ResearchPad - health-and-medicine https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Mathematical prediction of clinical outcomes in advanced cancer patients treated with checkpoint inhibitor immunotherapy]]> https://www.researchpad.co/article/elastic_article_7740 We present a mechanistic mathematical model of immune checkpoint inhibitor therapy to address the oncological need for early, broadly applicable readouts (biomarkers) of patient response to immunotherapy. The model is built upon the complex biological and physical interactions between the immune system and cancer, and is informed using only standard-of-care CT. We have retrospectively applied the model to 245 patients from multiple clinical trials treated with anti–CTLA-4 or anti–PD-1/PD-L1 antibodies. We found that model parameters distinctly identified patients with common (n = 18) and rare (n = 10) malignancy types who benefited and did not benefit from these monotherapies with accuracy as high as 88% at first restaging (median 53 days). Further, the parameters successfully differentiated pseudo-progression from true progression, providing previously unidentified insights into the unique biophysical characteristics of pseudo-progression. Our mathematical model offers a clinically relevant tool for personalized oncology and for engineering immunotherapy regimens.

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<![CDATA[Enhanced therapeutic index of an antimicrobial peptide in mice by increasing safety and activity against multidrug-resistant bacteria]]> https://www.researchpad.co/article/elastic_article_7718 The rising prevalence of antibiotic resistance underscores the urgent need for novel antimicrobial agents. Antimicrobial peptides (AMPs) are potentially effective therapeutics that disrupt bacterial membranes regardless of resistance to traditional antibiotics. We have developed engineered cationic AMPs (eCAPs) with broad activity against multidrug-resistant (MDR) bacteria, but stability remains an important concern. Therefore, we sought to enhance the clinical utility of eCAP WLBU2 in biological matrices relevant to respiratory infection. A designed substitution of d-Val for l-Val resulted in increased resistance to protease enzymatic degradation. We observed multiple gains of functions such as higher activity against bacteria in biofilm mode of growth, significantly lower toxicity to erythrocytes and white blood cells compared to WLBU2, with increased safety in mice. Direct airway delivery revealed a therapeutic index of >140 for the selected enantiomer compared to that of <35 for WLBU2. The data warrant clinical exploration by aerosolized delivery to mitigate MDR-related respiratory infection.

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<![CDATA[Bioenergetic-active materials enhance tissue regeneration by modulating cellular metabolic state]]> https://www.researchpad.co/article/Nf339299e-3ebd-42ea-b2c8-863f8ed912ab

We report a biodegradable synthetic material that opens a door to repair damaged tissue via boosting cellular energy metabolism.

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<![CDATA[Cell reprogramming using extracellular vesicles from differentiating stem cells into white/beige adipocytes]]> https://www.researchpad.co/article/N373547b3-4507-4b5b-9c71-8a2f68832b55

Extracellular vesicles derived during differentiation of stem cells have the potential to induce tissue-specific differentiation.

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<![CDATA[Phagocytosis of Wnt inhibitor SFRP4 by late wound macrophages drives chronic Wnt activity for fibrotic skin healing]]> https://www.researchpad.co/article/N4478c0b2-0fdd-4629-9ed1-5840fdce35e5

Macrophages, renowned for clearance of debris and bacteria in the wound, can also uptake signaling inhibitors to promote fibrosis.

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<![CDATA[Surface-anchored framework for generating RhD-epitope stealth red blood cells]]> https://www.researchpad.co/article/Nb921b2a9-1b2d-4275-b3b3-48bfa8c6beb0

A new method generates universal red blood cells for transfusion and requires no blood type match.

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<![CDATA[Biomimetic human small muscular pulmonary arteries]]> https://www.researchpad.co/article/N4f37bff7-25ac-41fc-ac72-b29adce218ab

Biofabricated mass-producible arteries containing layered and aligned cells and matrix exhibit enhanced cellular function.

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<![CDATA[Single-cell mass cytometry reveals cross-talk between inflammation-dampening and inflammation-amplifying cells in osteoarthritic cartilage]]> https://www.researchpad.co/article/N35d014c7-3802-4ddf-9c65-53315dda6549

This study defines a single-cell proteomic atlas of human OA cartilage to reveal rare subpopulations that stratify patients.

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<![CDATA[The mechanism of Hsp90-induced oligomerizaton of Tau]]> https://www.researchpad.co/article/Nb2439e1b-b5e6-4a00-ad26-1f7e5fff6d29

The chaperone Hsp90 remodels the structural ensemble of Tau, resulting in the formation of potentially neurotoxic oligomers.

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<![CDATA[Biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation for functional sweat gland regeneration]]> https://www.researchpad.co/article/N8515143b-6116-4ad6-818d-8ad9ce9c6055

3D-bioprinted microenvironment directs MSC differentiation and promotes SG regeneration.

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<![CDATA[Hydrogel cross-linking–programmed release of nitric oxide regulates source-dependent angiogenic behaviors of human mesenchymal stem cell]]> https://www.researchpad.co/article/N5300f023-74ca-4469-9b52-00818f5929b5

hMSC source-specific behaviors in 3D NO gel represent EC-like differentiation of ADSCs and pericyte-like characteristics of BMSCs.

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<![CDATA[Targeted anti–IL-1β platelet microparticles for cardiac detoxing and repair]]> https://www.researchpad.co/article/N20c23b3b-4bda-4f30-95dd-355840fea111

Platelet microparticles are used to deliver IL-1β antibodies to myocardial infarction for cardiac detoxing and repair.

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<![CDATA[Dense hydroxyl polyethylene glycol dendrimer targets activated glia in multiple CNS disorders]]> https://www.researchpad.co/article/N43f28b0d-e2d2-4799-9933-b582c6634bcd

PEGOL-60, a ligand-free high hydroxyl surface density dendrimer, targets neuroinflammation from systemic administration.

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<![CDATA[Focused ultrasound delivery of a selective TrkA agonist rescues cholinergic function in a mouse model of Alzheimer’s disease]]> https://www.researchpad.co/article/N8ad3bc51-1e7b-40d0-ba4f-56832e66d45b

Focused ultrasound delivery of a selective TrkA agonist rescues cholinergic function in a mouse model of Alzheimer’s disease.

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<![CDATA[Light-degradable hydrogels as dynamic triggers for gastrointestinal applications]]> https://www.researchpad.co/article/N32f565f2-9689-4710-9608-b145ae9a615e

Light-triggerable hydrogels enable on-demand degradation of gastrointestinal-resident devices, reducing the need for invasive interventions.

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<![CDATA[Poly(vinyl alcohol) boosting therapeutic potential of p-boronophenylalanine in neutron capture therapy by modulating metabolism]]> https://www.researchpad.co/article/N67e3d71d-105b-46dc-8ede-06d9c54b6b83

Extremely simple poly(vinyl alcohol) enhances therapeutic potential of p-boronophenylalanine by modulating its metabolism.

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<![CDATA[Biophysical and biomolecular interactions of malaria-infected erythrocytes in engineered human capillaries]]> https://www.researchpad.co/article/N59e18039-dccf-49a2-822f-cdd37f23fec2

Engineered human capillaries reveal distinct contributions of hemodynamics and cytoadhesion in malaria parasite sequestration.

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<![CDATA[Focusing light inside live tissue using reversibly switchable bacterial phytochrome as a genetically encoded photochromic guide star]]> https://www.researchpad.co/article/Na2964bdf-7853-4ff3-894d-8e36521be67a

A genetically encoded photochromic guide star is used for focusing light inside live tissue by wavefront shaping.

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<![CDATA[Identification of the hyaluronic acid pathway as a therapeutic target for facioscapulohumeral muscular dystrophy]]> https://www.researchpad.co/article/Nbf7306fd-06e9-44fd-a799-976c93212fea

Inhibition of HA synthesis blocks DUX4-induced pathologies.

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<![CDATA[Necrotizing enterocolitis is preceded by increased gut bacterial replication, Klebsiella, and fimbriae-encoding bacteria]]> https://www.researchpad.co/article/N818bc232-3b49-4a89-b793-cba8d0974642

Metagenomic analysis identifies microbial signatures preceding necrotizing enterocolitis development in premature infants.

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