tbuckley/cabot-search huggingface dataset:
Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunction-associated steatotic liver disease
Authors: Eiji Kakazu, Masaaki Mino, Tatsuya Kanto
Journal: Clinical and Molecular Hepatology (2025)

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its relatively advanced form, metabolic dysfunction-associated steatohepatitis (MASH), are becoming increasingly prevalent worldwide, making their prevention and management an urgent global health priority. Central to their development are key metabolic defects, including abnormal concentrations of monosaccharides, fatty acids, and amino acids, but the complex relationships between these substances within the hepatic microenvironment remain only partially understood. Dysregulated glucose metabolism and selective insulin resistance (IR) promote hepatic gluconeogenesis, glycolysis, and de novo lipogenesis (DNL); and excessive concentrations of free fatty acids from the diet and adipose tissue drive steatosis. Emerging evidence also implies that amino acid metabolism affects mitochondrial function and redox balance. Dysfunctional mitochondrial oxidative phosphorylation and the associated increase in reactive oxygen species production further exacerbate the cellular stress, inflammation, and fibrosis. However, compared with monosaccharide and fatty acid metabolism, the role of amino acid metabolism in MASLD/MASH remains less well understood. A better understanding of the role of such metabolic dysfunction in liver pathobiology should aid the identification of more useful biomarkers and precision therapies for MASLD/MASH.
Firearm availability and firearm incidents: quasi-experimental analysis using start of US hunting seasons
Authors: Christopher M Worsham, Charles F Bray, Anupam B Jena
Journal: BMJ (2025)

Abstract Objective To take advantage of the arbitrarily timed increase in firearm and ammunition availability brought on by the start of deer hunting seasons to study its impact on hunting, and importantly, non-hunting related firearm incidents. Design Quasi-experimental analysis using start of hunting season in United States. Setting Populations of US states with highest number of hunting accidents reported in the Gun Violence Archive for deer hunting seasons between 2016 and 2019. Participants 10 US states (Alabama, Indiana, Michigan, Minnesota, Missouri, New York, Ohio, Pennsylvania, Texas, and Wisconsin). Main outcomes and measures Average per capita weekly rates of firearm incidents overall and among specified categories of firearm incidents in the periods before, during, and after the opening of deer hunting seasons combined into a single analysis across four years and 10 states, adjusting for state fixed effects. Results Compared with control periods before and after the opening period, the start of the hunting season was associated with a 12.3% relative increase in the rate of firearm incidents overall (absolute change 1.34-1.50 incidents per 10 million population; 95% confidence interval for relative change 3.0% to 21.6%, P&lt;0.01). Relative increases were observed for incidents categorized as hunting incidents (absolute change &lt;0.01-0.05 per 10 million; relative change 566%), suicide (0.70-0.77; 11.1%), incidents involving alcohol or other substances (0.07-0.13; 87.5%), domestic violence (0.13-0.16; 27.4%), defensive use (0.08-0.10; 27.8%), home invasion or robbery (0.13-0.17; 30.4%), and incidents related to firearm carry licenses (0.40-0.48; 19.4%). No differences were observed for incidents involving children or police officers. Conclusions The start of hunting season was associated with increased rates of hunting and non-hunting related firearm incidents, most plausibly because of the increased availability of firearms and ammunition. The results suggest that efforts to promote firearm safety at the beginning of hunting season could help reduce hunting and non-hunting related firearm incidents.
Tough and waterproof microneedles overcome mucosal immunotolerance by modulating antigen release patterns
Authors: Penghui He, Chunting He, Rong Guo, Yangsen Ou, Yu Chang, Zhiqiang Xie, Xue Tang, Yanhua Xu, Yuanhao Zhao, Hairui Wang, Zhaofei Guo, Shuting Bai, Zhengjun Chen, Fan Fan, Guangsheng Du, Xun Sun
Journal: Journal of Controlled Release (2025)
Fibroblast derived C3 promotes the progression of experimental periodontitis through macrophage M1 polarization and osteoclast differentiation
Authors: Feilong Ren, Shize Zheng, Huanyu Luo, Xiaoyi Yu, Xianjing Li, Shaoyi Song, Wenhuan Bu, Hongchen Sun
Journal: International Journal of Oral Science (2025)

Abstract Complement C3 plays a critical role in periodontitis. However, its source, role and underlying mechanisms remain unclear. In our study, by analyzing single-cell sequencing data from mouse model of periodontitis, we identified that C3 is primarily derived from periodontal fibroblasts. Subsequently, we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis. C3ar −/− mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice, characterized by mild gingival tissue damage and reduced alveolar bone loss. This reduction was associated with decreased production of pro-inflammatory mediators and reduced osteoclast infiltration in the periodontal tissues. Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation. Finally, by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis, we found that the results observed in mice were consistent with human data. Therefore, our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis, driven by macrophage M1 polarization and osteoclast differentiation. These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy
Authors: Rubika Balendra, Jemeen Sreedharan, Martina Hallegger, Raphaëlle Luisier, Hilal A Lashuel, Jenna M Gregory, Rickie Patani
Journal: The Lancet Neurology (2025)
From health assemblies to climate negotiations: youth perspectives on existing gaps in global climate action
Authors: Farah Waseem, Anouk Suzanne Nusselder, Salman Khan, Carlotta Oltmanns, Beth Elinor Stinchcombe, Arwa Hany Sharaby, Thashreef Karimb Valappil, Iris Martine Blom
Journal: The Lancet Planetary Health (2025)
Impact of climate change on arsenic concentrations in paddy rice and the associated dietary health risks in Asia: an experimental and modelling study
Authors: Dongming Wang, Brent F Kim, Keeve E Nachman, Andrea A Chiger, Julie Herbstman, Irakli Loladze, Fang-Jie Zhao, Chuan Chen, Axiang Gao, Yongguan Zhu, Fangbai Li, Ren Fang Shen, Xiaoyuan Yan, Jiabao Zhang, Chuang Cai, Lian Song, Min Shen, Chuanqi Ma, Xiong Yang, Wei Zhou, Yujun Wang, Haoye Tang, Yu Jiang, Yanfeng Ding, Wuxing Liu, Jianqiang Sun, Wei Zhou, Ana Navas-Acien, Chunwu Zhu, Lewis H Ziska
Journal: The Lancet Planetary Health (2025)

Rising global atmospheric carbon dioxide (CO2) concentrations and surface temperatures could negatively affect rice yields and nutritional quality; however, their effects on arsenic accumulation in paddy rice have not been assessed concurrently. We aimed to assess the impact of increases in CO2 and temperature (individually and in combination) on arsenic concentrations in rice, characterise soil properties that might influence arsenic uptake, and model the associated risks of cancer and other health outcomes due to increased arsenic exposure. For this modelling study we performed in-situ multi-varietal trials using Free-Air CO2 Enrichment platforms with and without supplemental temperature to examine the bioaccumulation of arsenic in paddy rice and the underlying biogeochemical mechanisms from 2014 to 2023. We modelled dietary inorganic arsenic exposure and the associated risks of cancer and non-cancer health outcomes via rice consumption for seven of the leading rice-consuming countries in east and southeast Asia. Concomitant increases in CO2 and temperature resulted in a synergistic increase of inorganic arsenic in rice grain. The observed increase is likely to be related to changes in soil biogeochemistry that favoured reduced arsenic species. Modelled consumption of rice under these conditions resulted in projected increases in inorganic arsenic exposure and lifetime cancer and health risks for multiple Asian countries by 2050. Inorganic arsenic exposure and the associated health consequences might increase in rice grain grown in flooded systems with mid-century climate projections. The current assessment reinforces the urgent need for mitigation of arsenic exposure in rice relative to near-term climate change. National Key Research and Development Program of China, National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, China, Carbon Peaking and Carbon Neutrality Special Fund for Science and Technology from Nanjing Science and Technology Bureau, Key Research and Development Program of Jiangsu Province, Erdos City Science and Technology Major Project, Science Foundation of the Chinese Academy of Sciences, Carbon Peaking and Carbon Neutrality Special Fund for Science and Technology from Jiangsu Science and Technology Department, and "0-1" Original Innovation Project of the Chinese Academy of Sciences.
Disentangling the contributions of anthropogenic climate change, greenhouse gases, and aerosols to heat-related mortality in Great Britain: a climate change impact attribution study
Authors: Kai Wan, David Gampe, Shakoor Hajat
Journal: The Lancet Planetary Health (2025)

Anthropogenic aerosols are a critical contributor to climate change and their net cooling effects can partially counter the warming effects of greenhouse gases, but they are rarely considered in health impact attribution studies of climate change. The aim of this study was to attribute heat-related deaths in Great Britain to anthropogenic climate change and individual forcings of greenhouse gases and aerosols. Using a special suite of climate simulations, past and future heat-related deaths in Great Britain attributable to the relative contributions of anthropogenic greenhouse gas and aerosol forcings were estimated under the Shared Socioeconomic Pathway SSP2-4.5. Empirical confidence intervals were quantified combining uncertainties from climate models and health risk functions. Emergence of heat-related mortality associated with anthropogenic climate change was partially counteracted by the cooling effects of aerosols, with the time of emergence being approximately four decades later compared with the greenhouse gas-only simulation. We estimate that around 700 annual heat-related deaths during 1961-1980 were masked by the cooling effects of aerosols. There was a sharp increase in heat-deaths between 1980 and 2020 due to the combined effects of greenhouse gas increases and large aerosol reductions. By the end of the 21st century, a 2-6-fold increase in heat-related deaths due to greenhouse gases is projected, with a negligible counteracting contribution of aerosols. In addition to greenhouse gases, the potential contributions of aerosols should be considered when assessing climate change risks and mitigation pathways. This is crucial due to their opposing temperature effects, diverging future emission trajectories, and varying geographical scales. Separate attribution of climate change impacts to the global effects of greenhouse gases and local effects of aerosols can enhance transparency and equity, and can inform loss and damage funding models. Such impact attribution assessments can help to optimise health co-benefits and prevent unintended negative consequences of environmental policies on heat-related and air pollution-related health outcomes. Health Protection Research Unit in Environmental Change and Health, National Institute for Health and Care Research.
Urban Aedes aegypti suitability indicators: a study in Rio de Janeiro, Brazil
Authors: Steffen Knoblauch, Rutendo T Mukaratirwa, Paulo F P Pimenta, Antônio A de A Rocha, Myat Su Yin, Sukanya Randhawa, Sven Lautenbach, Annelies Wilder-Smith, Joacim Rocklöv, Oliver J Brady, Filip Biljecki, Peter Dambach, Thomas Jänisch, Bernd Resch, Peter Haddawy, Till Bärnighausen, Alexander Zipf
Journal: The Lancet Planetary Health (2025)

Controlling Aedes aegypti stands as the primary strategy in curtailing the global threat of vector-borne viral infections such as dengue fever, which is responsible for around 400 million infections and 40 000 fatalities annually. Effective interventions require a precise understanding of Ae aegypti spatiotemporal distribution and behaviour, particularly in urban settings where most infections occur. However, conventionally applied sample-based entomological surveillance systems often fail to capture the high spatial variability of Ae aegypti that can arise from heterogeneous urban landscapes and restricted Aedes flight range. In this study, we aimed to address the challenge of capturing the spatial variability of Ae aegypti by leveraging emerging geospatial big data, including openly available satellite and street view imagery, to locate common Ae aegypti breeding habitats. These data enabled us to infer the seasonal suitability for Ae aegypti eggs and larvae at a spatial resolution of 200 m within the municipality of Rio de Janeiro, Brazil. The proposed microhabitat and macrohabitat indicators for immature Ae aegypti explained the distribution of Ae aegypti ovitrap egg counts by up to 72% (95% CI 70-74) and larval counts by up to 74% (72-76). Spatiotemporal interpolations of ovitrap counts, using suitability indicators, provided high-resolution insights into the spatial variability of urban immature Ae aegypti that could not be captured with sample-based surveillance techniques alone. The potential of the proposed method lies in synergising entomological field measurements with digital indicators on urban landscape to guide vector control and address the prevailing spread of Ae aegypti-transmitted viruses. Estimating Ae aegypti distributions considering habitat size is particularly important for targeting novel vector control interventions such as Wolbachia. German Research Foundation and Austrian Science Fund.
Maternal mastitis and streptococcal toxic shock syndrome risk from breastfeeding children with scarlet fever: case report and literature review
Authors: Sonja Dahmann, Maximilian Kueckelhaus, Philipp Wiebringhaus, David Kampshoff, Carl Opitz, Joke Tio, Michael Ney, Andreas Itzek, Tobias Hirsch, Alexander Dermietzel
Journal: The Lancet Infectious Diseases (2025)

Lactational mastitis is a common condition during breastfeeding, which, in rare cases, can progress to life-threatening necrotising mastitis, particularly in cases where Streptococcus pyogenes is involved. The development of streptococcal toxic shock syndrome (STSS) is associated with a fatality rate of approximately 50%. In this Grand Round, we present the case of a healthy mother, aged 35 years, breastfeeding a child diagnosed with scarlet fever. The mother subsequently developed lactational mastitis, with a high load of S pyogenes, culminating in skin necrosis and STSS. This case, along with six more case reports identified in a thorough literature search, underscores the severity of lactational S pyogenes mastitis. In all cases, the only identifiable risk factor for invasive S pyogenes disease was close contact to individuals exhibiting symptoms of scarlet fever. During breastfeeding, the direct contact of the nipple to the child's pharynx, containing S pyogenes in the case of scarlet fever, presents a probable route of transmission, especially when considering the pathogenicity of the bacterium. Although breastfeeding is generally encouraged, the current literature lacks sufficient guidance regarding breastfeeding practices in children with scarlet fever. This Grand Round proposes a simple strategy to minimise maternal risks, offering valuable insights into clinical management and prevention.
A health impact assessment of progress towards urban nature targets in the 96 C40 cities
Authors: Greta K Martin, David Rojas-Rueda, Kelvin C Fong, Marcia Pescador Jimenez, Patrick L Kinney, Robert Canales, Susan C Anenberg
Journal: The Lancet Planetary Health (2025)

Urban greenspaces (eg, parks and trees) and blue spaces (eg, rivers and coasts) improve climate regulation and human health. In 2021, the mayors of 31 cities in the C40 Climate Leadership Group set 2030 targets for the percentage of urban greenspace and population with nearby natural (green or blue) space. We quantified annual all-cause mortality reductions from progress towards these targets for C40's 96 member cities. We conducted a quantitative health impact assessment, testing three illustrative scenarios to increase urban greenspace: uniformly across space, in areas with the least nature, and in the most populated areas. We converted one percentage point progress towards each target in terms of the Normalized Difference Vegetation Index (NDVI) using previously published associations. We used mortality rate estimates from The Global Burden of Diseases, Injuries, and Risk Factors Study, population data from WorldPop, and a pooled hazard ratio of NDVI and all-cause mortality from an epidemiological meta-analysis. Uniformly increasing greenspace by 1% yielded an estimated 96-city median of 1·77 (range 0·65-3·52, IQR 1·46-2·19) fewer annual premature deaths per 100 000 population; increasing the population percentage with nearby natural space yielded an estimated median of 0·56 (range 0·11-1·70, IQR 0·44-0·69) fewer annual premature deaths per 100 000 population. On average, compared with uniform increases, adding greenspace in the least natural areas provided 1·4-1·7 times (depending on the target) the health benefits, and adding greenspace in the most populated areas provided 2·7 times the health benefits. The geographical distribution of greenspace expansion influences the magnitude of associated health benefits across varied urban contexts. Health benefits are largest when greenspace is added near population centres. Wellcome Trust, NASA, and The George Washington University.
Blood under pressure: how climate change threatens blood safety and supply chains
Authors: Elvina Viennet, Melinda M Dean, Jorga Kircher, Karin Leder, Yuming Guo, Phoebe Jones, Helen M Faddy
Journal: The Lancet Planetary Health (2025)

Climate change substantially threatens public health, including the blood supply chain, which is crucial for medical treatments such as surgeries, trauma care, and chronic disease management. Extreme weather events, vector-borne disease shifts, and temperature fluctuations can disrupt blood collection, testing, transport, and storage, threatening both the safety and sufficiency of blood products. Although studies have highlighted some connections between climate change, transfusion-transmissible infections, and blood safety, there remains a lack of comprehensive understanding of the climate effects on each supply chain stage. In this Personal View, we address the potential climate-driven challenges across the blood supply chain, from donor health to blood component stability, emphasising the importance of proactive measures. To protect the availability and safety of blood supplies in an evolving climate, further research and adaptive strategies are needed to build a resilient blood supply system that can withstand emerging climate-related disruptions.
Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomised, head-to-head, phase 3 trial
Authors: Ana Maria Giménez-Arnau, Andreas Pinter, Wiebke Sondermann, Ziad Reguiai, Richard Woolf, Charles Lynde, Franz J Legat, Antonio Costanzo, Juan F Silvestre, Natja Mellerup, Marie Louise Østerdal, Ursula Plohberger, Lasse Ryttig, Andrea Bauer
Journal: The Lancet (2025)
Syntropic farming systems for reconciling productivity, ecosystem functions, and restoration
Authors: Johanna Jacobi, Christian Andres, Farhah F Assaad, Stéphane Bellon, Xavier Coquil, Sebastian Doetterl, Dayana Naimid Esnarriaga, Diana Ortiz-Vallejo, Cyrille Rigolot, Johanna Rüegg, Sylvain Takerkart, Martin Trouillard, Boris Vilter, Janina Dierks
Journal: The Lancet Planetary Health (2025)

Inspired by the succession and vertical stratification found in nature, syntropic farming systems (SFS) incorporate annual and perennial plants in diversified farming systems. Numerous practice examples show the potential of SFS to enhance agroecosystems via optimised design and active management. Yet, scientific knowledge on SFS remains scarce, especially in the temperate zone. We compiled findings on the outcomes and enablers of SFS from 67 studies comprising diverse SFS designs-mainly from tropical countries-that have the potential to be implemented in temperate agricultural landscapes. Most studies highlight the high agrobiodiversity, nutritional diversity, and yield quality of SFS. Comparing the productivity of SFS with other farming systems shows mixed results. Carbon storage, soil fertility, water cycling, climate resilience, and plant health appear favourable in SFS across widely varying cropping systems and environments. SFS can also provide meaningful and dignified work. Nevertheless, remaining obstacles include high labour demand, intensive knowledge requirements, availability of tools and machines for SFS, and a lack of enabling policies. Efforts should focus on harnessing SFS to address the escalating socioecological crises in agri-food systems worldwide, including those of intensively managed cropland systems in the temperate zone where SFS systems could help to redesign agricultural landscapes.
The impact of ecosystem nitrogen enrichment on pollen allergy: a cross-sectional paired comparison study
Authors: Robin Daelemans, Paulien Verscheure, Thomas Rombouts, Sien Keysers, Arne Devriese, Gerrit Peeters, Lieve Coorevits, Glynis Frans, Laura Van Gerven, Nicolas Bruffaerts, Olivier Honnay, Tobias Ceulemans, Raf Aerts, Rik Schrijvers
Journal: The Lancet Planetary Health (2025)

The prevalence of allergy to aeroallergens is rising, driven by both environmental and lifestyle changes. However, the role of ubiquitous nitrogen enrichment in exacerbating pollen allergy remains unclear. This study aimed to investigate the impact of nitrogen on pollen allergenicity by connecting the resulting ecological changes with allergic outcomes. We conducted a cross-sectional paired comparison study, examining differences between nitrogen-enriched (fertilised) and non-enriched common semi-natural grasslands in Belgium. Pollen from paired grasslands (n=50, enriched [n=25] vs non-enriched [n=25]) based on their common geography, were sampled following a standardised protocol. We analysed grassland pollen abundance, quantified pollen species composition via DNA sequencing, and assessed pollen allergenicity using basophil activation testing and specific IgE measurements in a cross-sectional sample of adults who were allergic to grass pollen (n=20). Basophil activation test outcome measures included area under the dose-response curve, maximal reactivity (CD63max), and effective concentration eliciting 50% basophil activation. Nitrogen-enriched grasslands produced significantly more pollen, with a 6·2-fold increase compared with their unfertilised counterparts (3·6 mg/m2vs 0·6 mg/m2). When normalised to protein content, pollen from these enriched grasslands showed increased allergenic potential, with 5·1 times higher basophil activation test sensitivity and a 1·3-fold increase in specific IgE titres compared with their unfertilised counterparts (geometric mean fertilised 3·63 kUA/L vs unfertilised 2·81 kUA/L). Nitrogen enrichment substantially increased pollen abundance and allergenicity, indicating a heightened allergy burden in nitrogen-rich environments. These findings underscore the need for policies addressing nitrogen pollution to mitigate its public health impacts. Belgian Science Policy Office.