No abstract

While systemic immuno-oncology therapies have shown remarkable success, only a limited subset of patients benefit from them. The Click Activated Protodrugs Against Cancer (CAPAC) platform is a click chemistry-based approach that activates cancer drugs at a specific tumor with minimal systemic toxicity. The CAPAC Platform is agnostic to tumor characteristics that can vary across patients and hence applicable to several types of tumors. The benefits of SQ3370 (lead candidate of CAPAC) are described to achieve systemic anti-tumor responses in mice bearing two tumors. SQ3370 consists of a biopolymer, injected in a single lesion, followed by systemic doses of an attenuated protodrug of doxorubicin (Dox). SQ3370 is well-tolerated at 5.9-times the maximum dose of conventional Dox, increased survival by 63% and induces a systemic anti-tumor response against injected and non-injected lesions. The sustained anti-tumor response also correlates with immune activation measured at both lesions. SQ3370 can potentially benefit patients with micro-metastatic lesions.

The Click Activated Protodrugs Against Cancer (CAPAC) platform uses click chemistry to activate cytotoxic drugs directly at a target site with minimal toxicity, overcoming limitations of conventional chemotherapy and traditional targeted therapies.

Remarkable advances in biomedical research have led to the generation of large amounts of data. Using artificial intelligence, it has become possible to extract meaningful information from large volumes of data, in a shorter frame of time, with very less human interference. In effect, convolutional neural networks (a deep learning method) have been taught to recognize pathological lesions from images. Diabetes has high morbidity, with millions of people who need to be screened for diabetic retinopathy (DR). Deep neural networks offer a great advantage of screening for DR from retinal images, in improved identification of DR lesions and risk factors for diseases, with high accuracy and reliability. This review aims to compare the current evidences on various deep learning models for diagnosis of diabetic retinopathy (DR).

Keratoconus was the leading indication for keratoplasty in the West of Scotland. Both anterior LK and endothelial keratoplasty seemed to show an emerging trend as the procedures of choice for dealing with anterior and posterior corneal pathologies, respectively.

The LANDMark baseline findings confirm a reduction in corneal sensitivity only in Type 1 patients with neuropathy. However, corneal nerve fibre length is reduced in Type 1 patients without neuropathy with an even greater deficit in Type 1 patients with neuropathy.

Systemic administration of antibiotics can cause severe side-effects such as liver and kidney toxicity, destruction of healthy gut bacteria, as well as multidrug resistance. Here, we present a bio-orthogonal chemistry-based strategy toward local prodrug concentration and activation. The strategy is based on the inverse electron-demand Diels–Alder chemistry between trans-cyclooctene and tetrazine and involves a biomaterial that can concentrate and activate multiple doses of systemic antibiotic therapy prodrugs at a local site. We demonstrate that a biomaterial, consisting of alginate hydrogel modified with tetrazine, is efficient at activating multiple doses of prodrugs of vancomycin and daptomycin in vitro as well as in vivo. These results support a drug delivery process that is independent of endogenous environmental markers. This approach is expected to improve therapeutic efficacy with decreased side-effects of antibiotics against bacterial infections. The platform has a wide scope of possible applications such as wound healing, and cancer and immunotherapy.

PURPOSE.We report the 4-year incidence, progression, and risk factors of cataract subtypes in type 2 diabetes. METHODS.A total of 779 subjects completed baseline and 4-year follow-up.RESULTS. The incidences of nuclear opalescence (NO), nuclear color (NC), cortical cataract (CC), and posterior subcapsular cataract (PSC) were 70%, 55.2%, 25.7%, and 7.3%, respectively. One-step progressions of NO, NC, CC, and PSC were 14.3%, 16.1%, 8.8%, and 8.1%, respectively, and two-step or more progressions were 5.0%, 6.0%, 0.8%, and 6.0%, respectively. Incident NO was seen in patients 50 to 59 (odds ratio [OR] ¼ 3.3), NC in those 50 to 59 (OR ¼ 2.7) and 60 to 69 (OR ¼ 3.9), and CC in those 60 to 69 (OR ¼ 3.3) years old. A lower hemoglobin A 1c (HbA 1c ; OR ¼ 0.7), longer diabetes duration (OR ¼ 1.1), and hyperopia (OR ¼ 4.0) were associated with incident PSC. Women (OR ¼ 1.7) and patients with higher total cholesterol (OR ¼ 1.3) at baseline showed one-step NO progression. Patients 60 to 69 (OR ¼ 2.8) and ‡70 (OR ¼ 3.8) years old showed one-step NC progression, while those 60 to 69 years old showed one-step CC progression (OR ¼ 6.3). A lower HbA 1c (OR ¼ 0.3) was associated with one-step PSC progression. A higher low-density lipoprotein (OR ¼ 1.6) was associated with two-step or more NO progression. Patients 60 to 69 years old (OR ¼ 6.7) had a greater risk, while those with hyperopia at baseline (OR ¼ 0.2) had lower risk of two-step or more NC progression. Patients 40 to 49 years old constituted the reference group for all.CONCLUSIONS. The 4-year cumulative incidence of cataract is higher than that of progression. Greater age is a risk factor for incidence and progression of most types of cataract.