tbuckley/cabot-search huggingface dataset:
Acetyl-CoA carboxylase obstructs CD8+ T cell lipid utilization in the tumor microenvironment
Authors: Elizabeth G. Hunt, Katie E. Hurst, Brian P. Riesenberg, Andrew S. Kennedy, Evelyn J. Gandy, Alex M. Andrews, Coral del Mar Alicea Pauneto, Lauren E. Ball, Emily D. Wallace, Peng Gao, Jeremy Meier, Jonathan S. Serody, Michael F. Coleman, Jessica E. Thaxton
Journal: Cell Metabolism (2024)

The solid tumor microenvironment (TME) imprints a compromised metabolic state in tumor-infiltrating T cells (TILs), hallmarked by the inability to maintain effective energy synthesis for antitumor function and survival. T cells in the TME must catabolize lipids via mitochondrial fatty acid oxidation (FAO) to supply energy in nutrient stress, and it is established that T cells enriched in FAO are adept at cancer control. However, endogenous TILs and unmodified cellular therapy products fail to sustain bioenergetics in tumors. We reveal that the solid TME imposes perpetual acetyl-coenzyme A (CoA) carboxylase (ACC) activity, invoking lipid biogenesis and storage in TILs that opposes FAO. Using metabolic, lipidomic, and confocal imaging strategies, we find that restricting ACC rewires T cell metabolism, enabling energy maintenance in TME stress. Limiting ACC activity potentiates a gene and phenotypic program indicative of T cell longevity, engendering T cells with increased survival and polyfunctionality, which sustains cancer control.
Impaired skeletal muscle regeneration in diabetes: From cellular and molecular mechanisms to novel treatments
Authors: Ever Espino-Gonzalez, Emilie Dalbram, Rémi Mounier, Julien Gondin, Jean Farup, Niels Jessen, Jonas T. Treebak
Journal: Cell Metabolism (2024)

Diabetes represents a major public health concern with a considerable impact on human life and healthcare expenditures. It is now well established that diabetes is characterized by a severe skeletal muscle pathology that limits functional capacity and quality of life. Increasing evidence indicates that diabetes is also one of the most prevalent disorders characterized by impaired skeletal muscle regeneration, yet underlying mechanisms and therapeutic treatments remain poorly established. In this review, we describe the cellular and molecular alterations currently known to occur during skeletal muscle regeneration in people with diabetes and animal models of diabetes, including its associated comorbidities, e.g., obesity, hyperinsulinemia, and insulin resistance. We describe the role of myogenic and non-myogenic cell types on muscle regeneration in conditions with or without diabetes. Therapies for skeletal muscle regeneration and gaps in our knowledge are also discussed, while proposing future directions for the field.
Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants
Authors: Timothy S. Johnston, Shuk Hang Li, Mark M. Painter, Reilly K. Atkinson, Naomi R. Douek, David B. Reeg, Daniel C. Douek, E. John Wherry, Scott E. Hensley
Journal: Immunity (2024)
Long-lasting mRNA-encoded interleukin-2 restores CD8+ T cell neoantigen immunity in MHC class I-deficient cancers
Authors: Jan D. Beck, Mustafa Diken, Martin Suchan, Michael Streuber, Elif Diken, Laura Kolb, Lisa Allnoch, Fulvia Vascotto, Daniel Peters, Tim Beißert, Özlem Akilli-Öztürk, Özlem Türeci, Sebastian Kreiter, Mathias Vormehr, Ugur Sahin
Journal: Cancer Cell (2024)
BSAlign: A Library for Nucleotide Sequence Alignment
Authors: Haojing Shao, Jue Ruan
Journal: Genomics Proteomics & Bioinformatics (2024)

Increasing the accuracy of the nucleotide sequence alignment is an essential issue in genomics research. Although classic dynamic programming (DP) algorithms (e.g., Smith-Waterman and Needleman-Wunsch) guarantee to produce the optimal result, their time complexity hinders the application of large-scale sequence alignment. Many optimization efforts that aim to accelerate the alignment process generally come from three perspectives: redesigning data structures [e.g., diagonal or striped Single Instruction Multiple Data (SIMD) implementations], increasing the number of parallelisms in SIMD operations (e.g., difference recurrence relation), or reducing search space (e.g., banded DP). However, no methods combine all these three aspects to build an ultra-fast algorithm. In this study, we developed a Banded Striped Aligner (BSAlign) library that delivers accurate alignment results at an ultra-fast speed by knitting a series of novel methods together to take advantage of all of the aforementioned three perspectives with highlights such as active F-loop in striped vectorization and striped move in banded DP. We applied our new acceleration design on both regular and edit distance pairwise alignment. BSAlign achieved 2-fold speed-up than other SIMD-based implementations for regular pairwise alignment, and 1.5-fold to 4-fold speed-up in edit distance-based implementations for long reads. BSAlign is implemented in C programing language and is available at https://github.com/ruanjue/bsalign.
Ferried Albumin‐Inspired Bioadhesive With Dynamic Interfacial Bonds for Emergency Rescue
Authors: Yiming Chen, Huiying Li, Renfeng Xu, Yan Fang, Qinhui Chen, Zhengchao Wang, Haiqing Liu, Yunxiang Weng
Journal: Advanced Healthcare Materials (2024)

Emergency prehospital wound closure and hemorrhage control are the first priorities for life-saving. Majority of bioadhesives form bonds with tissues through irreversible cross-linking, and the remobilization of misalignment may cause severe secondary damage to tissues. Therefore, developing an adhesive that can quickly and tolerably adhere to traumatized dynamic tissue or organ surfaces in emergency situations is a major challenge. Inspired by the structure of human serum albumin (HSA), a branched polymer with multitentacled sulfhydryl is synthesized, then, an instant and fault-tolerant tough wet-tissue adhesion (IFA) hydrogel is prepared. Adhesive application time is just 5 s (interfacial toughness of ≈580 J m
Enhancing healthy aging with small molecules: A mitochondrial perspective
Authors: Xiujiao Qin, Hongyuan Li, Huiying Zhao, Le Fang, Xiaohui Wang
Journal: Medicinal Research Reviews (2024)

The pursuit of enhanced health during aging has prompted the exploration of various strategies focused on reducing the decline associated with the aging process. A key area of this exploration is the management of mitochondrial dysfunction, a notable characteristic of aging. This review sheds light on the crucial role that small molecules play in augmenting healthy aging, particularly through influencing mitochondrial functions. Mitochondrial oxidative damage, a significant aspect of aging, can potentially be lessened through interventions such as coenzyme Q10, alpha-lipoic acid, and a variety of antioxidants. Additionally, this review discusses approaches for enhancing mitochondrial proteostasis, emphasizing the importance of mitochondrial unfolded protein response inducers like doxycycline, and agents that affect mitophagy, such as urolithin A, spermidine, trehalose, and taurine, which are vital for sustaining protein quality control. Of equal importance are methods for modulating mitochondrial energy production, which involve nicotinamide adenine dinucleotide boosters, adenosine 5'-monophosphate-activated protein kinase activators, and compounds like metformin and mitochondria-targeted tamoxifen that enhance metabolic function. Furthermore, the review delves into emerging strategies that encourage mitochondrial biogenesis. Together, these interventions present a promising avenue for addressing age-related mitochondrial degradation, thereby setting the stage for the development of innovative treatment approaches to meet this extensive challenge.
Nasal allergen‐neutralizing antibodies correlate closely with tolerated intranasal allergen challenge dose following grass pollen subcutaneous immunotherapy in patients with local allergic rhinitis
Authors: Ibon Eguiluz‐Gracia, Rebecca V. Parkin, Janice A. Layhadi, Elizabeth Palmer, Xun Meng, Rongfei Zhu, Umit Sahiner, Stephen R. Durham, Maria Jose Torres, Cristobalina Mayorga, Carmen Rondon, Mohamed H. Shamji
Journal: Allergy (2024)

Local allergic rhinitis (LAR) is defined by chronic nasal symptoms, absence of atopy, positive nasal allergen challenge (NAC) and a good response to subcutaneous allergen immunotherapy (SCIT). We sought to investigate SCIT capacity to induce local and systemic blocking antibodies in LAR patients.
Multi-omics provide insights into the regulation of DNA methylation in pear fruit metabolism
Authors: Chao Gu, Mao-Song Pei, Zhi-Hua Guo, Lei Wu, Kai-Jie Qi, Xue-Ping Wang, Hong Liu, Zhongchi Liu, Zhaobo Lang, Shaoling Zhang
Journal: Genome biology (2024)

Abstract Background Extensive research has been conducted on fruit development in crops, but the metabolic regulatory networks underlying perennial fruit trees remain poorly understood. To address this knowledge gap, we conduct a comprehensive analysis of the metabolome, proteome, transcriptome, DNA methylome, and small RNAome profiles of pear fruit flesh at 11 developing stages, spanning from fruitlet to ripening. Here, we systematically investigate the metabolic landscape and regulatory network involved. Results We generate an association database consisting of 439 metabolites and 14,399 genes to elucidate the gene regulatory network of pear flesh metabolism. Interestingly, we detect increased DNA methylation in the promoters of most genes within the database during pear flesh development. Application of a DNA methylation inhibitor to the developing fruit represses chlorophyll degradation in the pericarp and promotes xanthophyll, β-carotene, and abscisic acid (ABA) accumulation in the flesh. We find the gradual increase in ABA production during pear flesh development is correlated with the expression of several carotenoid pathway genes and multiple transcription factors. Of these transcription factors, the zinc finger protein PbZFP1 is identified as a positive mediator of ABA biosynthesis in pear flesh. Most ABA pathway genes and transcription factors are modified by DNA methylation in the promoters, although some are induced by the DNA methylation inhibitor. These results suggest that DNA methylation inhibits ABA accumulation, which may delay fruit ripening. Conclusion Our findings provide insights into epigenetic regulation of metabolic regulatory networks during pear flesh development, particularly with regard to DNA methylation.
The Cass Review: Cis-supremacy in the UK’s approach to healthcare for trans children
Authors: Cal Horton
Journal: International Journal of Transgender Health (2024)

Background Since 2016 trans people in the UK, and particularly trans children, have experienced a sustained and escalating campaign to roll back trans freedoms, rights and access to healthcare. A series of legislative, politicized and media-driven campaigns have resulted in the year-by-year worsening of access to affirmative healthcare for trans children in the UK.
Field testing the transferability of behavioural science knowledge on promoting vaccinations
Authors: Silvia Saccardo, Hengchen Dai, Maria A. Han, Sitaram Vangala, Juyea Hoo, Jeffrey Fujimoto
Journal: Nature Human Behaviour (2024)

As behavioural science is increasingly adopted by organizations, there is a growing need to assess the robustness and transferability of empirical findings. Here, we investigate the transferability of insights from various sources of behavioural science knowledge to field settings. Across three pre-registered randomized controlled trials (RCTs, N = 314,824) involving a critical policy domain-COVID-19 booster uptake-we field tested text-based interventions that either increased vaccinations in prior field work (RCT1, NCT05586204), elevated vaccination intentions in an online study (RCT2, NCT05586178) or were favoured by scientists and non-experts (RCT3, NCT05586165). Despite repeated exposure to COVID-19 vaccination messaging in our population, reminders and psychological ownership language increased booster uptake, replicating prior findings. However, strategies deemed effective by prediction or intention surveys, such as encouraging the bundling of COVID-19 boosters and flu shots or addressing misconceptions, yielded no detectable benefits over simple reminders. These findings underscore the importance of testing interventions' transferability to real-world settings.
Antibody-independent protection against heterologous SARS-CoV-2 challenge conferred by prior infection or vaccination
Authors: Valeria Fumagalli, Micol Ravà, Davide Marotta, Pietro Di Lucia, Elisa B. Bono, Leonardo Giustini, Federica De Leo, Maura Casalgrandi, Emanuele Monteleone, Violette Mouro, Chiara Malpighi, Chiara Perucchini, Marta Grillo, Sara De Palma, Lorena Donnici, Silvia Marchese, Matteo Conti, Hiromi Muramatsu, Stanley Perlman, Norbert Pardi, Mirela Kuka, Raffaele De Francesco, Marco E. Bianchi, Luca G. Guidotti, Matteo Iannacone
Journal: Nature Immunology (2024)

Abstract Vaccines have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality, yet emerging variants challenge their effectiveness. The prevailing approach to updating vaccines targets the antibody response, operating under the presumption that it is the primary defense mechanism following vaccination or infection. This perspective, however, can overlook the role of T cells, particularly when antibody levels are low or absent. Here we show, through studies in mouse models lacking antibodies but maintaining functional B cells and lymphoid organs, that immunity conferred by prior infection or mRNA vaccination can protect against SARS-CoV-2 challenge independently of antibodies. Our findings, using three distinct models inclusive of a novel human/mouse ACE2 hybrid, highlight that CD8 + T cells are essential for combating severe infections, whereas CD4 + T cells contribute to managing milder cases, with interferon-γ having an important function in this antibody-independent defense. These findings highlight the importance of T cell responses in vaccine development, urging a broader perspective on protective immunity beyond just antibodies.
Self-help mobile messaging intervention for depression among older adults in resource-limited settings: a randomized controlled trial
Authors: Marcia Scazufca, Carina Akemi Nakamura, Nadine Seward, Thiago Vinicius Nadaleto Didone, Felipe Azevedo Moretti, Marcelo Oliveira da Costa, Caio Hudson Queiroz de Souza, Gabriel Macias de Oliveira, Monica Souza dos Santos, Luara Aragoni Pereira, Mariana Mendes de Sá Martins, Pepijn van de Ven, William Hollingworth, Tim J. Peters, Ricardo Araya
Journal: Nature Medicine (2024)

Abstract Scalable solutions to treat depression in older adults in low-resourced settings are urgently needed. The PRODIGITAL-D pragmatic, single-blind, two-arm, individually randomized controlled trial assessed the effectiveness of a mobile messaging psychosocial intervention in improving depressive symptomatology among older adults in socioeconomically deprived areas of Guarulhos, Brazil. Older adults (aged 60+ years) registered with 24 primary care clinics and identified with depressive symptomatology (9-item Patient Health Questionnaire (PHQ-9) scores ≥ 10) received the 6-week Viva Vida intervention based on psychoeducation and behavioral activation ( n = 298) or a single message ( n = 305). No health professional support was offered. The primary outcome was improvement from depressive symptomatology (PHQ-9 &lt; 10) at 3 months. Of the 603 participants enrolled (mean age = 65.1 years; 451 (74.8%) women), 527 (87.4%) completed the follow-up assessment. In the intervention arm, 109 of 257 (42.4%) participants had an improved depressive symptomatology, compared with 87 of 270 (32.2%) participants in the control arm (adjusted odds ratio = 1.57; 95% confidence interval = 1.07–2.29; P = 0.019). No severe adverse events related to trial participation were observed. These results demonstrate the usefulness of a digital messaging psychosocial intervention in the short-term improvement from depressive symptomatology that can potentially be integrated into primary care programs for treating older adults with depression. Brazilian Registry of Clinical Trials registration: ReBEC ( RBR-4c94dtn ).
In vivo affinity maturation of mouse B cells reprogrammed to express human antibodies
Authors: Yiming Yin, Yan Guo, Yuxuan Jiang, Brian Quinlan, Haiyong Peng, Gogce Crynen, Wenhui He, Lizhou Zhang, Tianling Ou, Charles C. Bailey, Michael Farzan
Journal: Nature Biomedical Engineering (2024)
Consistency of data reporting in fluid responsiveness studies in the critically ill setting: the CODEFIRE consensus from the Cardiovascular Dynamic section of the European Society of Intensive Care Medicine
Authors: Antonio Messina, Michelle S. Chew, Daniele Poole, Lorenzo Calabrò, Daniel De Backer, Katia Donadello, Glenn Hernandez, Olfa Hamzaoui, Mathieu Jozwiak, Christopher Lai, Manu L. N. G. Malbrain, Jihad Mallat, Sheyla Nainan Myatra, Laurent Muller, Gustavo Ospina-Tascon, Michael R. Pinsky, Sebastian Preau, Bernd Saugel, Jean-Louis Teboul, Maurizio Cecconi, Xavier Monnet
Journal: Intensive Care Medicine (2024)
Zein‐Based Triple‐Drug Nanoparticles to Promote Anti‐Inflammatory Responses for Nerve Regeneration after Spinal Cord Injury
Authors: Jingxuan Wang, Yan Lin, Chunhan Li, Fei Lei, Hongli Luo, Pei Jing, Yao Fu, Zhirong Zhang, Changguang Wang, Zerong Liu, Jun Jiang, Meiling Zhou, Xingjie Du, Zhongbing Liu, Xiangyu Zhou, Xiaoduan Sun, Zhirong Zhong
Journal: Advanced Healthcare Materials (2024)

Defects in autophagy contribute to neurological deficits and motor dysfunction after spinal cord injury. Here a nanosystem is developed to deliver autophagy-promoting, anti-inflammatory drugs to nerve cells in the injured spinal cord. Celastrol, metformin, and everolimus as the mTOR inhibitor are combined into the zein-based nanoparticles, aiming to solubilize the drugs and prolong their circulation. The nanoparticles are internalized by BV2 microglia and SH-SY5Y neuron-like cells in culture; they inhibit the secretion of inflammatory factors by BV2 cells after insult with lipopolysaccharide, and they protect SH-SY5Y cells from the toxicity of H
Concomitant inhibition of the thioredoxin system and nonhomologous DNA repair potently sensitizes Philadelphia‐positive lymphoid leukemia to tyrosine kinase inhibitors
Authors: Lukasz Komorowski, Agnieszka Dabkowska, Joanna Madzio, Agata Pastorczak, Kacper Szczygiel, Martyna Janowska, Klaudyna Fidyt, Maksymilian Bielecki, Jaromir Hunia, Malgorzata Bajor, Tomasz Stoklosa, Magdalena Winiarska, Elzbieta Patkowska, Malgorzata Firczuk
Journal: HemaSphere (2024)

Abstract Breakpoint cluster region‐Abelson ( BCR::ABL1 ) gene fusion is an essential oncogene in both chronic myeloid leukemia (CML) and Philadelphia‐positive (Ph + ) B‐cell acute lymphoblastic leukemia (B‐ALL). While tyrosine kinase inhibitors (TKIs) are effective in up to 95% of CML patients, 50% of Ph + B‐ALL cases do not respond to treatment or relapse. This calls for new therapeutic approaches for Ph + B‐ALL. Previous studies have shown that inhibitors of the thioredoxin (TXN) system exert antileukemic activity against B‐ALL cells, particularly in combination with other drugs. Here, we present that peroxiredoxin‐1 (PRDX1), one of the enzymes of the TXN system, is upregulated in Ph + lymphoid as compared to Ph + myeloid cells. PRDX1 knockout negatively affects the viability of Ph + B‐ALL cells and sensitizes them to TKIs. Analysis of global gene expression changes in imatinib‐treated, PRDX1‐deficient cells revealed that the nonhomologous end‐joining (NHEJ) DNA repair is a novel vulnerability of Ph + B‐ALL cells. Accordingly, PRDX1‐deficient Ph + B‐ALL cells were susceptible to NHEJ inhibitors. Finally, we demonstrated the potent efficacy of a novel combination of TKIs, TXN inhibitors, and NHEJ inhibitors against Ph + B‐ALL cell lines and primary cells, which can be further investigated as a potential therapeutic approach for the treatment of Ph + B‐ALL.
Optical nanomaterial-based detection of biomarkers in liquid biopsy
Authors: Young Jun Kim, Won-Yeop Rho, Seung-min Park, Bong-Hyun Jun
Journal: Journal of Hematology & Oncology (2024)

Abstract Liquid biopsy, which is a minimally invasive procedure as an alternative to tissue biopsy, has been introduced as a new diagnostic/prognostic measure. By screening disease-related markers from the blood or other biofluids, it promises early diagnosis, timely prognostication, and effective treatment of the diseases. However, there will be a long way until its realization due to its conceptual and practical challenges. The biomarkers detected by liquid biopsy, such as circulating tumor cell (CTC) and circulating tumor DNA (ctDNA), are extraordinarily rare and often obscured by an abundance of normal cellular components, necessitating ultra-sensitive and accurate detection methods for the advancement of liquid biopsy techniques. Optical biosensors based on nanomaterials open an important opportunity in liquid biopsy because of their enhanced sensing performance with simple and practical properties. In this review article, we summarized recent innovations in optical nanomaterials to demonstrate the sensitive detection of protein, peptide, ctDNA, miRNA, exosome, and CTCs. Each study prepares the optical nanomaterials with a tailored design to enhance the sensing performance and to meet the requirements of each biomarker. The unique optical characteristics of metallic nanoparticles (NPs), quantum dots, upconversion NPs, silica NPs, polymeric NPs, and carbon nanomaterials are exploited for sensitive detection mechanisms. These recent advances in liquid biopsy using optical nanomaterials give us an opportunity to overcome challenging issues and provide a resource for understanding the unknown characteristics of the biomarkers as well as the mechanism of the disease. Graphical abstract