Are Expert Patients an Untapped Resource for ART Provision in Sub-Saharan Africa?

Since the introduction of antiretroviral treatment, HIV/AIDS can be framed as a chronic lifelong condition, requiring lifelong adherence to medication. Reinforcement of self-management through information, acquisition of problem solving skills, motivation, and peer support is expected to allow PLWHA to become involved as expert patients in the care management and to decrease the dependency on scarce skilled medical staff. We developed a conceptual framework to analyse how PLWHA can become expert patients and performed a literature review on involvement of PLWHA as expert patients in ART provision in Sub-Saharan Africa. This paper revealed two published examples: one on trained PLWHA in Kenya and another on self-formed peer groups in Mozambique. Both programs fit the concept of the expert patient and describe how community-embedded ART programs can be effective and improve the accessibility and affordability of ART. Using their day-to-day experience of living with HIV, expert patients are able to provide better fitting solutions to practical and psychosocial barriers to adherence. There is a need for careful design of models in which expert patients are involved in essential care functions, capacitated, and empowered to manage their condition and support fellow peers, as an untapped resource to control HIV/AIDS

Lewis A glycans are present on proteins involved in cell wall biosynthesis and appear evolutionarily conserved amongnatural Arabidopsis thaliana accessions

N-glycosylation is a highly abundant protein modification present in all domains of life. Terminal sugar residues on complex-type N-glycans mediate various crucial biological processes in mammals such as cell-cell recognition or protein-ligand interactions. In plants, the Lewis A trisaccharide constitutes the only known outer-chain elongation of complex N-glycans. Lewis A containing complex N-glycans appear evolutionary conserved, having been identified in all plant species analyzed so far. Despite their ubiquitous occurrence, the biological function of this complex N-glycan modification is currently unknown. Here, we report the identification of Lewis A bearing glycoproteins from three different plant species: Arabidopsis thaliana, Nicotiana benthamiana, and Oryza sativa. Affinity purification via the JIM84 antibody, directed against Lewis A structures on complex plant N-glycans, was used to enrich Lewis A bearing glycoproteins, which were subsequently identified via nano-LC-MS. Selected identified proteins were recombinantly expressed and the presence of Lewis A confirmed via immunoblotting and site-specific N-glycan analysis. While the proteins identified in O. sativa are associated with diverse functions, proteins from A. thaliana and N. benthamiana are mainly involved in cell wall biosynthesis. However, a Lewis A-deficient mutant line of A. thaliana showed no change in abundance of cell wall constituents such as cellulose or lignin. Furthermore, we investigated the presence of Lewis A structures in selected accessions from the 1001 genome database containing amino acid variations in the enzymes required for Lewis A biosynthesis. Besides one relict line showing no detectable levels of Lewis A, the modification was present in all other tested accessions. The data provided here comprises the so far first attempt at identifying Lewis A bearing glycoproteins across different species and will help to shed more light on the role of Lewis A structures in plants

Rapamycin-dependent delocalization as a novel tool to reveal protein-protein interactions in plants

Identifying protein-protein interactions (PPI) is crucial to understand any type of biological process. Many PPI tools are available, yet only some function within the context of a plant cell. Narrowing down even further, only few PPI tools allow visualizing higher order interactions. Here, we present a novel and conditional in vivo PPI tool for plant research. Knocksideways in plants (KSP) uses the ability of rapamycin to alter the localization of a bait protein and its interactors via the heterodimerization of FKBP and FRB domains. KSP is inherently free from many limitations, which other PPI systems hold. It is an in vivo tool, it is flexible concerning the orientation of protein tagging as long as this does not interfere with the interaction and it is compatible with a broad range of fluorophores. KSP is also a conditional tool and therefore does not require additional controls. The interactions can be quantified and in high throughput by the scripts that we provide. Finally, we demonstrate that KSP can visualize higher-order interactions. It is therefore a versatile tool, complementing the PPI methods field with unique characteristics and applications

Adapting a community-based ART delivery model to the patients’ needs: a mixed methods research in Tete, Mozambique

BACKGROUND: To improve retention in antiretroviral therapy (ART), lessons learned from chronic disease care were applied to HIV care, providing more responsibilities to patients in the care of their chronic disease. In Tete - Mozambique, patients stable on ART participate in the ART provision and peer support through Community ART Groups (CAG). This article analyses the evolution of the CAG-model during its implementation process. METHODS: A mixed method approach was used, triangulating qualitative and quantitative findings. The qualitative data were collected through semi-structured focus groups discussions and in-depth interviews. An inductive qualitative content analysis was applied to condense and categorise the data in broader themes. Health outcomes, patients’ and groups’ characteristics were calculated using routine collected data. We applied an ‘input – process – output’ pathway to compare the initial planned activities with the current findings. RESULTS: Input wise, the counsellors were considered key to form and monitor the groups. In the process, the main modifications found were the progressive adaptations of the daily CAG functioning and the eligibility criteria according to the patients’ needs. Beside the anticipated outputs, i.e. cost and time saving benefits and improved treatment outcomes, the model offered a mutual adherence support and protective environment to the members. The active patient involvement in several health activities in the clinics and the community resulted in a better HIV awareness, decreased stigma, improved health seeking behaviour and better quality of care. CONCLUSIONS: Over the past four years, the modifications in the CAG-model contributed to a patient empowerment and better treatment outcomes. One of the main outstanding questions is how this model will evolve in the future. Close monitoring is essential to ensure quality of care and to maintain the core objective of the CAG-model ‘facilitating access to ART care’ in a cost and time saving manner

New opportunities and insights into Papaver selfincompatibility by imaging engineered Arabidopsis pollen

Pollen tube growth is essential for plant reproduction. Their rapid extension using polarized tip growth provides an exciting system for studying this specialized type of growth. Self-incompatibility (SI) is a genetically controlled mechanism to prevent self-fertilization. Mechanistically, one of the best-studied SI systems is that of Papaver rhoeas (poppy). This utilizes two S-determinants: stigma-expressed PrsS and pollen-expressed PrpS. Interaction of cognate PrpS–PrsS triggers a signalling network, causing rapid growth arrest and programmed cell death (PCD) in incompatible pollen. We previously demonstrated that transgenic Arabidopsis thaliana pollen expressing PrpS–green fluorescent protein (GFP) can respond to Papaver PrsS with remarkably similar responses to those observed in incompatible Papaver pollen. Here we describe recent advances using these transgenic plants combined with genetically encoded fluorescent probes to monitor SI-induced cellular alterations, including cytosolic calcium, pH, the actin cytoskeleton, clathrin-mediated endocytosis (CME), and the vacuole. This approach has allowed us to study the SI response in depth, using multiparameter live-cell imaging approaches that were not possible in Papaver. This lays the foundations for new opportunities to elucidate key mechanisms involved in SI. Here we establish that CME is disrupted in self-incompatible pollen. Moreover, we reveal new detailed information about F-actin remodelling in pollen tubes after SI

Overcoming I/O bottleneck in superconducting quantum computing: multiplexed qubit control with ultra-low-power, base-temperature cryo-CMOS multiplexer

Large-scale superconducting quantum computing systems entail high-fidelity control and readout of large numbers of qubits at millikelvin temperatures, resulting in a massive input-output bottleneck. Cryo-electronics, based on complementary metal-oxide-semiconductor (CMOS) technology, may offer a scalable and versatile solution to overcome this bottleneck. However, detrimental effects due to cross-coupling between the electronic and thermal noise generated during cryo-electronics operation and the qubits need to be avoided. Here we present an ultra-low power radio-frequency (RF) multiplexing cryo-electronics solution operating below 15 mK that allows for control and interfacing of superconducting qubits with minimal cross-coupling. We benchmark its performance by interfacing it with a superconducting qubit and observe that the qubit's relaxation times ($T_1$) are unaffected, while the coherence times ($T_2$) are only minimally affected in both static and dynamic operation. Using the multiplexer, single qubit gate fidelities above 99.9%, i.e., well above the threshold for surface-code based quantum error-correction, can be achieved with appropriate thermal filtering. In addition, we demonstrate the capability of time-division-multiplexed qubit control by dynamically windowing calibrated qubit control pulses. Our results show that cryo-CMOS multiplexers could be used to significantly reduce the wiring resources for large-scale qubit device characterization, large-scale quantum processor control and quantum error correction protocols.Comment: 16+6 pages, 4+1+5 figures, 1 tabl

Avelumab in paediatric patients with refractory or relapsed solid tumours: dose-escalation results from an open-label, single-arm, phase 1/2 trial

Background: We report dose-escalation results from an open-label, phase 1/2 trial evaluating avelumab (anti-PD-L1) in paediatric patients with refractory/relapsed solid tumours. Methods: In phase 1, patients aged \u3c 18 years with solid (including central nervous system [CNS]) tumours for which standard therapy did not exist or had failed were enrolled in sequential cohorts of 3–6 patients. Patients received avelumab 10 or 20 mg/kg intravenously every 2 weeks. Primary endpoints were dose-limiting toxicities (DLTs) and grade ≥ 3 treatment-emergent adverse events (AEs). Results: At data cut-off (27 July 2021), 21 patients aged 3–17 years had received avelumab 10 mg/kg (n = 6) or 20 mg/kg (n = 15). One patient had three events that were classified as a DLT (fatigue with hemiparesis and muscular weakness associated with pseudoprogression; 20 mg/kg cohort). Grade ≥ 3 AEs occurred in five (83%) and 11 (73%) patients in the 10 and 20 mg/kg cohorts, respectively, and were treatment-related in one patient (7%; grade 3 [DLT]) in the 20 mg/kg cohort. Avelumab exposure in paediatric patients receiving 20 mg/kg dosing, but not 10 mg/kg, was comparable or higher compared with approved adult dosing (10 mg/kg or 800 mg flat dose). No objective responses were observed. Four patients with CNS tumours (20 mg/kg cohort) achieved stable disease, which was ongoing in two patients with astrocytoma at cut-off (for 24.7 and 30.3 months). Conclusion: In paediatric patients with refractory/relapsed solid tumours, avelumab monotherapy showed a safety profile consistent with previous adult studies, but clinical benefits were limited