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Topic Review
Primary Sclerosing Cholangitis-Associated Cholangiocarcinoma
Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC), accounting for 2–8% of cases and being the leading cause of death in these patients. The majority of PSC-associated CCAs (PSC-CCA) develop within the first few years after PSC diagnosis. Older age and male sex, as well as concomitant inflammatory bowel disease (IBD) or high-grade biliary stenosis, are some of the most relevant risk factors. PSC-CCA pathogenesis is characterised by peculiar molecular and genetic features, being a distinct disease from the novo CCA. There has been a significant push to develop innovative strategies for PSC-CCA early diagnosis and surveillance. 
  • 302
  • 23 Oct 2023
Topic Review
Physical Deactivation Oral Immunotherapy Methods for Food Allergens
Food allergies represent a serious health concern and, since the 1990s, they have risen gradually in high-income countries. Deactivation rather than degradation should be the way of attenuating the immune response. Methods involve both physical and chemo-enzymatic routes.
  • 234
  • 23 Oct 2023
Topic Review
Sex Differences in Efficacy of ICIs in NSCLC
Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for metastatic non-small cell lung cancer (NSCLC) patients (IB-IIIA) with no targetable driver mutations. Although genetic and physiological factors could suggest a priori differences in response to ICIs regarding sex. It is well established that women have a more proficient immune system; thus, a higher immune editing level is needed to develop metastatic disease, which could explain their better responses in the early phases of disease. Furthermore, the encouraging results observed for metastatic disease have promoted the use of ICIs as neoadjuvant treatments.
  • 257
  • 23 Oct 2023
Topic Review
Emerging Interventions for Autosomal Recessive ABCA4-Associated Stargardt Disease
Autosomal recessive Stargardt disease (STGD1) is an inherited retinal degenerative disease associated with a mutated ATP-binding cassette, subfamily A, member 4 (ABCA4) gene. STGD1 is the most common form of juvenile macular degeneration with onset in late childhood to early or middle adulthood and causes progressive, irreversible visual impairment and blindness. 
  • 186
  • 23 Oct 2023
Topic Review
Antibody–Drug Conjugate for Cancer Treatment
Cancer, also known as malignant tumour or neoplasm, is a leading cause of death worldwide. One distinct feature from normal cells is that cancerous cells often overexpress protein on the cell membrane—for instance, the overexpression of human epidermal growth factor receptor 2. The expression of a specific protein on the cancerous cell surface acts as a marker that differentiates the normal cell and facilitates the recognition of cancerous cells. An emerging anticancer treatment, Antibody–Drug Conjugates (ADCs), utilises this unique feature to kill cancerous cells. ADCs consist of an antibody linked with a cytotoxic payload, mainly targeting the antigen found on cancerous cells. This design can increase the specificity in delivering the cytotoxin to the drug target, thus increasing the drug efficacy and reducing the side effect of cancer treatment due to off-target toxicities. 
  • 337
  • 23 Oct 2023
Topic Review
Characterization, Therapy and Management of Alport Syndrome
Alport syndrome (AS) is a rare genetic disorder categorized by the progressive loss of kidney function, sensorineural hearing loss and eye abnormalities. It occurs due to mutations in three genes that encode for the alpha chains of type IV collagen. Globally, the disease is classified based on the pattern of inheritance into X-linked AS (XLAS), which is caused by pathogenic variants in COL4A5, representing 80% of AS. Autosomal recessive AS (ARAS), caused by mutations in either COL4A3 or COL4A4, represents 15% of AS. Autosomal dominant AS (ADAS) is rare and has been recorded in 5% of all cases due to mutations in COL4A3 or COL4A4. 
  • 372
  • 23 Oct 2023
Topic Review
Oxidative Stress as Regulatory Checkpoint in Antiphospholipid Autoantibodies
Oxidative stress is a well-known hallmark of Antiphospholipid Antibody Syndrome (APS), a systemic autoimmune disease characterized by arterial and venous thrombosis and/or pregnancy morbidity. Oxidative stress may affect various signaling pathways and biological processes, promoting dysfunctional immune responses and inflammation, inducing apoptosis, deregulating autophagy and impairing mitochondrial function. The chronic oxidative stress and the dysregulation of the immune system leads to the loss of tolerance, which drives autoantibody production and inflammation with the development of endothelial dysfunction. In particular, anti-phospholipid antibodies (aPL), which target phospholipids and/or phospholipid binding proteins, mainly β-glycoprotein I (β-GPI), play a functional role in the cell signal transduction pathway(s), thus contributing to oxidative stress and thrombotic events. An oxidation–antioxidant imbalance may be detected in the blood of patients with APS as a reflection of disease progression. 
  • 194
  • 23 Oct 2023
Topic Review
De Novo Metastatic Prostate Cancer Treatment
De novo metastatic hormone-sensitive prostate cancer usually has a dismal prognosis, which has slightly improved thanks to the introduction of new hormonal agents and chemotherapy combined with androgen deprivation therapy from the first-line setting. The randomized clinical trials that have furnished the current therapeutic options stratified patients according to clinical criteria that do not necessarily reflect the biological rationale of the chosen therapy. With the accumulation of data on genomic features and transcriptomic profiling, several ongoing clinical trials are investigating new therapeutic approaches and the efficacy of a biomarker-guided treatment with the aim of defining a personalized treatment for de novo metastatic hormone-sensitive prostate cancer.
  • 151
  • 23 Oct 2023
Topic Review
Revascularization and Left Ventricular Dysfunction for ICD Eligibility
Common triggers for sudden cardiac death (SCD) are transient ischemia, hemodynamic fluctuations, neurocardiovascular influences, and environmental factors. SCD occurs rapidly when sinus rhythm degenerates into ventricular tachycardia (VT) and/or ventricular fibrillation (VF), followed by asystole. Such progressive worsening of the cardiac rhythm is in most cases observed in the setting of ischemic heart disease and often associated with advanced left ventricular (LV) impairment. Revascularization prevents negative outcomes including SCD and heart failure (HF) due to LV dysfunction (LVD). The implantable cardioverter–defibrillator (ICD) on top of medical therapy is superior to antiarrhythmic drugs for patients with LVD and VT/VF. The beneficial effects of ICD have been demonstrated in primary prevention of SCD as well.
  • 330
  • 23 Oct 2023
Topic Review
Intraoperative Imaging in Hepatopancreatobiliary Surgery
Hepatopancreatobiliary surgery belongs to one of the most complex fields of general surgery. An intricate and vital anatomy is accompanied by difficult distinctions of tumors from fibrosis and inflammation; the identification of precise tumor margins; or small, even disappearing, lesions on currently available imaging. The routine implementation of ultrasound use shifted the possibilities in the operating room, yet more precision is necessary to achieve negative resection margins. Modalities utilizing fluorescent-compatible dyes have proven their role in hepatopancreatobiliary surgery, although this is not yet a routine practice, as there are many limitations. Modalities, such as photoacoustic imaging or 3D holograms, are emerging but are mostly limited to preclinical settings. There is a need to identify and develop an ideal contrast agent capable of differentiating between malignant and benign tissue and to report on the prognostic benefits of implemented intraoperative imaging in order to navigate clinical translation.
  • 259
  • 23 Oct 2023
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