Smart Nanocarriers as an Emerging Platform for Cancer Therapy: A Review

Cancer is a group of disorders characterized by uncontrolled cell growth that affects around 11 million people each year globally. Nanocarrier-based systems are extensively used in cancer imaging, diagnostics as well as therapeutics; owing to their promising features and potential to augment therapeutic efficacy. The focal point of research remains to develop new-fangled smart nanocarriers that can selectively respond to cancer-specific conditions and deliver medications to target cells efficiently. Nanocarriers deliver loaded therapeutic cargos to the tumour site either in a passive or active mode, with the least drug elimination from the drug delivery systems. This review chiefly focuses on current advances allied to smart nanocarriers such as dendrimers, liposomes, mesoporous silica nanoparticles, quantum dots, micelles, superparamagnetic iron-oxide nanoparticles, gold nanoparticles and carbon nanotubes, to list a few. Exhaustive discussion on crucial topics like drug targeting, surface decorated smart-nanocarriers and stimuli-responsive cancer nanotherapeutics responding to temperature, enzyme, pH and redox stimuli have been covered.

Leg length discrepancy: A systematic review on the validity and reliability of clinical assessments and imaging diagnostics used in clinical practice

Background A variety of assessments to determine leg length discrepancy (LLD) is used in clinical practice and evidence about validity and reliability may differ. Objective The objective of this systematic review was to identify and describe the validity and reliability of different assessments and imaging diagnostics for the determination of LLD. Materials and methods The review was conducted following the recommendations of Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The databases Medline (PubMed) and Index to Chiropractic Literature were systematically searched. Studies regarding clinical assessments and imaging diagnostics for the diagnosis of LLD, which reported the clinimetric properties for assessment of LLD, were included and screened for methodological quality using the Quality Assessment of Studies of Diagnostic Accuracy (QUADAS-2) tool for validity studies and the Quality Appraisal of Diagnostic Reliability (QAREL) tool for reliability studies. Results Thirty-seven articles on clinical assessments and 15 studies on imaging diagnostics met the eligibility criteria. Thirteen studies on the validity of clinical assessments and six studies on the validity of imaging diagnostics had a low risk of bias and low concerns regarding applicability for all domains. One study on the reliability of clinical assessments and one study on the reliability of imaging diagnostics had a low risk of bias. Main limitations were, that an analysis of sensitivity and specificity was only performed in a few studies and that a valid reference standard was lacking in numerous studies on clinical assessments. Conclusions For the clinical assessment of LLD, the block test appears to be the most useful method. Full-length standing anteroposterior radiography seems to be the most valid and reliable method and may be used as global reference standard to measure the anatomic LLD when comparing clinical methods and imaging diagnostics.

Overview of Epidemiology and Management of Undescended Testis (Cryptorchidism)

Cryptorchidism (undescended testis, maldescendus testis) is a disorder in which one or together testes miscarry to slope into the bottommost of the scrotum. The study aimed to summarize the updated evidence regards, epidemiology, etiology, classification, diagnosis, and treatments of Cryptorchidism or undescended testis. Several causes can result in developing cryptorchidism. Disruption of any phase of testicular prolapse due to genetic hormonal, structural, ecological, or social issues can lead to cryptorchidism. The diagnosis of undescended testes is clinical. The test should be performed by an experienced person and should always be performed using a two-way technique. In some cases, imaging diagnostics for cryptorchidism may be helpful. The rationale for treating cryptorchidism is to reduce the risk of its long-term consequences. Current treatments for undescended testes include hormone therapy, orchopexy, and surgical correction.

Evaluation of OIDx Histoplasma Urinary Antigen EIA

A sandwich enzyme immunoassay (EIA) for the detection of Histoplasma antigens (Ag) in urine, developed by Optimum Imaging Diagnostics (OIDx) was evaluated. A verification using a standardized reference panel of urine samples found sensitivity of 92%, specificity of 32% and accuracy of 51%. In this study, the OIDx Histoplasma urinary Ag EIA displayed high sensitivity, however, in non-histoplasmosis cases this EIA displayed false-positive results in 68% of specimens tested.

Programmably switching the NIR upconversion for orthogonal activation of photoacoustic imaging and on-demand phototherapy

Upconversion nanoparticles (UCNPs) based phototheranostics offer significant expectations for the personalized cancer medicine via integrating both modalities of imaging diagnostics and phototherapeutics. However, programmably controlling the photoactivation of imaging and therapy towards the accurate diagnosis with minimum side effects for on-demand therapy has remained challenging due to the lack of ideal switchable UCNPs agents. Herein, we demonstrate a facile strategy to simply switch the near infrared emission at 800 nm from rationally designed UCNPs by modulating the irradiation laser into pulse output. Through synthesis of the theranostic UCNPs-DI agent combining with a photosensitizer and a photoabsorbing agent assembled on the UCNPs, the orthogonal activation of in vivo photoacoustic imaging and photodynamic therapy was further achieved by simply altering the excitation modes from pulse to continuous-wave output upon a single 980-nm laser. Importantly, no obvious harmful effects during photoexcitation caused by reactive oxygen species (ROS) photooxidation and photohyperthermia were generated under imaging modality, which facilitates the long-term and real-time imaging-guidance for the subsequent phototherapy. This work provides a new facile approach for the orthogonal activation of imaging diagnostics and photodynamic therapeutics towards the target cancers.

Role of Peptides in Diagnostics

The specificity of a diagnostic assay depends upon the purity of the biomolecules used as a probe. To get specific and accurate information of a disease, the use of synthetic peptides in diagnostics have increased in the last few decades, because of their high purity profile and ability to get modified chemically. The discovered peptide probes are used either in imaging diagnostics or in non-imaging diagnostics. In non-imaging diagnostics, techniques such as Enzyme-Linked Immunosorbent Assay (ELISA), lateral flow devices (i.e., point-of-care testing), or microarray or LC-MS/MS are used for direct analysis of biofluids. Among all, peptide-based ELISA is considered to be the most preferred technology platform. Similarly, peptides can also be used as probes for imaging techniques, such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The role of radiolabeled peptides, such as somatostatin receptors, interleukin 2 receptor, prostate specific membrane antigen, αβ3 integrin receptor, gastrin-releasing peptide, chemokine receptor 4, and urokinase-type plasminogen receptor, are well established tools for targeted molecular imaging ortumor receptor imaging. Low molecular weight peptides allow a rapid clearance from the blood and result in favorable target-to-non-target ratios. It also displays a good tissue penetration and non-immunogenicity. The only drawback of using peptides is their potential low metabolic stability. In this review article, we have discussed and evaluated the role of peptides in imaging and non-imaging diagnostics. The most popular non-imaging and imaging diagnostic platforms are discussed, categorized, and ranked, as per their scientific contribution on PUBMED. Moreover, the applicability of peptide-based diagnostics in deadly diseases, mainly COVID-19 and cancer, is also discussed in detail.

Application of Carbon Nanoparticles in Oncology and Regenerative Medicine

Currently, carbon nanoparticles play a large role as carriers of various types of drugs, and also have applications in other fields of medicine, e.g., in tissue engineering, where they are used to reconstruct bone tissue. They also contribute to the early detection of cancer cells, and can act as markers in imaging diagnostics. Their antibacterial and anti-inflammatory properties are also known. This feature is particularly important in dental implantology, where various types of bacterial infections and implant rejection often occur. The search for newer and more effective treatments may lead to future use of nanoparticles on a large scale. In this work, the current state of knowledge on the possible use of nanotubes, nanodiamonds, and fullerenes in therapy is reviewed. Both advantages and disadvantages of the use of carbon nanoparticles in therapy and diagnostics have been indicated.

Federated Learning for Multi-Center Imaging Diagnostics: A Study in Cardiovascular Disease

Deep learning models can enable accurate and efficient disease diagnosis, but have thus far been hampered by the data scarcity present in the medical world. Automated diagnosis studies have been constrained by underpowered single-center datasets, and although some results have shown promise, their generalizability to other institutions remains questionable as the data heterogeneity between institutions is not taken into account. By allowing models to be trained in a distributed manner that preserves patients’ privacy, federated learning promises to alleviate these issues, by enabling diligent multi-center studies. We present the first federated learning study on the modality of cardiovascular magnetic resonance (CMR) and use four centers derived from subsets of the M&M and ACDC datasets, focusing on the diagnosis of hypertrophic cardiomyopathy (HCM). We adapt a 3D-CNN network pretrained on action recognition and explore two different ways of incorporating shape prior information to the model, and four different data augmentation setups , systematically analyzing their impact on the different collaborative learning choices. We show that despite the small size of data (180 subjects derived from four centers), the privacy preserving federated learning achieves promising results that are competitive with traditional centralized learning. We further find that federatively trained models exhibit increased robustness and are more sensitive to domain shift effects.