is not activated by calcium store depletion. This entry is supported by basal activated calcium channels, ligand-activated calcium channels, or voltage-gated calcium channels.
  • 876
  • 29 Mar 2022
Topic Review
Proteomic Analysis of tPVAT during Ang II Infusion
In this study, we provided the most comprehensive proteome profile of mice tPVAT and some novel insights into Ang II-mediated tPVAT dysfunction. We identified some novel proteins, potentially associated with Ang II infusion, such as acyl-CoA carboxylase α , very long-chain acyl-CoA synthetase (ACSVL), uncoupling protein 1 (UCP1), perilipin, RAS protein-specific guanine nucleotide-releasing factor 2 (RasGRF2), and hypoxia inducible factor 1 α (HIF-1 α ). Importantly, the key pathways were involved in fatty acid biosynthesis, FABP3-PPAR α / γ , RasGRF2-ERK-HIF-1 α , RasGRF2-PKC-HIF-1 α , and STAT3-HIF-1 α axis.
  • 873
  • 22 Dec 2021
Topic Review
Common Toxic Pathways in Neurodegeneration
Neurodegenerative diseases (NDDs) are becoming increasingly prevalent in an age-dependent manner, partly because life expectancy has increased in recent years due to our advanced medical knowledge. The most prevalent of NDDs includes Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), spinocerebellar ataxias (SCA), prion diseases (PrD) and others.
  • 872
  • 27 Oct 2021
Topic Review
HDLs and Adiponectin in Promoting Endothelial Dysfunction
Obesity is an epidemic public health problem that has progressively worsened in recent decades and is associated with low-grade chronic inflammation (LGCI) in metabolic tissues and an increased risk of several diseases. In particular, LGCI alters metabolism and increases cardiovascular risk by impairing endothelial function and altering the functions of adiponectin and high-density lipoproteins (HDLs). Adiponectin is an adipokine involved in regulating energy metabolism and body composition. Serum adiponectin levels are reduced in obese individuals and negatively correlate with chronic sub-clinical inflammatory markers. HDLs are a heterogeneous and complex class of lipoproteins that can be dysfunctional in obesity. Adiponectin and HDLs are strictly interdependent, and the maintenance of their interplay is essential for vascular function.
  • 872
  • 16 Jun 2022
Topic Review
Delta and Lambda Variants of SARS-CoV-2
The high transmissibility of Delta and Lambda variants has raised the need to determine the reason for the infectivity of these variants. Since the Delta variant first emerged in India in June 2020, the global incidence of the Delta variant has made it a VOC. The Delta variant is 60% more infectious than the original Wuhan SARS-CoV-2 strain. Similarly, Lambda, a VOI, was first reported in Peru in December, 2020 and currently, its diverse mutations and increased frequency in over 29 countries has raised more attention.
  • 870
  • 23 Nov 2021
Topic Review
Traumatic Spinal Cord Injury
Traumatic spinal cord injury (SCI) is one of the most devastating diseases and results in severe motor and sensory dysfunction below the level of injury.
  • 868
  • 10 Aug 2021
Topic Review
NF-κB in Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy that relies on highly heterogeneous cytogenetic alterations. Although in the last few years new agents have been developed for AML treatment, the overall survival prospects for AML patients are still gloomy and new therapeutic options are still urgently needed. Constitutive NF-κB activation has been reported in around 40% of AML patients, where it sustains AML cell survival and chemoresistance. Given the central role of NF-κB in AML, targeting the NF-κB pathway represents an attractive strategy to treat AML.
  • 868
  • 08 Aug 2022
Topic Review
HCMV Latency
Human cytomegalovirus (HCMV) establishes both latent (where the virus is maintained in an absence of the production of infectious virions) and lytic (during primary infection and reactivation) phases of infection. The study of latency has been historically more difficult to study than that of lytic infection due to the relative quiescence of the virus in host cells and the limited cell types that support HCMV latency. With the advent of engineered HCMV viruses which express fluorescent tags that enable latently infected cells to be detected and isolated, it has been possible to analyse latently infected cells in much greater detail. In this article, we review studies which have used such systems to analyse and interrogate the latency associated proteome. These have led to the identification of cellular proteins and pathways important for latency and, consequently, potential therapeutic intervention drugs based on a greater understanding of latent infection.
  • 867
  • 21 Nov 2020
Topic Review
Local Oscillatory Brain Dynamics
A number of studies have focused on brain dynamics underlying mind wandering (MW) states in healthy people. However, there is limited understanding of how the oscillatory dynamics accompanying MW states and task-focused states are characterized in clinical populations.
  • 867
  • 29 Jul 2021
Topic Review
COVID-19 Infection in Children
A descriptive synthesis was performed to evaluate recent insights and the effectiveness of therapies for SARS-CoV-2 infection in children, infants and pregnant subjects. Results: Insufficient data are available regarding the relationship between COVID-19 and the clinical risk of spontaneous abortion and premature foetus death. A decrease in the incidence of COVID-19 could be correlated to a minor expression of ACE2 in childrens’ lungs.
  • 867
  • 23 Sep 2021
Topic Review
Microglial Responses to Stress-Induced Depression
Growing evidence suggests that microglial inflammatory activation is crucial in psychiatric disorders, including major depressive disorder (MDD). Chronic exposure to stressful stimuli, a significant risk factor for MDD, has been associated with the activation of peripheral and central immune cells, leading to inflammation. The aim is to discuss microglial responses to stress-induced depression comprehensively. Animal models used in preclinical studies of depression often utilize stressors to induce pathology similar to depression. These studies offer compelling evidence of microglial inflammatory activation, resulting in neuropathology and depressive-like behavior.
  • 867
  • 12 Jun 2023
Topic Review
FAK Signaling in Rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of children and adolescents. The fusion-positive (FP)-RMS variant expressing chimeric oncoproteins such as PAX3-FOXO1 and PAX7-FOXO1 is at high risk. The fusion negative subgroup, FN-RMS, has a good prognosis when non-metastatic. Despite a multimodal therapeutic approach, FP-RMS and metastatic FN-RMS often show a dismal prognosis with 5-year survival of less than 30%. Therefore, novel targets need to be discovered to develop therapies that halt tumor progression, reducing long-term side effects in young patients. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that regulates focal contacts at the cellular edges. It plays a role in cell motility, survival, and proliferation in response to integrin and growth factor receptors’ activation. FAK is often dysregulated in cancer, being upregulated and/or overactivated in several adult and pediatric tumor types. In RMS, both in vitro and preclinical studies point to a role of FAK in tumor cell motility/invasion and proliferation, which is inhibited by FAK inhibitors.
  • 864
  • 11 Mar 2021
Topic Review
Immune-Related miRNAs
MicroRNAs (miRNAs) are small non-coding regulatory RNA family that play pivotal roles in physiological and pathological conditions, including immune response. Immune-related miRNAs might on one side trigger the innate and adaptive immune response and regulate the expression of immune cells. On the other side, miRNAs can be diferentially expressed due to activated immune cells. All of this makes them valuable promising diagnostic, prognostic and predicative markers as well as potential therapeutic targets.
  • 864
  • 13 Sep 2021
Topic Review
α Cell in Diabetes Pathogenesis
The involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon’s secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans’ islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (β) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to β cell mass loss. Other abnormalities like α cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (KATP) opening have also been linked to glucagon hypersecretion. 
  • 855
  • 27 Oct 2021
Topic Review
Extracellular Vesicles as Biomarkers for Parkinson’s Disease
Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder, characterized by the misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies and the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The urge for an early diagnosis biomarker comes from the fact that clinical manifestations of PD are estimated to appear once the substantia nigra has deteriorated and there has been a reduction of the dopamine levels from the striatum. Extracellular vesicles (EVs) play an important role in the pathogenesis of neuro-degenerative diseases as PD. 
  • 854
  • 19 Oct 2022
Topic Review
Genes Associated with Atopic Dermatitis
Atopic dermatitis and abnormalities in tooth development (including hypomineralization, hypodontia and microdontia) have been observed to co-occur in some patients. A common pathogenesis pathway that involves genes and protein interactions has been hypothesized.
  • 851
  • 03 Apr 2023
Topic Review
Extra-mammary Paget’s Disease
Extramammary Paget disease (EMPD) was first described by Crocker in 1889 in a man affected from bladder carcinoma and presented with an eczematous lesion involving the penoscrotal region, that was diagnosed as Paget disease in an extramammary site. Subsequently EMPD has been reported involving more frequently the external female genitalia and less commonly, the perianal/perineal region, groin, axilla, umbilicus, eyelids, and also external ear canal. EMPD has been defined by World Health Organization (WHO) as an intraepithelial neoplasm of epithelial origin expressing apocrine or eccrine glandular-like features and characterized by distinctive large cells with prominent cytoplasm, referred to as Paget cells’.
  • 849
  • 22 Dec 2020
Topic Review
Diagnosis of Retroperitoneal Sarcoma
Soft tissue sarcomas (STS) are an uncommon and biologically heterogeneous group of tumors arising from mesenchymal cells. The incidence is estimated at five cases per 100,000 people per year. Retroperitoneal sarcomas (RPS) account for 10–15% of all STS, and their management depends on their anatomical characteristics and histotype. Due to their very low incidence, it is recommended that RPS be treated in reference centers and evaluated by an experienced multidisciplinary team (MDT). In Spain, the Spanish Group for Research in Sarcomas (GEIS) brings together experts from various specialties to promote research on sarcomas and improve treatment results.
  • 849
  • 25 Sep 2023
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