tbuckley/cabot-search huggingface dataset:
Bioinspired engineering ADSC nanovesicles thermosensitive hydrogel enhance autophagy of dermal papilla cells for androgenetic alopecia treatment
Authors: Jiachao Xiong, Zhixiao Liu, Lingling Jia, Yulin Sun, Rong Guo, Tingting Xi, Zihan Li, Minjuan Wu, Hua Jiang, Yufei Li
Journal: Bioactive Materials (2024)

Androgenic alopecia (AGA) is a highly prevalent form of non-scarring alopecia but lacks effective treatments. Stem cell exosomes have similar repair effects to stem cells, suffer from the drawbacks of high cost and low yield yet. Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes, enabling them to efficiently encapsulate substantial quantities of therapeutic proteins. In this study, we observed that JAM-A, an adhesion protein, resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages, thereby facilitating the process of hair regrowth in cases of AGA. Consequently, adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles (JAM-AOE@NV). The incorporation of JAM-AOE@NV into a thermosensitive hydrogel matrix (JAM-AOE@NV Gel) to effectively addresses the limitations associated with the short half-life of JAM-AOE@NV, and resulted in the achievement of a sustained-release profile for JAM-AOE@NV. The physicochemical characteristics of the JAM-AOE@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro. The JAM-AOE@NV Gel, thus, presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA.
The electrophysiologic effects of <i>KCNQ1</i> extend beyond expression of <i>I</i>Ks: evidence from genetic and pharmacologic block
Authors: Yuko Wada, Lili Wang, Lynn D Hall, Tao Yang, Laura L Short, Joseph F Solus, Andrew M Glazer, Dan M Roden
Journal: Cardiovascular Research (2024)

While variants in KCNQ1 are the commonest cause of the congenital long QT syndrome, we and others find only a small IKs in cardiomyocytes from human-induced pluripotent stem cells (iPSC-CMs) or human ventricular myocytes.
Climate change-related distributional range shifts of venomous snakes: a predictive modelling study of effects on public health and biodiversity
Authors: Pablo Ariel Martinez, Irene Barbosa da Fonseca Teixeira, Tuany Siqueira-Silva, Franciely Fernanda Barbosa da Silva, Luiz Antônio Gonzaga Lima, Jonatas Chaves-Silveira, Miguel Ångel Olalla-Tárraga, José María Gutiérrez, Talita Ferreira Amado
Journal: The Lancet Planetary Health (2024)

BackgroundClimate change is expected to have profound effects on the distribution of venomous snake species, including reductions in biodiversity and changes in patterns of envenomation of humans and domestic animals. We estimated the effect of future climate change on the distribution of venomous snake species and potential knock-on effects on biodiversity and public health.MethodsWe built species distribution models based on the geographical distribution of 209 medically relevant venomous snake species (WHO categories 1 and 2) and present climatic variables, and used these models to project the potential distribution of species in 2070. We incorporated different future climatic scenarios into the model, which we used to estimate the loss and gain of areas potentially suitable for each species. We also assessed which countries were likely to gain new species in the future as a result of species crossing national borders. We integrated the species distribution models with different socioeconomic scenarios to estimate which countries would become more vulnerable to snakebites in 2070.FindingsOur results suggest that substantial losses of potentially suitable areas for the survival of most venomous snake species will occur by 2070. However, some species of high risk to public health could gain climatically suitable areas for habitation. Countries such as Niger, Namibia, China, Nepal, and Myanmar could potentially gain several venomous snake species from neighbouring countries. Furthermore, the combination of an increase in climatically suitable areas and socioeconomic factors (including low-income and high rural populations) means that southeast Asia and Africa (and countries including Uganda, Kenya, Bangladesh, India, and Thailand in particular) could have increased vulnerability to snakebites in the future, with potential effects on public human and veterinary health.InterpretationLoss of venomous snake biodiversity in low-income countries will affect ecosystem functioning and result in the loss of valuable genetic resources. Additionally, climate change will create new challenges to public health in several low-income countries, particularly in southeast Asia and Africa. The international community needs to increase its efforts to counter the effects of climate change in the coming decades.FundingGerman Research Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, German Centre for Integrative Biodiversity Research, Ministerio de Ciencia e Innovación de España, European Regional Development Fund.
Impact of price reductions, subsidies, or financial incentives on healthy food purchases and consumption: a systematic review and meta-analysis
Authors: Peijue Huangfu, Fiona Pearson, Farah Marwan Abu-Hijleh, Charlotte Wahlich, Kathryn Willis, Susanne F Awad, Laith J Abu-Raddad, Julia A Critchley
Journal: The Lancet Planetary Health (2024)

Poor diets are a global concern and are linked with various adverse health outcomes. Healthier foods such as fruit and vegetables are often more expensive than unhealthy options. This study aimed to assess the effect of price reductions for healthy food (including fruit and vegetables) on diet. We performed a systematic review and meta-analysis on studies that looked at the effects of financial incentives on healthy food. Main outcomes were change in purchase and consumption of foods following a targeted price reduction. We searched electronic databases (MEDLINE, EconLit, Embase, Cinahl, Cochrane Library, and Web of Science), citations, and used reference screening to identify relevant studies from Jan 1, 2013, to Dec 20, 2021, without language restrictions. We stratified results by population targeted (low-income populations vs general population), the food group that the reduction was applied to (fruit and vegetables, or other healthier foods), and study design. Percentage price reduction was standardised to assess the effect in meta-analyses. Study quality was assessed using the Cochrane Risk of Bias tool and Newcastle-Ottawa Scale. 34 studies were eligible; 15 took place in supermarkets and eight took place in workplace canteens in high-income countries, and 21 were targeted at socioeconomically disadvantaged communities. Pooled analyses of 14 studies showed a price reduction of 20% resulted in increases in fruit and vegetable purchases by 16·62% (95% CI 12·32 to 20·91). Few studies had maintained the price reduction for over 6 months. In conclusion, price reductions can lead to increases in purchases of fruit and vegetables, potentially sufficient to generate health benefits, if sustained.
Underestimating the crowd
Authors: None The Lancet Planetary Health
Journal: The Lancet Planetary Health (2024)

Climate mitigation policy is fundamentally simple; we need to cut carbon emissions steeply to prevent additional increments of warming that will make the world increasingly less hospitable for everyone. There is a very strong scientific, and clear international political consensus that this is what needs to happen. Yet we are being very slow in implementing these changes. Why is this?
Correlations of response rate and progression-free survival with overall survival in immunotherapy trials for metastatic non-small-cell lung cancer: an FDA pooled analysis
Authors: Bernardo Haddock Lobo Goulart, Sirisha L Mushti, Somak Chatterjee, Erin Larkins, Pallavi S Mishra-Kalyani, Richard Pazdur, Paul G Kluetz, Harpreet Singh
Journal: The Lancet Oncology (2024)
Ambient heat and acute kidney injury: case-crossover analysis of 1 354 675 automated e-alert episodes linked to high-resolution climate data
Authors: Shakoor Hajat, Anna Casula, Peninah Murage, Daniel Omoyeni, Tom Gray, Zoe Plummer, Retha Steenkamp, Dorothea Nitsch
Journal: The Lancet Planetary Health (2024)

BackgroundAs global temperatures continue to rise, the effects of ambient heat on acute kidney injury (AKI) are of growing concern. We used a novel nationwide electronic alert (e-alert) system to detect increases in AKI risk associated with high temperatures.MethodsWe used a case-crossover design to link 1 354 675 AKI episodes occurring in England between April and September in years 2017–2021 to daily maximum temperature data at postcode sector level. AKI episode data were obtained from the UK Renal Registry. There were no further inclusion or exclusion criteria. Conditional logistic regression employing distributed lag non-linear models was used to assess odds of AKI episode on case days compared with day-of-week matched control days. Effects during heatwaves were also assessed using heat-episode analysis.FindingsThere were strongly increased odds of AKI episode associated with high temperatures, with odds ratio (OR) 1·623 (95% CI 1·319–1·997) on a day of temperature 32°C compared with one of 17°C, the effects being strongest on a lag of 1 day. There was an OR of 1·020 (1·019–1·020) per 1°C increase in temperature above 17°C. The odds of a heat-related AKI episode were similar between AKI stages 1 and 2, but considerably lower for stage 3 events. A 7-day heatwave in July 2021 was associated with a 28·6% increase in AKI counts (95% CI 26·5–30·7).InterpretationHeat-related AKI is a growing public health challenge. As even small changes in renal function can affect patient outcomes, susceptible individuals should be advised to take preventive measures whenever hot weather is forecast. Use of an e-alert system allows effects in milder cases that do not require secondary care to also be detected.FundingNational Institute for Health and Care Research (NIHR).
Estimates of global mortality burden associated with short-term exposure to fine particulate matter (PM2·5)
Authors: Wenhua Yu, Rongbin Xu, Tingting Ye, Michael J Abramson, Lidia Morawska, Bin Jalaludin, Fay H Johnston, Sarah B Henderson, Luke D Knibbs, Geoffrey G Morgan, Eric Lavigne, Jane Heyworth, Simon Hales, Guy B Marks, Alistair Woodward, Michelle L Bell, Jonathan M Samet, Jiangning Song, Shanshan Li, Yuming Guo
Journal: The Lancet Planetary Health (2024)

BackgroundThe acute health effects of short-term (hours to days) exposure to fine particulate matter (PM2·5) have been well documented; however, the global mortality burden attributable to this exposure has not been estimated. We aimed to estimate the global, regional, and urban mortality burden associated with short-term exposure to PM2·5 and the spatiotemporal variations in this burden from 2000 to 2019.MethodsWe combined estimated global daily PM2·5 concentrations, annual population counts, country-level mortality rates, and epidemiologically derived exposure–response functions to estimate the mortality attributable to short-term PM2·5 exposure from 2000 to 2019, in the continental regions and in 13 189 urban centres worldwide at a spatial resolution of 0·1° × 0·1°. We tested the robustness of our mortality estimates with different theoretical minimum risk exposure levels, lag effects, and exposure–response functions.FindingsApproximately 1 million (95% CI 690 000–1·3 million) premature deaths per year from 2000 to 2019 were attributable to short-term PM2·5 exposure, representing 2·08% (1·41–2·75) of total global deaths or 17 (11–22) premature deaths per 100 000 population. Annually, 0·23 million (0·15 million–0·30 million) deaths attributable to short-term PM2·5 exposure were in urban areas, constituting 22·74% of the total global deaths attributable to this cause and accounting for 2·30% (1·56–3·05) of total global deaths in urban areas. The sensitivity analyses showed that our worldwide estimates of mortality attributed to short-term PM2·5 exposure were robust.InterpretationShort-term exposure to PM2·5 contributes a substantial global mortality burden, particularly in Asia and Africa, as well as in global urban areas. Our results highlight the importance of mitigation strategies to reduce short-term exposure to air pollution and its adverse effects on human health.FundingAustralian Research Council and the Australian National Health and Medical Research Council.
A reference standard for urinary tract infection research: a multidisciplinary Delphi consensus study
Authors: Manu P Bilsen, Simon P Conroy, Caroline Schneeberger, Tamara N Platteel, Cees van Nieuwkoop, Lona Mody, Jeffrey M Caterino, Suzanne E Geerlings, Bela Köves, Florian Wagenlehner, Marleen Kunneman, Leo G Visser, Merel M C Lambregts, Thomas Hooton, Lindsay Nicolle, Barbara Trautner, Kalpana Gupta, Dimitri Drekonja, Angela Huttner, Laila Schneidewind, Truls Erik Bjerklund Johansen, José Medina-Polo, Jennifer Kranz, Thijs Ten Doesschate, Alewijn Ott, Sacha Kuil, Michael Pulia, Veronica Nwagwu, Christopher Carpenter, Andrew Russel, Janneke Stalenhoef, Sophie Clark, Lauren Southerland, Daan Notermans, Brynjar Fure, Evert Baten, Sean Ninan, Lara Gerbrandy-Schreuders, Karlijn Van Halem, Marco Blanker, Kurt Naber, Adrian Pilatz, Stefan Heytens, Ali Vahedi, David Talan, Ed Kuijper, Jaap Van Dissel, Jochen Cals, Sarah Dubbs, Rajan Veeratterapillay, Pär-Daniel Sundvall, Silvia Bertagnolio, Christopher Graber, Wouter Rozemeijer, Robin Jump, Ildiko Gagyor, Ingvild Vik, Karola Waar, Martha Van der Beek
Journal: The Lancet Infectious Diseases (2024)
Non-opioid analgesic combinations following total hip arthroplasty (RECIPE): a randomised, placebo-controlled, blinded, multicentre trial
Authors: Joakim Steiness, Daniel Hägi-Pedersen, Troels Haxholdt Lunn, Søren Overgaard, Stig Brorson, Ben Kristian Graungaard, Martin Lindberg-Larsen, Claus Varnum, Lars Hyldborg Lundstrøm, Torben Beck, Michael Skettrup, Niels Anker Pedersen, Manuel Josef Bieder, Adam Gregers von Cappeln, Lina Pleckaitiene, Peter Lindholm, Syed Shaheer Haider Bukhari, Cecilie Bauer Derby, Maria Gantzel Nielsen, Oskar Wilborg Exsteen, Louise Ørts Vinstrup, Kasper Højgaard Thybo, Kasper Smidt Gasbjerg, Anders Kehlet Nørskov, Janus Christian Jakobsen, Ole Mathiesen
Journal: The Lancet Rheumatology (2024)
Environmental assessment of diets: overview and guidance on indicator choice
Authors: Ylva Ran, Christel Cederberg, Malin Jonell, Kristina Bergman, Imke J M De Boer, Rasmus Einarsson, Johan Karlsson, Hanna Karlsson Potter, Michael Martin, Geneviève S Metson, Thomas Nemecek, Kimberly A Nicholas, Åsa Strand, Pernilla Tidåker, Hayo Van der Werf, Davy Vanham, Hannah H E Van Zanten, Francesca Verones, Elin Röös
Journal: The Lancet Planetary Health (2024)

Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information. This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets. We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and private-sector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consumption, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environmental trade-offs. If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
Duet of humoral and cellular immunity for conquering HCV
Authors: Hosun Yu, Eui-Cheol Shin
Journal: Hepatology (2024)

1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science, and Technology (KAIST), Daejeon 34141, Republic of Korea 2The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea Correspondence Eui-Cheol Shin, The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea. Email: [email protected]
Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts
Authors: Elyse A. Olesinski, Karanpreet Singh Bhatia, Chuqi Wang, Marissa S. Pioso, Xiao Xian Lin, Ahmed M. Mamdouh, Shu Xuan Ng, Vedant Sandhu, Shaista Shabbir Jasdanwala, Binyam Yilma, Stephan Bohl, Jeremy A. Ryan, Disha Malani, Marlise R. Luskin, Olli Kallioniemi, Kimmo Porkka, Sophia Adamia, Wee Joo Chng, Motomi Osato, David M. Weinstock, Jacqueline S. Garcia, Anthony Letai, Shruti Bhatt
Journal: Blood Cancer Discovery (2024)

Abstract In many cancers, mortality is associated with the emergence of relapse with multidrug resistance (MDR). Thus far, the investigation of cancer relapse mechanisms has largely focused on acquired genetic mutations. Using acute myeloid leukemia (AML) patient-derived xenografts (PDX), we systematically elucidated a basis of MDR and identified drug sensitivity in relapsed AML. We derived pharmacologic sensitivity for 22 AML PDX models using dynamic BH3 profiling (DBP), together with genomics and transcriptomics. Using in vivo acquired resistant PDXs, we found that resistance to unrelated, narrowly targeted agents in distinct PDXs was accompanied by broad resistance to drugs with disparate mechanisms. Moreover, baseline mitochondrial apoptotic priming was consistently reduced regardless of the class of drug-inducing selection. By applying DBP, we identified drugs showing effective in vivo activity in resistant models. This study implies evasion of apoptosis drives drug resistance and demonstrates the feasibility of the DBP approach to identify active drugs for patients with relapsed AML. Significance: Acquired resistance to targeted therapy remains challenging in AML. We found that reduction in mitochondrial priming and common transcriptomic signatures was a conserved mechanism of acquired resistance across different drug classes in vivo. Drugs active in vivo can be identified even in the multidrug resistant state by DBP.
Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy
Authors: Danira Toral-Rios, Justin M. Long, Jason D. Ulrich, Jinsheng Yu, Michael R. Strickland, Xianlin Han, David M. Holtzman, Anil G. Cashikar, Steven M. Paul
Journal: The Journal of Experimental Medicine (2024)

Alzheimer’s disease (AD) is characterized by amyloid plaques and neurofibrillary tangles, in addition to neuroinflammation and changes in brain lipid metabolism. 25-Hydroxycholesterol (25-HC), a known modulator of both inflammation and lipid metabolism, is produced by cholesterol 25-hydroxylase encoded by Ch25h expressed as a “disease-associated microglia” signature gene. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown. Here, we show that in the absence of Ch25h and the resultant reduction in 25-HC, there is strikingly reduced age-dependent neurodegeneration and neuroinflammation in the hippocampus and entorhinal/piriform cortex of PS19 mice, which express the P301S mutant human tau transgene. Transcriptomic analyses of bulk hippocampal tissue and single nuclei revealed that Ch25h deficiency in PS19 mice strongly suppressed proinflammatory signaling in microglia. Our results suggest a key role for Ch25h/25-HC in potentiating proinflammatory signaling to promote tau-mediated neurodegeneration. Ch25h may represent a novel therapeutic target for primary tauopathies, AD, and other neuroinflammatory diseases.
Association Between Immediate Treatment of Early Gestational Diabetes Mellitus and Breastfeeding Outcomes: Findings From the TOBOGM Study
Authors: Canaan Negash Seifu, Jincy Immanuel, William M. Hague, Helena Teede, N. Wah Cheung, Emily J. Hibbert, Christopher J. Nolan, Michael J. Peek, Vincent W. Wong, Jeff R. Flack, Mark McLean, Arianne Sweeting, Alexandra Kautzky-Willer, Jürgen Harreiter, Emily Gianatti, Viswanathan Mohan, Helena Backman, David Simmons, David Simmons, N. Wah Cheung, Jincy Immanuel, William M. Hague, Helena Teede, Christopher J. Nolan, Michael J. Peek, Jeff R. Flack, Mark McLean, Vincent Wong, Emily Hibbert, Emily Gianatti, Arianne Sweeting, Suzette Coat, Raiyomand Dalal, Georgia Soldatos, Suja Padmanabhan, Rohit Rajagopal, Victoria Rudland, Jürgen Harreiter, Alexandra Kautzky-Willer, Herbert Kiss, Helena Backman, Erik Schwarcz, Glynis Ross, Viswanathan Mohan, Ranjit Mohan Anjana, Uma Ram
Journal: Diabetes Care (2024)
Reply: Provider preparedness for functional cure of chronic hepatitis B
Authors: Jessica Howell, Margaret E. Hellard
Journal: Hepatology (2024)

We thank Professor Perillo and Professor Janssens for their interest in our review article, which outlined the steps needed for global hepatitis B elimination and future cure preparedness. We agree with their excellent points regarding the need for hepatitis B cure preparedness among the hepatology specialist community, as well as nonspecialists and primary care. The complexity of emerging new treatment regimens and the off-target effects of these agents will necessitate liver specialist care. Hepatology nurse specialists will have an essential role in the delivery of these complex functional cure regimens and in facilitating the efficient linkage of people eligible for hepatitis B cure into specialist care. However, as familiarity with these agents expands and safer, simpler iterations of initial curative regimens are developed over time, the scope of practitioners who are able to provide curative treatment is likely to expand. Efficient systems that enable rapid identification of people living with chronic hepatitis B in primary and tertiary care and link them to specialist hepatology care will be critical to ensure effective roll-out of future cures; these systems should be developed in partnership with affected communities now. Community organizations, peers, and integrated nurses will have a vital role to play in linking people to cure, particularly as treatment eligibility expands. Improving hepatitis B vaccination coverage globally will also reduce the urgency for treatment-as-prevention by driving a decline in the number of people at risk of hepatitis B. While delivery of complex hepatitis B curative regimens in low-resource and remote settings will remain a major challenge: there is still much to be done to improve diagnosis: linkage to care, and uptake of nucleos(t)ide analog therapy. This includes simplifying current hepatitis B management guidelines to facilitate decentralized nucleos(t)ide analog therapy delivery in primary care. By striving to achieve World Health Organization 2030 hepatitis B elimination targets, the world will also be preparing for hepatitis B cure.