tbuckley/cabot-search huggingface dataset:
Human determinants of age-dependent patterns of death from infection
Authors: Laurent Abel, Jean-Laurent Casanova
Journal: Immunity (2024)

Regardless of microbial virulence (i.e., the global infection-fatality ratio), age generally drives the prevalence of death from infection in unvaccinated humans. Four mortality patterns are recognized: the common U- and L-shaped curves of endemic infections and the unique W- and J-shaped curves of pandemic infections. We suggest that these patterns result from different sets of human genetic and immunological determinants. In this model, it is the interplay between (1) monogenic genotypes affecting immunity to primary infection that preferentially manifest early in life and related genotypes or their phenocopies, including auto-antibodies, which manifest later in life and (2) the occurrence and persistence of adaptive, acquired immunity to primary or cross-reactive infections, which shapes the age-dependent pattern of human deaths from infection.
Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B
Authors: Jian-Wei Zhang, Rui-Min Lai, Long-Fei Wang, Si-Ling Wang, Han-Xin Xue, Chen Li, Zi-Zheng Zheng, Jie Li, Yue-Yong Zhu, Da-Wu Zeng, Jing Chen, Qi-Shui Ou, Tian-Bin Chen, Zhen Xun, Jia-Ji Jiang, Qi Zheng
Journal: Journal of Hepatology (2024)
Translational Aspects of 3D and 4D Printing and Bioprinting
Authors: Scott Taylor, Eva Mueller, Lamont R. Jones, Ashley V. Makela, Nureddin Ashammakhi
Journal: Advanced Healthcare Materials (2024)

Abstract Three‐dimensional (3D) printed medical devices include orthopedic and craniofacial implants, surgical tools, and external prosthetics that have been directly used in patients. While the advances of additive manufacturing techniques in the production of medical devices have been on the rise, clinical translation of living cellular constructs face significant limitations in terms of regulatory affairs, process technology, and materials development. In this perspective, the current status‐quo of 3D and four‐dimensional (4D) (bio)printing is summarized, current advancements are discussed and the challenges that need to be addressed for improved industrial translation and clinical applications of bioprinting are highlighted. It is focused on a multidisciplinary approach in discussing the key translational considerations, from the perspective of industry, regulatory bodies, funding strategies, and future directions.
Seasonal malaria chemoprevention and the spread of Plasmodium falciparum quintuple-mutant parasites resistant to sulfadoxine–pyrimethamine: a modelling study
Authors: Thiery Masserey, Tamsin Lee, Sherrie L Kelly, Ian M Hastings, Melissa A Penny
Journal: The Lancet Microbe (2024)

Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine prevents millions of clinical malaria cases in children younger than 5 years in Africa's Sahel region. However, Plasmodium falciparum parasites partially resistant to sulfadoxine-pyrimethamine (with quintuple mutations) potentially threaten the protective effectiveness of SMC. We evaluated the spread of quintuple-mutant parasites and the clinical consequences.
Spatiotemporally Controllable Covalent Bonding of RNA for Multi‐Protein Interference
Authors: Hao Fang, Tingting Wang, Jun Dai, Jing‐Jing Hu, Zhaojun Chen, Lizhen Yuan, Yuning Hong, Fan Xia, Xiaoding Lou
Journal: Advanced Healthcare Materials (2024)

Many diseases are associated with genetic mutation and expression of mutated proteins, such as cancers. Therapeutic approaches that selectively target the synthesis process of multiple proteins show greater potential compared to single-protein approaches in oncological diseases. However, conventional agents to regulate the synthesis of multiple protein still suffer from poor spatiotemporal selectivity and stability. Here, a new method using a dye-peptide conjugate, PRFK, for multi-protein interference with spatiotemporal selectivity and reliable stability, is reported. By using the peptide sequence that targets tumor cells, PRFK can be efficiently taken up, followed by specific binding to the KDELR (KDEL receptor) protein located in the endoplasmic reticulum (ER). The dye generates
Therapeutic avenues in bone repair: Harnessing an anabolic osteopeptide, PEPITEM, to boost bone growth and prevent bone loss
Authors: Jonathan W. Lewis, Kathryn Frost, Georgiana Neag, Mussarat Wahid, Melissa Finlay, Ellie H. Northall, Oladimeji Abudu, Samuel Kemble, Edward T. Davis, Emily Powell, Charlotte Palmer, Jinsen Lu, G. Ed Rainger, Asif J. Iqbal, Myriam Chimen, Ansar Mahmood, Simon W. Jones, James R. Edwards, Amy J. Naylor, Helen M. McGettrick
Journal: Cell Reports Medicine (2024)
DNA Tetrahedron Delivering miR‐21‐5p Promotes Senescent Bone Defects Repair through Synergistic Regulation of Osteogenesis and Angiogenesis
Authors: Lei Qi, Shebin Hong, Tong Zhao, Jinge Yan, Weiwen Ge, Jing Wang, Xin Fang, Weidong Jiang, Steve GF Shen, Lei Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Compromised osteogenesis and angiogenesis is the character of stem cell senescence, which brought difficulties for bone defects repairing in senescent microenvironment. As the most abundant bone‐related miRNA, miRNA‐21‐5p plays a crucial role in inducing osteogenic and angiogenic differentiation. However, highly efficient miR‐21‐5p delivery still confronts challenges including poor cellular uptake and easy degradation. Herein, TDN‐miR‐21‐5p nanocomplex is constructed based on DNA tetrahedral (TDN) and has great potential in promoting osteogenesis and alleviating senescence of senescent bone marrow stem cells (O‐BMSCs), simultaneously enhancing angiogenic capacity of senescent endothelial progenitor cells (O‐EPCs). Of note, the activation of AKT and Erk signaling pathway may direct regulatory mechanism of TDN‐miR‐21‐5p mediated osteogenesis and senescence of O‐BMSCs. Also, TDN‐miR‐21‐5p can indirectly mediate osteogenesis and senescence of O‐BMSCs through pro‐angiogenic growth factors secreted from O‐EPCs. In addition, gelatin methacryloyl (GelMA) hydrogels are mixed with TDN and TDN‐miR‐21‐5p to fabricate delivery scaffolds. TDN‐miR‐21‐5p@GelMA scaffold exhibits greater bone repair with increased expression of osteogenic‐ and angiogenic‐related markers in senescent critical‐size cranial defects in vivo. Collectively, TDN‐miR‐21‐5p can alleviate senescence and induce osteogenesis and angiogenesis in senescent microenvironment, which provides a novel candidate strategy for senescent bone repair and widen clinical application of TDNs‐based gene therapy.
Biodistribution and Biotoxicity Assessment of Fluorescent Conjugated Polymer Dots
Authors: Panting Ren, Jingru Li, Liqin Xiong
Journal: Advanced Healthcare Materials (2024)

Conjugated polymer dots (Pdots) have shown potential in the biomedical fields due to their optical properties and customizable design. However, the limited research on the biotoxicity of Pdots hinders their further application and translation. Lipophilic Pdots are prone to adsorbing specific proteins, leading to targeted tissue accumulation. Therefore, lipophilic fluorescent Pdots (Bare-Pdots) are synthesized using the conjugated polymer poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) to systematically evaluate their biodistribution and biotoxicity in stem cells, zebrafish embryos, and mice. It is observed that Bare-Pdots are readily internalized by cells and adhered to the embryonic chorion. Additionally, Bare-Pdots exhibit a distinct distribution in brown adipose tissue and heart, closely associated with phagocytosis of capillary endothelial cells involved in lipid metabolism. Notably, injection of Bare-Pdots at 5 mg kg
Oriented cellulose hydrogel: Directed tissue regeneration for reducing corneal leukoplakia and managing fungal corneal ulcers
Authors: Lina Dong, Zixin Fan, Bixing Fang, Xiaoyu Zhao, Hongyi Yao, Gangpei Cai, Shuo Yang, Guoming Zhang, Xiaoqi Cheng, Yun Feng, Shengli Mi, Wei Sun
Journal: Bioactive Materials (2024)

Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries. Corneal scars such as leukoplakia are formed due to inflammation, oxidative stress and non-directed repair, which seriously affect the patients' subsequent visual and life quality. In this study, drawing inspiration from the oriented structure of collagen fibers within the corneal stroma, we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning. It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer. The results showed that it effectively inhibited
A General Strategy for Enhanced Photodynamic Antimicrobial Therapy with Perylenequinonoid Photosensitizers Using a Macrocyclic Supramolecular Carrier
Authors: Zekun Gao, Xiuli Zheng, Xiangyu Dong, Weimin Liu, Jie Sha, Shuaishuai Bian, Jian Li, Huan Cong, Chun‐Sing Lee, Pengfei Wang
Journal: Advanced Healthcare Materials (2024)

Abstract Perylenequinonoid natural products are a class of photosensitizers (PSs) that exhibit high reactive oxygen species (ROS) generation and excellent activity for Type I/Type II dual photodynamic therapy. However, their limited activity against gram‐negative bacteria and poor water solubility significantly restrict their potential in broad‐spectrum photodynamic antimicrobial therapy (PDAT). Herein, a general approach to overcome the limitations of perylenequinonoid photosensitizers (PQPSs) in PDAT by utilizing a macrocyclic supramolecular carrier is presented. Specifically, AnBox·4Cl, a water‐soluble cationic cyclophane, is identified as a universal macrocyclic host for PQPSs such as elsinochrome C, hypocrellin A, hypocrellin B, and hypericin, forming 1:1 host–guest complexes with high binding constants (≈10 7 m −1 ) in aqueous solutions. Each AnBox·4Cl molecule carries four positive charges that promote strong binding with the membrane of gram‐negative bacteria. As a result, the AnBox·4Cl‐PQPS complexes can effectively anchor on the surfaces of gram‐negative bacteria, while the PQPSs alone cannot. In vitro and in vivo experiments demonstrate that these supramolecular PSs have excellent water solubility and high ROS generation, with broad‐spectrum PDAT effect against both gram‐negative and gram‐positive bacteria. This work paves a new path to enhance PDAT by showcasing an efficient approach to improve PQPSs’ water solubility and killing efficacy for gram‐negative bacteria.
Surveillance for Violent Deaths — National Violent Death Reporting System, 48 States, the District of Columbia, and Puerto Rico, 2021
Authors: Brenda L. Nguyen, Bridget H. Lyons, Kaitlin Forsberg, Rebecca F. Wilson, Grace S. Liu, Carter J. Betz, Janet M. Blair
Journal: MMWR Surveillance Summaries (2024)

Problem/Condition: In 2021, approximately 75,000 persons died of violence-related injuries in the United States.This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) on violent deaths that occurred in 48 states, the District of Columbia, and Puerto Rico in 2021.Results are reported by sex, age group, race and ethnicity, method of injury, type of location where the injury occurred, circumstances of injury, and other selected characteristics.This report introduces additional incident and circumstance variables, which now include child victim-specific circumstance information.This report also incorporates new U.S. Census Bureau race and ethnicity categories, which now account for more than one race and Native Hawaiian or other Pacific Islander categories and include updated denominators to calculate rates for these populations.
Signals behind <i>Listeria monocytogenes</i> virulence mechanisms
Authors: Diana Meireles, Rita Pombinho, Didier Cabanes
Journal: Gut Microbes (2024)

The tight and coordinated regulation of virulence gene expression is crucial to ensure the survival and persistence of bacterial pathogens in different contexts within their hosts. Considering this, bacteria do not express virulence factors homogenously in time and space, either due to their associated fitness cost or to their detrimental effect at specific infection stages. To efficiently infect and persist into their hosts, bacteria have thus to monitor environmental cues or chemical cell-to-cell signaling mechanisms that allow their transition from the external environment to the host, and therefore adjust gene expression levels, intrinsic biological activities, and appropriate behaviors. Listeria monocytogenes (Lm), a major Gram-positive facultative intracellular pathogen, stands out for its adaptability and capacity to thrive in a wide range of environments. Because of that, Lm presents itself as a significant concern in food safety and public health, that can lead to potentially life-threatening infections in humans. A deeper understanding of the intricate bacterial virulence mechanisms and the signals that control them provide valuable insights into the dynamic interplay between Lm and the host. Therefore, this review addresses the role of some crucial signals behind Lm pathogenic virulence mechanisms and explores how the ability to assimilate and interpret these signals is fundamental for pathogenesis, identifying potential targets for innovative antimicrobial strategies.
Publisher Correction: MYC activity at enhancers drives prognostic transcriptional programs through an epigenetic switch
Authors: Simon T Jakobsen, Rikke A M Jensen, Maria S Madsen, Tina Ravnsborg, Christian S Vaagenso, Majken S Siersbæk, Hjorleifur Einarsson, Robin Andersson, Ole N Jensen, Rasmus Siersbæk
Journal: Nature Genetics (2024)
Incidence and risk factors of cutaneous reactions to the first COVID‐19 booster vaccine
Authors: Liam R. Smith, Ruchi J. Shah, Andrew J. King, Erica S. Shenoy, Adam B. Landman, Dean M. Hashimoto, Kimberly Blumenthal
Journal: Allergy (2024)

Table S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Antifungal prophylaxis of COVID-19 associated pulmonary aspergillosis in ventilated patients: one solution does not fit all
Authors: Juergen Prattes, Daniele R. Giacobbe, Matteo Bassetti, Jean-Pierre Gangneux, Martin Hoenigl, Cristina Marelli, Alessio Signori, Silvia Dettori, Greta Cattardico, Jonas Frost, Florian Reizine
Journal: Intensive Care Medicine (2024)
A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression
Authors: Weiwei Liu, Zhao Ding, Ye Tao, Shixian Liu, Maoyu Jiang, Fangzheng Yi, Zixi Wang, Yanxun Han, Huaiyuan Zong, Dapeng Li, Yue Zhu, Zihui Xie, Shujia Sang, Xixi Chen, Manli Miao, Xu Chen, Wei Lin, Yi Zhao, Guibin Zheng, Mark Zafereo, Guojun Li, Jing Wu, Xiaojun Zha, Yehai Liu
Journal: Molecular Cancer (2024)

Abstract Background The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. Methods We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. Results Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. Conclusion Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.
Reaction severity and peach threshold amount during oral challenge in nonspecific lipid transfer protein allergy
Authors: Natalia Pérez‐Sánchez, Carmen Rondón, José Antonio Cañas, Rocío Sáenz de Santa María‐García, Julia Rodríguez, Marta Andugar‐Moreno, Cristobalina Mayorga, María José Torres, Francisca Gómez
Journal: Allergy (2024)

Figure S1. Figure S2. Figure S3. Figure S4. Table S1. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cardiovascular disease in adults with a history of out-of-home care during childhood: a systematic review and meta-analysis of prospective cohort studies
Authors: G David Batty, Mika Kivimäki, Ylva B Almquist, Johan G Eriksson, Mika Gissler, Emmanuel S Gnanamanickam, Mark Hamer, Josephine Jackisch, Hee-Soon Juon, Markus Keski-Säntti, Chaiquan Li, Tuija M Mikkola, Emily Murray, Amanda Sacker, Leonie Segal, Philipp Frank
Journal: The Lancet Regional Health - Europe (2024)
Construction of Iron‐Scavenging Hydrogel via Thiol–Ene Click Chemistry for Antibiotic‐Free Treatment of Bacterial Wound Infection
Authors: Tian‐Qiu Xie, Xiao Yan, Jian‐Hua Yan, Yun‐Jian Yu, Xin‐Hua Liu, Jun Feng, Chuan‐Jun Liu, Xian‐Zheng Zhang
Journal: Advanced Healthcare Materials (2024)

Bacteria, especially drug-resistant strains, can quickly cause wound infections, leading to delayed healing and fatal risk in clinics. With the growing need for alternative antibacterial approaches that rely less on antibiotics or eliminate their use altogether, a novel antibacterial hydrogel named Ovtgel is developed. Ovtgel is formulated by chemically crosslinking thiol-modified ovotransferrin (Ovt), a member of the transferrin family found in egg white, with olefin-modified agarose through thiol-ene click chemistry. Ovt is designed to sequester ferric ions essential for bacterial survival and protect wound tissues from damages caused by the reactive oxygen species (ROS) generated in Fenton reactions. Experimental data have shown that Ovtgel significantly enhances wound healing by inhibiting bacterial growth and shielding tissues from ROS-induced harms. Unlike traditional antibiotics, Ovtgel targets essential trace elements required for bacterial survival in the host environment, preventing the development of drug resistance in pathogenic bacteria. Ovtgel exhibits excellent biocompatibility due to the homology of Ovt to mammalian transferrin. This hydrogel has the potential to serve as an effective antibiotic-free solution for combating bacterial infections.
Paravertebrally‐Injected Multifunctional Hydrogel for Sustained Anti‐Inflammation and Pain Relief in Lumbar Disc Herniation
Authors: Wenhao Deng, Jianpeng Chen, Xinli Wang, Qianliang Wang, Lei Zhao, Yuzheng Zhu, Jun Yan, Yiran Zheng
Journal: Advanced Healthcare Materials (2024)

Abstract Pain caused by lumbar disc herniation (LDH) severely compromises patients’ quality of life. The combination of steroid and local anesthetics is routinely employed in clinics to alleviate LDH‐induced pain. However, the approach only mediates transient efficacy and requires repeated and invasive lumbar epidural injections. Here a paravertebrally‐injected multifunctional hydrogel that can efficiently co‐load and controlled release glucocorticoid betamethasone and anesthetics ropivacaine for sustained anti‐inflammation, reactive oxygen species (ROS)‐removal and pain relief in LDH is presented. Betamethasone is conjugated to hyaluronic acid (HA) via ROS‐responsive crosslinker to form amphiphilic polymer that self‐assemble into particles with ropivacaine loaded into the core. Solution of drug‐loaded particles and thermo‐sensitive polymer rapidly forms therapeutic hydrogel in situ upon injection next to the herniated disc, thus avoiding invasive epidural injection. In a rat model of LDH, multifunctional hydrogel maintains the local drug concentration 72 times longer than free drugs and more effectively inhibits the expression of pro‐inflammatory cytokines and pain‐related molecules including cyclooxygenase‐2 (COX‐2) and prostaglandin E2 (PGE 2 ). Therapeutic hydrogel suppresses the LDH‐induced pain in rats for 12 days while the equivalent dose of free drugs is only effective for 3 days. This platform is also applicable to ameliorate pain caused by other spine‐related diseases.
Flexible multitask computation in recurrent networks utilizes shared dynamical motifs
Authors: Laura N. Driscoll, Krishna Shenoy, David Sussillo
Journal: Nature Neuroscience (2024)

Abstract Flexible computation is a hallmark of intelligent behavior. However, little is known about how neural networks contextually reconfigure for different computations. In the present work, we identified an algorithmic neural substrate for modular computation through the study of multitasking artificial recurrent neural networks. Dynamical systems analyses revealed learned computational strategies mirroring the modular subtask structure of the training task set. Dynamical motifs, which are recurring patterns of neural activity that implement specific computations through dynamics, such as attractors, decision boundaries and rotations, were reused across tasks. For example, tasks requiring memory of a continuous circular variable repurposed the same ring attractor. We showed that dynamical motifs were implemented by clusters of units when the unit activation function was restricted to be positive. Cluster lesions caused modular performance deficits. Motifs were reconfigured for fast transfer learning after an initial phase of learning. This work establishes dynamical motifs as a fundamental unit of compositional computation, intermediate between neuron and network. As whole-brain studies simultaneously record activity from multiple specialized systems, the dynamical motif framework will guide questions about specialization and generalization.
Sensing and guiding cell-state transitions by using genetically encoded endoribonuclease-mediated microRNA sensors
Authors: Lei Wang, Wenlong Xu, Shun Zhang, Gregory C Gundberg, Christine R Zheng, Zhengpeng Wan, Kamila Mustafina, Fabio Caliendo, Hayden Sandt, Roger Kamm, Ron Weiss
Journal: Nature Biomedical Engineering (2024)