tbuckley/cabot-search huggingface dataset:
Beyond tuberculosis: a person-centred and rights-based approach to screening for household contacts
Authors: Claire J Calderwood, Collins Timire, Constancia Mavodza, Fungai Kavenga, Mxolisi Ngwenya, Karlos Madziva, Katherine Fielding, Justin Dixon, Rashida A Ferrand, Katharina Kranzer
Journal: The Lancet Global Health (2024)

Households affected by tuberculosis have syndemic vulnerability, reflecting a concentration of and interactions between multiple biomedical, psychosocial, and structural determinants of health. Traditional approaches to tuberculosis screening do not address pre-existing risks, such as undernutrition and other chronic conditions, or the indirect effects of tuberculosis, such as loss of livelihood. These pre-existing risks and consequences not only perpetuate the global tuberculosis epidemic but, for those affected, lead to poor health and deepen poverty. We propose reimagining tuberculosis screening as an opportunity to deliver a contextually relevant package of services that address the needs of households affected by tuberculosis. This approach puts people and their rights at the centre of efforts to end tuberculosis, and has equity at the core. This approach could support progress towards universal health coverage, benefiting communities and health systems. Leadership, flexibility in funding allocation, and innovative care models will be required to realise this approach at scale.
Transposable Element Insertions Are Associated with Batesian Mimicry in the Pantropical Butterfly <i>Hypolimnas misippus</i>
Authors: Anna Orteu, Marek Kucka, Ian J Gordon, Ivy Ng’iru, Eva S M van der Heijden, Gerard Talavera, Ian A Warren, Steve Collins, Richard H ffrench-Constant, Dino J Martins, Yingguang Frank Chan, Chris D Jiggins, Simon H Martin
Journal: Molecular Biology and Evolution (2024)

Hypolimnas misippus is a Batesian mimic of the toxic African Queen butterfly (Danaus chrysippus). Female H. misippus butterflies use two major wing patterning loci (M and A) to imitate three color morphs of D. chrysippus found in different regions of Africa. In this study, we examine the evolution of the M locus and identify it as an example of adaptive atavism. This phenomenon involves a morphological reversion to an ancestral character that results in an adaptive phenotype. We show that H. misippus has re-evolved an ancestral wing pattern present in other Hypolimnas species, repurposing it for Batesian mimicry of a D. chrysippus morph. Using haplotagging, a linked-read sequencing technology, and our new analytical tool, Wrath, we discover two large transposable element insertions located at the M locus and establish that these insertions are present in the dominant allele responsible for producing mimetic phenotype. By conducting a comparative analysis involving additional Hypolimnas species, we demonstrate that the dominant allele is derived. This suggests that, in the derived allele, the transposable elements disrupt a cis-regulatory element, leading to the reversion to an ancestral phenotype that is then utilized for Batesian mimicry of a distinct model, a different morph of D. chrysippus. Our findings present a compelling instance of convergent evolution and adaptive atavism, in which the same pattern element has independently evolved multiple times in Hypolimnas butterflies, repeatedly playing a role in Batesian mimicry of diverse model species.
Operational feasibility of Plasmodium vivax radical cure with tafenoquine or primaquine following point-of-care, quantitative glucose-6-phosphate dehydrogenase testing in the Brazilian Amazon: a real-life retrospective analysis
Authors: Marcelo Brito, Rosilene Rufatto, Felipe Murta, Vanderson Sampaio, Patrícia Balieiro, Djane Baía-Silva, Vanessa Castro, Brenda Alves, Aline Alencar, Stephan Duparc, Penny Grewal Daumerie, Isabelle Borghini-Fuhrer, Elodie Jambert, Cássio Peterka, Francisco Edilson Lima, Leonardo Carvalho Maia, Catherine Lucena Cruz, Bruna Maciele, Mariana Vasconcelos, Myrna Machado, Elder Augusto Figueira, Antônio Alcirley Balieiro, Alexandre Menezes, Roberta Ataídes, Dhelio Batista Pereira, Marcus Lacerda
Journal: The Lancet Global Health (2024)

To achieve malaria elimination, Brazil must implement Plasmodium vivax radical cure. We aimed to investigate the operational feasibility of point-of-care, quantitative, glucose-6-phosphate dehydrogenase (G6PD) testing followed by chloroquine plus tafenoquine or primaquine.
Deterministic Single‐Cell Encapsulation in PEG Norbornene Microgels for Promoting Anti‐Inflammatory Response and Therapeutic Delivery of Mesenchymal Stromal Cells
Authors: Hangjun Si, Yuanzhuo Chen, Kun Jiang, Ke Ma, Edward Ramsey, John Oakey, Mingming Sun, Zhongliang Jiang
Journal: Advanced Healthcare Materials (2024)

Abstract Tissue engineering at single‐cell resolution has enhanced therapeutic efficacy. Droplet microfluidics offers a powerful platform that allows deterministic single‐cell encapsulation into aqueous droplets, yet the direct encapsulation of cells into microgels remains challenging. Here, the design of a microfluidic device that is capable of single‐cell encapsulation within polyethylene glycol norbornene (PEGNB) hydrogels on‐chip is reported. Cells are first ordered in media within a straight microchannel via inertial focusing, followed by the introduction of PEGNB solution from two separate, converging channels. Droplets are thoroughly mixed by passage through a serpentine channel, and microgels are formed by photo‐photopolymerization. This platform uniquely enables both single‐cell encapsulation and excellent cell viability post‐photo‐polymerization. More than 90% of singly encapsulated mesenchymal stromal cells (MSCs) remain alive for 7 days. Notably, singly encapsulated MSCs have elevated expression levels in genes that code anti‐inflammatory cytokines, for example, IL‐10 and TGF‐β, thus enhancing the secretion of proteins of interest. Following injection into a mouse model with induced inflammation, singly encapsulated MSCs show a strong retention rate in vivo, reduce overall inflammation, and mitigate liver damage. These translational results indicate that deterministic single‐cell encapsulation could find use in a broad spectrum of tissue engineering applications.
Design and selection of drug properties to increase the public health impact of next-generation seasonal malaria chemoprevention: a modelling study
Authors: Lydia Braunack-Mayer, Josephine Malinga, Thiery Masserey, Narimane Nekkab, Swapnoleena Sen, David Schellenberg, André-Marie Tchouatieu, Sherrie L Kelly, Melissa A Penny
Journal: The Lancet Global Health (2024)

Seasonal malaria chemoprevention (SMC) is recommended for disease control in settings with moderate to high Plasmodium falciparum transmission and currently depends on the administration of sulfadoxine-pyrimethamine plus amodiaquine. However, poor regimen adherence and the increased frequency of parasite mutations conferring sulfadoxine-pyrimethamine resistance might threaten the effectiveness of SMC. Guidance is needed to de-risk the development of drug compounds for malaria prevention. We aimed to provide guidance for the early prioritisation of new and alternative SMC drugs and their target product profiles. In this modelling study, we combined an individual-based malaria transmission model that has explicit parasite growth with drug pharmacokinetic and pharmacodynamic models. We modelled SMC drug attributes for several possible modes of action, linked to their potential public health impact. Global sensitivity analyses identified trade-offs between drug elimination half-life, maximum parasite killing effect, and SMC coverage, and optimisation identified minimum requirements to maximise malaria burden reductions. Model predictions show that preventing infection for the entire period between SMC cycles is more important than drug curative efficacy for clinical disease effectiveness outcomes, but similarly important for impact on prevalence. When children younger than 5 years receive four SMC cycles with high levels of coverage (ie, 69% of children receiving all cycles), drug candidates require a duration of protection half-life higher than 23 days (elimination half-life >10 days) to achieve reductions higher than 75% in clinical incidence and severe disease (measured over the intervention period in the target population, compared with no intervention across a range of modelled scenarios). High coverage is crucial to achieve these targets, requiring more than 60% of children to receive all SMC cycles and more than 90% of children to receive at least one cycle regardless of the protection duration of the drug. Although efficacy is crucial for malaria prevalence reductions, chemoprevention development should select drug candidates for their duration of protection to maximise burden reductions, with the duration half-life determining cycle timing. Explicitly designing or selecting drug properties to increase community uptake is paramount. Bill & Melinda Gates Foundation and the Swiss National Science Foundation.
Estimating the subnational prevalence of antimicrobial resistant Salmonella enterica serovars Typhi and Paratyphi A infections in 75 endemic countries, 1990–2019: a modelling study
Authors: Annie J Browne, Michael G Chipeta, Frederick J Fell, Georgina Haines-Woodhouse, Bahar H Kashef Hamadani, Emmanuelle A P Kumaran, Gisela Robles Aguilar, Barney McManigal, Jason R Andrews, Elizabeth A Ashley, Allan Audi, Stephen Baker, Happy C Banda, Buddha Basnyat, Godfrey Bigogo, Chanpheaktra Ngoun, Vilada Chansamouth, Angeziwa Chunga, John D Clemens, Viengmon Davong, Gordon Dougan, Susanna J Dunachie, Nicholas A Feasey, Denise O Garrett, Melita A Gordon, Rumina Hasan, Andrea H Haselbeck, Nathaniel J Henry, Robert S Heyderman, Marianne Holm, Hyon Jin Jeon, Abhilasha Karkey, Farhana Khanam, Stephen P Luby, Faisal Riaz Malik, Florian Marks, Mayfong Mayxay, James E Meiring, Catrin E Moore, Patrick K Munywoki, Patrick Musicha, Paul N Newton, Gideok Pak, Koukeo Phommasone, Sunil Pokharel, Andrew J Pollard, Firdausi Qadri, Farah N Qamar, Sayaphet Rattanavong, Bobby Reiner, Tamalee Roberts, Samir Saha, Senjuti Saha, Sadia Shakoor, Mila Shakya, Andrew J Simpson, Jeff Stanaway, Claudia Turner, Paul Turner, Jennifer R Verani, Manivanh Vongsouvath, Nicholas P J Day, Mohsen Naghavi, Simon I Hay, Benn Sartorius, Christiane Dolecek
Journal: The Lancet Global Health (2024)

Enteric fever, a systemic infection caused by Salmonella enterica serovars Typhi and Paratyphi A, remains a major cause of morbidity and mortality in low-income and middle-income countries. Enteric fever is preventable through the provision of clean water and adequate sanitation and can be successfully treated with antibiotics. However, high levels of antimicrobial resistance (AMR) compromise the effectiveness of treatment. We provide estimates of the prevalence of AMR S Typhi and S Paratyphi A in 75 endemic countries, including 30 locations without data.
Innovative blood transfusion strategies to address global blood deserts: a consensus statement from the Blood Delivery via Emerging Strategies for Emergency Remote Transfusion (Blood DESERT) Coalition
Authors: Nakul P Raykar, Vanitha Raguveer, Yetmgeta Eyayou Abdella, Asma Ali-Awadh, Harshit Arora, Lucy Asamoah-Akuoko, Linda S Barnes, Andrew P Cap, Aulina Chowdhury, Zara Cooper, Meghan Delaney, Marisa DelSignore, Sidra Inam, Vijay Anand Ismavel, Kennedy Jensen, Nikathan Kumar, Gilchrist Lokoel, Joy John Mammen, Priyansh Nathani, Marie Paul Nisingizwe, Juan Carlos Puyana, Robert Riviello, Nobhojit Roy, Ali Salim, Claude Tayou-Tagny, Sargun Virk, Caroline Wesonga Wangamati
Journal: The Lancet Global Health (2024)

In rural settings worldwide, many people live in effective blood deserts without access to any blood transfusion. The traditional system of blood banking is logistically complex and expensive for many resource-restricted settings and demands innovative and multidisciplinary solutions. 17 international experts in medicine, industry, and policy participated in an exploratory process with a 2-day hybrid seminar centred on three promising innovative strategies for blood transfusions in blood deserts: civilian walking blood banks, intraoperative autotransfusion, and drone-based blood delivery. Participant working groups conducted literature reviews and interviews to develop three white papers focused on the current state and knowledge gaps of each innovation. Seminar discussion focused on defining blood deserts and developing innovation-specific implementation agendas with key research and policy priorities for future work. Moving forward, advocates should prioritise the identification of blood deserts and address the context-specific challenges for these innovations to alleviate the ongoing crisis in blood deserts.
Expectation maximisation pseudo labels
Authors: Moucheng Xu, Yukun Zhou, Chen Jin, Marius de Groot, Daniel C. Alexander, Neil P. Oxtoby, Yipeng Hu, Joseph Jacob
Journal: Medical Image Analysis (2024)

In this paper, we study pseudo-labelling. Pseudo-labelling employs raw inferences on unlabelled data as pseudo-labels for self-training. We elucidate the empirical successes of pseudo-labelling by establishing a link between this technique and the Expectation Maximisation algorithm. Through this, we realise that the original pseudo-labelling serves as an empirical estimation of its more comprehensive underlying formulation. Following this insight, we present a full generalisation of pseudo-labels under Bayes' theorem, termed Bayesian Pseudo Labels. Subsequently, we introduce a variational approach to generate these Bayesian Pseudo Labels, involving the learning of a threshold to automatically select high-quality pseudo labels. In the remainder of the paper, we showcase the applications of pseudo-labelling and its generalised form, Bayesian Pseudo-Labelling, in the semi-supervised segmentation of medical images. Specifically, we focus on: (1) 3D binary segmentation of lung vessels from CT volumes; (2) 2D multi-class segmentation of brain tumours from MRI volumes; (3) 3D binary segmentation of whole brain tumours from MRI volumes; and (4) 3D binary segmentation of prostate from MRI volumes. We further demonstrate that pseudo-labels can enhance the robustness of the learned representations. The code is released in the following GitHub repository: https://github.com/moucheng2017/EMSSL.
Accuracy and Feasibility of Real-time Continuous Glucose Monitoring in Critically Ill Patients After Abdominal Surgery and Solid Organ Transplantation
Authors: Barbora Voglová Hagerf, Marek Protus, Lenka Nemetova, Milos Mraz, Eva Kieslichova, Eva Uchytilova, Veronika Indrova, Jan Lelito, Peter Girman, Martin Haluzík, Janka Franekova, Veronika Svirlochova, David C. Klonoff, Michael A. Kohn, Antonin Jabor
Journal: Diabetes Care (2024)

Glycemia management in critical care is posing a challenge in frequent measuring and adequate insulin dose adjustment. In recent years, continuous glucose measurement has gained accuracy and reliability in outpatient and inpatient settings. The aim of this study was to assess the feasibility and accuracy of real-time continuous glucose monitoring (CGM) in ICU patients after major abdominal surgery.
Radiation-based immunogenic vaccine combined with a macrophage “checkpoint inhibitor” for boosting innate and adaptive immunity against metastatic colon cancers
Authors: Hongbo Xu, Xianya Qin, Yuanyuan Guo, Siyu Zhao, Xingxing Feng, Runzan Zhang, Tianyi Tian, Li Kong, Conglian Yang, Zhiping Zhang
Journal: Acta Pharmaceutica Sinica B (2024)

Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors. Especially, X-ray- induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants. However, we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines, which can specifically bind with the MerTK receptor on macrophages, acting as a "checkpoint" to facilitate immune silence in the tumor microenvironment. Therefore, we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250, a macrophage MerTK "checkpoint inhibitor," for treating peritoneal carcinomatosis in colon cancer. By incorporating UNC2250 into the treatment regimen, immunosuppressive efferocytosis of macrophages, which relies on MerTK-directed recognition of phosphatidylserine on vaccines, was effectively blocked. Consequently, the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages, thereby simultaneously eliciting robust adaptive and innate immunity. This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer.
Socioeconomic deprivation and racialised disparities in competitive athletes with sudden cardiac arrest from the USA
Authors: Megan Nicole Arthur, Randi N DeLong, Kristen Kucera, Barbara P Goettsch, Jared Schattenkerk, Sheree Bekker, Jonathan A Drezner
Journal: British Journal of Sports Medicine (2024)

Objective To explore the association of socioeconomic deprivation and racialised outcomes in competitive athletes with sudden cardiac arrest (SCA) in the USA. Methods SCA cases from the National Center for Catastrophic Sports Injury Research (July 2014 to June 2021) were included. We matched Area Deprivation Index (ADI) scores (17 metrics to grade socioeconomic conditions) to the 9-digit zip codes for each athlete’s home address. ADI is scored 1–100 with higher scores indicating greater neighbourhood socioeconomic deprivation. Analysis of variance was used to assess differences in mean ADI by racial groups. Tukey post hoc testing was used for pairwise comparisons. Results 391 cases of SCA in competitive athletes (85.4% male; 16.9% collegiate, 68% high school, 10.7% middle school, 4.3% youth) were identified via active surveillance. 79 cases were excluded due to missing data (19 race, 60 ADI). Of 312 cases with complete data, 171 (54.8%) were white, 110 (35.3%) black and 31 (9.9%) other race. The mean ADI was 40.20 (95% CI 36.64, 43.86) in white athletes, 57.88 (95% CI 52.65, 63.11) in black athletes and 40.77 (95% CI 30.69, 50.86) in other race athletes. Mean ADI was higher in black versus white athletes (mean difference 17.68, 95% CI 10.25, 25.12; p=0.0036) and black versus other race athletes (mean difference 17.11, 95% CI 4.74, 29.47; p&lt;0.0001). Conclusions Black athletes with SCA come from areas with higher neighbourhood socioeconomic deprivation than white or other race athletes with SCA. Our findings suggest that socioeconomic deprivation may be associated with racialised disparities in athletes with SCA.
Hyperuricemia Subtypes Classified According to Renal Uric Acid Handling Manifesting Distinct Phenotypic and Genetic Profiles in People With Gout
Authors: Han Qi, Mingshu Sun, Robert Terkeltaub, Tony R. Merriman, Haibing Chen, Zhiqiang Li, Aichang Ji, Xiaomei Xue, Wenyan Sun, Can Wang, Xinde Li, Yuwei He, Lingling Cui, Nicola Dalbeth, Changgui Li
Journal: Arthritis & Rheumatology (2024)

Hyperuricemia can be stratified into four subtypes according to renal uric acid handling. The aim of this study was to comprehensively describe the biologic characteristics (including genetic background) of clinically defined hyperuricemia subtypes in two large geographically independent gout cohorts.
Expansion of <scp>HLA‐DR</scp> Positive Peripheral Helper T and Naive B Cells in Anticitrullinated Protein <scp>Antibody‐Positive Individuals</scp> At Risk for Rheumatoid Arthritis
Authors: Hideto Takada, M. Kristen Demoruelle, Kevin D. Deane, Shohei Nakamura, Yasuhiro Katsumata, Katsunori Ikari, Jane H. Buckner, William H. Robinson, Jennifer A. Seifert, Marie L. Feser, LauraKay Moss, Jill M. Norris, Masayoshi Harigai, Elena W. Y. Hsieh, V. Michael Holers, Yuko Okamoto
Journal: Arthritis & Rheumatology (2024)

Objective To investigate immune dysregulation in the peripheral blood that contributes to the pre‐rheumatoid arthritis (RA) stage of RA development in anticitrullinated protein antibody (ACPA)+ individuals. Methods Using 37 markers by mass cytometry, we investigated peripheral blood mononuclear cells (PBMCs) from ACPA+ at‐risk individuals, ACPA+ early untreated patients with RA, and ACPA− controls in the Tokyo Women's Medical University cohort (n = 17 in each group). Computational algorithms, FlowSOM and Optimized t‐Distributed Stochastic Neighbor Embedding, were employed to explore specific immunologic differences between study groups. These findings were further evaluated, and longitudinal changes were explored, using flow cytometry and PBMCs from the US‐based Targeting Immune Responses for Prevention of RA cohort that included 11 ACPA+ individuals who later developed RA (pre‐RA), of which 9 had post‐RA diagnosis PBMCs (post‐RA), and 11 ACPA− controls. Results HLA‐DR + peripheral helper T (Tph) cells, activated regulatory T cells, PD‐1 hi CD8 + T cells, and CXCR5 − CD11c − CD38 + naive B cells were significantly expanded in PBMCs from at‐risk individuals and patients with early RA from the Tokyo Women's Medical University cohort. Expansion of HLA‐DR + Tph cells and CXCR5 − CD11c − CD38 + naive B cells was likewise found in both pre‐RA and post‐RA time points in the Targeting Immune Responses for Prevention of RA cohort. Conclusion The expansion of HLA‐DR + Tph cells and CXCR5 − CD11c − CD38 + naive B cells in ACPA+ individuals, including those who developed inflammatory arthritis and classified RA, supports a key role of these cells in transition from pre‐RA to classified RA. These findings may identify a new mechanistic target for treatment and prevention in RA. image
Active Anchoring Stimuli‐Responsive Nano‐Craft to Relieve Pulmonary Vasoconstriction by Targeting Smooth Muscle Cell for Hypoxic Pulmonary Hypertension Treatment
Authors: Mingxing Li, Xuwei Shang, Haiya Lou, Zixu Wang, Shanshan Xiang, Yihe Qiu, Fuqiang Hu, Fangying Yu, Hong Yuan
Journal: Advanced Healthcare Materials (2024)

Recently, nanotechnology-based drug delivery platforms in treating pulmonary arterial hypertension (PAH) have gradually emerged. However, large mechanical stress and shear stress in blood vessels greatly affect the retention of nanopreparative materials at lesion sites, severely limiting nanotechnology-based drug delivery. Herein, a stimuli-responsive nanocraft is rationally designed by actively anchoring E-selectin overexpressed on pulmonary arterial endothelial cells (PAECs), under hypoxic conditions, allowing effective accumulation and retention of the drug at the lesion site. Briefly, a nitrobenzene group is incorporated into the framework of a nanocarrier, and then it is simultaneously linked with chitosan. Additionally, the surface of the nanocarrier with sialic acid (SA) and encapsulated the clinically used drug ambrisentan (Am), which enables the anchoring of E-selectin and subsequent drug delivery is modifed. This system facilitates intercellular transport to pulmonary artery smooth muscle cells (PASMCs) when targeting PAECs and specifically responds to a reductive hypoxic microenvironment with elevated nitroreductase in PASMCs. Moreover, compared with free Am, nanoencapsulation and SA-PEG