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Global dataset of regions at the frontlines of cooling poverty risk
This global dataset of regions at the frontlines of cooling poverty risk includes five different files: (1) Global cooling demand in People-CDDs at ~1 km resolution (GeoTIFF), quantifying population-weighted cooling degree days by combining climate observations with gridded population data; (2) Global ability to access cooling in $/CDD per capita (PPP-adjusted) at ~10 km resolution (geoTIFF), estimating the economic capacity of populations to afford cooling by integrating GDP per capita with heat exposure; Population at the frontlines of cooling poverty risk at ~10 km resolution (geoTIFF), with two separate maps that identify populations (3) at high risk and (4) at extreme risk of cooling poverty by combining cooling demand, affordability constraints, and electricity costs; and (5) Summary of results by country in Excel, providing aggregated national-level indicators including total People-CDDs, economic capacity to afford cooling, and the population at high and extreme risk. Together, these datasets provide a global, spatially detailed estimate of cooling poverty risk under present-day climate conditions. Further information regarding the data sources and methods used to produce these datasets is available in the corresponding scientific article.
MAIT and other innate-like T cells integrate adaptive immune responses to modulate interval-dependent reactogenicity to mRNA vaccines.
Adenoviral (Ad) vectors and mRNA vaccines exhibit distinct patterns of immune responses and reactogenicity, but underpinning mechanisms remain unclear. We longitudinally compared homologous ChAdOx1 nCoV-19 and BNT162b2 vaccination, focusing on cytokine-responsive innate-like lymphocytes-mucosal-associated invariant T (MAIT) cells and Vδ2+ γδ T cells-which sense and tune innate-adaptive cross-talk. Ad priming elicited robust type I interferon (IFN)-mediated innate-like T cell activation, augmenting T cell responses (innate-to-adaptive signaling), which was dampened at boost by antivector immunity. Conversely, mRNA boosting enhanced innate-like responses, driven by prime-induced spike-specific memory T cell-derived IFN-γ (adaptive-to-innate signaling). Extending the dosing interval dampened inflammation at boost because of waning T cell memory. In a separate vaccine trial, preboost spike-specific T cells predicted severe mRNA reactogenicity regardless of the priming platform or interval. Overall, bidirectional innate-like and adaptive cross-talk, and IFN-γ-licensed innate-like T cells, orchestrate interval-dependent early vaccine responses, suggesting modifiable targets for safer, more effective regimens.
Malignancy Risk in Turner Syndrome+Y, Early Gonadectomy, and the Ethics of Parental Choices.
This case relates to an infant with Turner syndrome harboring the Y chromosome (TS+Y) and explores the boundaries of parental decision-making. Traditionally, gonads have been surgically removed in early childhood in this condition because of the risk of gonadoblastoma and potential malignant transformation. However, in the case discussed here, the infant's parents do not wish for surgery. In other differences of sex development resulting in intersex traits (increasingly termed congenital variations of sex characteristics [VSC]), some institutions report a shift in the last decade away from early surgical management, in favor of allowing children to be involved in decision-making when they are old enough to participate meaningfully. But should that approach change when there is a risk of malignancy? Two commentaries are presented. One outlines ethical considerations around early surgery in the case of VSC, highlighting implications for the child's bodily integrity and future sexual and reproductive autonomy. A second commentary analyzes the case in terms of pediatric ethics, medical uncertainty, and the zone of parental discretion. Both commentaries conclude that given a lack of adequate data to demonstrate net harms in delaying intervention, and some prospective benefit, it could be reasonable to defer surgery in accordance with the parental request.
Self-censorship: should scientific journals decline to publish self-experimentation?
A virologist recently made headlines after successfully using an experimental form of oncolytic virotherapy (OVT) to treat her own recurrent breast cancer. This case has come at a time when regulators are increasingly having to grapple with the proliferation of self-experimentation outside of accredited research institutions. There is therefore a pressing need to outline the key ethical dimensions of self-experimentation, and to develop ethical guidance for journals that may be faced with decisions about whether to publish research involving self-experimentation. In this paper, we aim to provide such guidance. We argue that whilst self-experimentation is not always ethically problematic, neither is there an in principle moral reason for exempting self-experimentation from ethical evaluation. After summarising the details of the recent case report of self-experimentation, and briefly placing it in historical context, we suggest that it is possible to navigate the ethical issues raised in cases of self-experimentation by returning to fundamental values in research ethics, focusing on the implications of self-experimentation for respect for respect for autonomy, reasonable risk, and preventing harm to others. We apply these principles to the case report, and explain why the publication of this report can be morally justified. We ultimately advocate for a case-by-case assessment of studies involving self-experimentation submitted for publication by ethical review boards and journal editors, and we propose a decision-making algorithm to help guide such decisions.
Targeting MHC-E as a new strategy for vaccines and immunotherapeutics
MHC-E is a highly conserved, non-polymorphic MHC protein that engages inhibitory and activating receptors on natural killer (NK) cells and T cells and can also present antigens to T cell receptors. NK cell responses driven by activating receptor interactions with MHC-E are implicated in controlling chronic viral infections and cancer. Immunotherapeutic targeting of interactions between MHC-E and inhibitory receptors to increase the activation of NK cells and T cells shows promise in improving antitumour immune responses. Furthermore, MHC-E-restricted CD8+ T cells elicited by cytomegalovirus-based vaccines might, for certain infections and cancers, be more effective than CD8+ T cells restricted by classical MHC class I or class II molecules. The ability of MHC-E to regulate or mediate both innate and adaptive immune responses independently of an individual’s MHC haplotype raises the possibility of new, universally effective vaccines and immunotherapies for infectious disease and cancer. Although the therapeutic exploitation of MHCE is still in its infancy, recent advances in the understanding of MHC-E biology show enormous potential, as described in this Review.
Value of using artificial intelligence derived clusters by health and social care need in primary care: A qualitative interview study with patients living with multiple long-term conditions, carers and health care professionals.
BACKGROUND: People living with MLTCs attending primary care often have unmet social care needs (SCNs), which can be challenging to identify and address. Artificial intelligence (AI) derived clusters could help to identify patients at risk of SCNs. Evidence is needed on views about the use of AI-derived clusters, to inform acceptable and meaningful implementation within interventions. METHOD: Qualitative semi-structured interviews (online and telephone), including a description of AI-derived clusters and a tailored vignette, with 24 people living with MLTCs and 20 people involved in the care of MLTCs (carers and health care professionals). Interviews were analysed using Reflexive and Codebook Thematic Analysis. RESULTS: Primary care was viewed as an appropriate place to have conversations about SCNs. However, participants felt health care professionals lack capacity to have these conversations and to identify support. AI was perceived as a tool that could potentially increase capacity but only when supplemented with effective, clinical conversations. Interventions harnessing AI should be brief, be easy to use and remain relevant over time, to ensure no additional burden on clinical capacity. Interventions must allow flexibility to be used by multidisciplinary teams within primary care, frame messages positively and facilitate conversations that remain patient centered. CONCLUSION: Our findings suggest that implementing AI-derived clusters to identify and support SCNs in primary care is perceived as valuable and can be used as a tool to inform and prioritse effective clinical conversations. But concerns must be addressed, including how AI-derived clusters can be used in a way that considers personal context.
Detection of Mycoplasma pneumoniae in hospitalized children with pneumonia in Laos
Mycoplasma pneumoniae has been described worldwide as an important cause of community-acquired pneumonia. From December 2013 to December 2014, 461 children admitted to Mahosot Hospital, Vientiane, Laos, with acute respiratory infection were investigated for upper respiratory microorganisms using probe-based real-time polymerase chain reaction (PCR) (FTD33). M. pneumoniae was detected by FTD33 in the upper respiratory tract of three patients, two girls and one boy, 5.7 and 3.9 years old and 13.6 years old, respectively. They presented with clinical features compatible with M. pneumoniae infection. They improved without M. pneumoniae directed therapy. The two girls were also positive for other potential pathogens. The boy had abnormal pulmonary auscultation, and one of the girls had significant anaemia. These results suggest that enhancement of diagnostic systems for M. pneumoniae detection is needed to improve understanding of the epidemiology of M. pneumoniae infection in Laos.
Direct real-time RT-PCR for the detection of dengue virus from patient serum in Lao PDR.
INTRODUCTION: Dengue fever is a growing global concern with an estimated 100-400 million infections every year and rising mortality over the past decade. In 2017, 40,000 deaths were attributed to dengue. Real-time reverse transcription PCR (RT-qPCR) is the gold standard technique to detect dengue virus (DENV) during the acute phase of the infection. However, it requires prior RNA purification which is costly and time consuming. We evaluated direct RT-qPCR using Luna Universal Probe One-Step RT-qPCR kit (Luna RT-qPCR) for the detection of DENV in sera. METHODS: Luna RT-qPCR conditions were optimized using DENV2 isolates. The efficiency of direct Luna RT-qPCR was evaluated on a panel of 132 patient sera using RNA purification (EZ1&2 Virus Mini Kit) followed by RT-qPCR (SuperScript III Platinum One-Step qRT-PCR system) as reference standard. RESULTS: The sensitivity (95% CI) of direct Luna RT-qPCR using neat patient sera was 34% (25-45). By reducing PCR inhibitors through a 1/10 dilution of the sera, the sensitivity improved to 86% (95% CI: 77-92). Comparable results were obtained between direct Luna RT-qPCR and reference standard process for samples with Cq