Cancer diagnostic service use in people with HIV in South Africa: a cross-sectional study.

Objective: The objective of this study was to map place of cancer diagnosis in relation to Human Immunodeficiency Virus (HIV) care centre among people with HIV (PWH) within South Africa (SA) using national laboratory database.

Design: We linked HIV and cancer laboratory data from 2004-2014 using supervised machine-learning algorithms. We performed a cross-sectional analysis comparing province where individuals accessed their HIV care versus where they had their cancer diagnosis.

Cohort profile: the South African HIV Cancer Match (SAM) Study, a national population-based cohort.

Purpose: The South African HIV Cancer Match (SAM) Study is a national cohort of people living with HIV (PLWH). It was created using probabilistic record linkages of routine laboratory records of PLWH retrieved by National Health Laboratory Services (NHLS) and cancer data from the National Cancer Registry. The SAM Study aims to assess the spectrum and risk of cancer in PLWH in the context of the evolving South African HIV epidemic.

Cancer risk in adolescents and young adults living with HIV in South Africa: a nationwide cohort study.

Background: Literature on cancer in adolescents and young adults (AYA; aged 15-24 years) living with HIV is scarce. We studied cancer incidence in AYA living with HIV in South Africa between 2004 and 2014.

Methods: In this nationwide cohort study, we included individuals between 15 and 24 years old who had at least two HIV-related laboratory measurements on separate days between Jan 1, 2004, and Dec 31, 2014, recorded in the National Health Laboratory Service database.

Spatiotemporal modelling and mapping of cervical cancer incidence among HIV positive women in South Africa: a nationwide study.

Background: Disparities in invasive cervical cancer (ICC) incidence exist globally, particularly in HIV positive women who are at elevated risk compared to HIV negative women. We aimed to determine the spatial, temporal, and spatiotemporal incidence of ICC and the potential risk factors among HIV positive women in South Africa.

Methods: We included ICC cases in women diagnosed with HIV from the South African HIV cancer match study during 2004-2014.

Immunodeficiency and Cancer in 3.5 Million People Living With Human Immunodeficiency Virus (HIV): The South African HIV Cancer Match Study.

Background: We analyzed associations between immunodeficiency and cancer incidence in a nationwide cohort of people living with human immunodeficiency virus (HIV; PLWH) in South Africa.

Methods: We used data from the South African HIV Cancer Match Study built on HIV-related laboratory measurements from the National Health Laboratory Services and cancer records from the National Cancer Registry. We evaluated associations between time-updated CD4 cell count and cancer incidence rates using Cox proportional hazards models.

mTOR Blockade by Rapamycin in Spondyloarthritis: Impact on Inflammation and New Bone Formation and .

Spondyloarthritis (SpA) is characterized by inflammation, articular bone erosions and pathologic new bone formation. Targeting TNFα or IL-17A with current available therapies reduces inflammation in SpA, however, treatment of the bone pathology in SpA remains an unmet clinical need. Activation of the mammalian target Of rapamycin (mTOR) promotes IL-17A expression and osteogenesis.

Highly Efficient Mono-Functionalization of Knob-in-Hole Antibodies with Strain-Promoted Click Chemistry.

Knob-in-hole antibodies can be utilized to introduce a single tag for chemo-enzymatic functionalization. By either introducing a single C-terminal sortase tag (sortase-tag expressed protein ligation) or tyrosine tag (GY), mono-functionalization of the monoclonal antibody trastuzumab was achieved rapidly and in high yields. This method was applied to selectively and efficiently introduce a single fluorescent tag, cytokine or single-chain variable fragment, as well as produce clean homo dimers of trastuzumab.

A Chemo-enzymatically Linked Bispecific Antibody Retargets T Cells to a Sialylated Epitope on CD43 in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a high-risk disease with a poor prognosis, particularly in elderly patients. Because current AML treatment relies primarily on untargeted therapies with severe side effects that limit patient eligibility, identification of novel therapeutic AML targets is highly desired. We recently described AT1413, an antibody produced by donor B cells of a patient with AML cured after allogeneic hematopoietic stem cell transplantation.

Preparation of bispecific antibody-protein adducts by site-specific chemo-enzymatic conjugation.

Historically, bispecific antibodies have been constructed through the genetic fusion of additional binding domains to the constant domains of the antibody heavy- or light chains. We present an alternative method for the introduction of additional functional domains to an antibody: site-specific chemo-enzymatic conjugation. This method relies on the combination of site-specific transpeptidases and bioorthogonal chemistry.

Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation of Protein-Protein Interactions.

The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein that controls signaling at synapses in the brain through interactions of its PDZ domains with the C-termini of receptors, ion channels, and enzymes. PSD-95 is highly regulated by phosphorylation. To explore the effect of phosphorylation on PSD-95, we used semisynthetic strategies to introduce phosphorylated amino acids at four positions within the PDZ domains and examined the effects on interactions with a large set of binding partners.

Inducible, Site-Specific Protein Labeling by Tyrosine Oxidation-Strain-Promoted (4 + 2) Cycloaddition.

Genetically encoded tyrosine (Y-tag) can be utilized as a latent anchor for inducible and site-selective conjugation. Upon oxidation of tyrosine with mushroom tyrosinase, strain-promoted cycloaddition (SPOCQ) of the resulting 1,2-quinone with various bicyclo[6.1.