The ripening behavior of blueberries (Vaccinium corymbosum) remains debated, with classifications ranging from climacteric to non-climacteric or atypical climacteric. While the role of ethylene in blueberry ripening has been primarily studied through postharvest ethephon treatments, its endogenous function and the presence of system II ethylene biosynthesis remain unclear. This study aimed to evaluate the role of ethylene in blueberry fruit ripening and determine the presence or absence of system II ethylene biosynthesis for fruit ripening classification. Highbush blueberries exhibited low ethylene emissions, which increased at the fruit coloring and pink stages, coinciding with an increase in the ethylene precursors S-adenosylmethionine and 1-aminocyclopropane-1-carboxylic acid, increased respiration rate, acidity loss, sugar accumulation, anthocyanin synthesis, and fruit pigmentation. Genome-wide analysis identified two putative ethylene biosynthetic genes, VcACS3 and VcACO6, which were expressed during ripening and functionally validated via transient overexpression in 'O'Neal' fruit. However, in planta and postharvest propylene treatment, which mimics the effects of ethylene, failed to induce autocatalytic ethylene biosynthesis across cultivars. Additionally, in planta and postharvest 1-methylcyclopropene treatment in all genotypes, and transient overexpression of Atetr1-1 in 'O'Neal' fruit, inhibited ripening without reducing ethylene emission. These findings indicate that while ethylene modulates blueberry ripening, its biosynthesis is not autocatalytically controlled. Thus, blueberries are best classified as non-climacteric fruit with ethylene-dependent ripening characteristics.
Accurate diagnostics are essential for disease control and elimination efforts. However, access to diagnostics for neglected tropical diseases (NTDs) is hindered by limited healthcare infrastructure in many NTD-endemic regions, as well as by reliance on time- and labor-intensive diagnostic methods, such as smear microscopy. New diagnostic tools that are portable, rapid, low-cost, and meet World Health Organization (WHO) sensitivity and specificity targets are urgently needed to accelerate NTD control and elimination programs. Here, we introduce the NTDscope, a portable microscopy platform that enables point-of-care imaging and automated detection of parasites and other pathogens in patient samples. The NTDscope builds on and extends the capabilities of the LoaScope, a device that turned the camera of a mobile phone into a microscope and used on-board image processing to automatically quantify Loa loa microfilariae burden in whole blood samples. The NTDscope replaces the mobile phone of the LoaScope with a system-on-module (SOM) that enables the integration of multiple imaging modalities in a single package designed to improve robustness and expand applications. In this work, we demonstrate the use of the NTDscope as a portable brightfield, darkfield, and fluorescence microscope for samples including microfilariae and helminth eggs. We also show that the device can be used to quantify molecular assays, such as a lateral flow test and a CRISPR-Cas13a-based assay. The ability to combine the diagnostic capabilities of conventional microscopy with molecular assays and machine learning in a single device could expand access to diagnostics for populations in NTD-endemic areas and beyond.
Introduction Healthcare delivery should be based on evidence-informed decisions in the clinical, public health, managerial and policy domains. Data are gathered at the point of care via routine health information systems (RHIS). The Paper-based Health Information Systems in Comprehensive Care (PHISICC) project shifted the paradigm from data collection to decision-making, especially decision-making at the point of care by the frontline health workers. We used a human-centred design (HCD) approach to re-design a RHIS that is responsive to the needs of frontline health workers.Methods The PHISICC research programme took place in Côte d’Ivoire, Mozambique and Nigeria and included the design and testing of a suite of paper-based RHIS tools. We report here the results of the HCD process. This was structured into three phases: (1) setup of co-creation group, (2) concept exploration and (3) detailed design phase.Results The concept exploration included a brainstorming session and produced ‘quick paper mock-ups’, such as ideas to follow-up patients’ healthcare. The output of this ‘concept workshop’ was a design hypothesis of the health information system. A follow-up workshop identified the healthcare areas to prioritise. The first round of design developed a version of several tools. The second round consisted of user testing in the three countries. Several iterations were implemented, incorporating health workers’ feedback. Tools were pilot-tested and then produced and distributed for use in a cluster randomised controlled trial.Conclusion The design phase of PHISICC combined HCD with clinical and public health domains. RHIS should be designed by qualified designers, content experts and users who focus on aiding decision-making of frontline health workers, applying a user-centred approach, from problem identification up to solution testing, multidisciplinarity, flexibility, teamwork and trust. We call for researchers, designers, healthcare providers, healthcare authorities and funding agencies to propose and pilot quality standards for the implementation and reporting of HCD in global health.
BACKGROUND:Trichuriasis is a neglected tropical disease that affects up to 500 million individuals and can cause considerable morbidity. For decades, trichuriasis was thought to be caused by one species of whipworm, Trichuris trichiura. The aim of this study was to investigate the origin of differences in response rates to the best available anthelmintic treatment for trichuriasis-a combination of albendazole and ivermectin-in Côte d'Ivoire by analysing the parasite population. METHODS:In this morphological, genomic, and genome-wide association study (GWAS) with drug sensitivity we used long-read and short-read sequencing approaches and assembled a high-quality reference genome of Trichuris incognita n sp isolated in a primary interventional study conducted in the Lagunes district of Côte d'Ivoire. Children aged 6-12 years were screened between July 14, 2022, and July 31, 2022; children positive for T trichiura on duplicate Kato-Katz smears and with infection intensity of 200 eggs per gram or more were eligible and treated first with albendazole (400 mg) and ivermectin (200 μg/kg) then with oxantel pamoate (20 mg/kg). We constructed a species tree of the Trichuris genus using 12 434 orthologous groups. We sequenced individual worms, which were used to confirm the phylogenetic placement and investigate patterns of adaptation through comparative genomic analyses. Finally, we conducted a GWAS to compare albendazole-ivermectin sensitive worms to drug non-sensitive worms. FINDINGS:670 children were screened, of whom 243 were enrolled and from whom 271 worms were isolated after the first treatment and 827 worms after the second treatment. Sufficient DNA was recovered from 747 worms of which 721 were suitable for further bioinformatic analysis; of these, 179 were albendazole-ivermectin sensitive worms and 542 were drug non-sensitive worms. We present and characterise a new, human-infecting Trichuris species named T incognita n sp, which is morphologically indistinguishable from T trichiura, but forms a distinct phylogenetic clade, closer to Trichuris suis than to the canonical human-infective T trichiura. Comparative genomic analysis of genes suspected to confer resistance to either albendazole or ivermectin in helminths revealed a high number of β-tubulin orthologs, present in the whole population of T incognita n sp, compared with the canonical T trichiura species, but these genes were not associated with a resistant phenotype. The GWAS did not provide conclusive evidence of adaptation to drug pressure within the same species. INTERPRETATION:Our results demonstrate that trichuriasis can be caused by multiple whipworm species, and that differences in response rates might result from species responding differently to drug treatment, rather than from the intraspecies establishment of resistance. This discovery, coupled with the high tolerability of T incognita n sp to albendazole-ivermectin, marks a substantial shift in how we understand and approach whipworm infections. FUNDING:European Research Council.
For over 30 years, detection and attribution (D A) studies have informed key conclusions in international and national assessments of climate science, providing compelling evidence for the reality and seriousness of anthropogenic effects on the global climate. In the early twenty-first century, D A methods were adapted to assess the contribution of climate change to longer-term trends in earth system processes and extreme weather events. More recently, attribution research quantified the health and economic impacts of climate change. Here we provide practical guidance to inform transdisciplinary collaboration among health, climate, and other relevant scientific disciplines and interested parties in designing, conducting, interpreting, and reporting robust and policy-relevant attribution analyses of human health outcomes. This guidance resulted from discussions among experts in health and climate science. Recommended steps include co-developing the research questions across disciplines; establishing a transdisciplinary analytic team with fundamental grounding in the core disciplines; engaging meaningfully with relevant interested parties and decision-makers to define an appropriate study design and analytic process, including defining the exposure event or trend; identifying, visualizing, and describing linkages in the causal pathway from exposure to weather/climate variables to the health outcome(s) of interest; choosing appropriate counterfactual climate data, and where applicable, to evaluate the skill of the climate and health impact model(s) used in D A research; quantifying the attributable changes in climate variables; quantifying the attributable health impacts within the context of other determinants of exposure and vulnerability; and reporting key results, including a description of how recommendations were incorporated into the analytical plan. Implementation of guidance would benefit diverse interested parties including researchers, research funders, policymakers, and climate litigation by harmonizing methods and increasing confidence in findings.
