Importance: Randomized clinical trials have shown the safety and efficacy of faricimab as a novel vascular endothelial growth factor and angiopoietin-2 inhibitor in the treatment of neovascular age-related macular degeneration (nAMD) and macular edema of various etiologies. However, more rare adverse events may not be considered in clinical trials.
Objective: To describe 3 eyes that developed irreversible vision loss following initial mild intraocular inflammation (IOI) to faricimab.
Background: Fruits and vegetables are primary sources of vitamins and minerals that may alleviate the risk of chronic illnesses. However, Indian adolescents consume inadequate amounts of fruits and vegetables, with less than 10% meeting recommendations. Micronutrient deficiencies are a major public health problem in India.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
TGFβ family ligands are synthesized as precursors consisting of an N-terminal prodomain and C-terminal growth factor (GF) signaling domain. After proteolytic processing, the prodomain typically remains noncovalently associated with the GF, sometimes forming a high-affinity latent procomplex that requires activation. For the TGFβ family ligand anti-Müllerian hormone (AMH), the prodomain maintains a high-affinity interaction with its GF that does not render it latent.
View Article and Find Full Text PDFBackground: Head and neck squamous cell carcinoma (HNSCC) presents significant treatment challenges, particularly in cases unrelated to human papillomavirus (HPV). The chemokine receptor CXCR4, interacting with its ligand CXCL12, plays a crucial role in tumor proliferation, metastasis, and treatment resistance. This study explores the therapeutic potential of engineered monomeric and dimerized CXCL12 variants (CXCL12 and CXCL12, respectively) in HNSCC and evaluates potential additive effects when combined with radiation therapy.
View Article and Find Full Text PDFSodium dodecyl sulfate (SDS) plays a pivotal role in protein denaturation, tissue extraction, and protein mass-based electrophoretic separations. However, even modest concentrations of SDS can cause column overpressure, retention time shifts, and ionization signal suppression during liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses. Thus, SDS removal is a critical step for LC-MS/MS analysis of protein digests containing SDS.
View Article and Find Full Text PDFBackground: Up to half of all surgical adverse events are due to non-technical errors, making non-technical skill assessment and improvement a priority. No specific tools are available to retrospectively identify non-technical errors that have occurred in surgical patient care. This original study aimed to develop and provide evidence of validity and inter-rater reliability for the System for Identification and Categorization of Non-technical Error in Surgical Settings (SICNESS).
View Article and Find Full Text PDFWeakly-coordinating anions (WCAs) are employed in a wide range of applications, but limitations remain, including high reactivity, limited redox window, complicated synthesis, high cost, low solublity, and low structural tunabililty. Herein, we report a new class of WCA based on alkyl or aryl (R) substituted silicates bearing fluorinated pinacolate ligands, "[Si ]". Anions bearing a variety of R groups were prepared, enabling facile tuning of sterics and solubility.
View Article and Find Full Text PDFThe human gut microbiome (GM) undergoes dynamic changes throughout life, transitioning from infancy to adulthood. Despite improved understanding over the past years about how genetics, lifestyle, and the external environment impact the GM, limited research has explored the GM's evolution during late-stage adolescence, especially among college students. This study addresses this gap by investigating the longitudinal dynamics of fecal microbial, functional, and metabolomic signatures in a diverse group of first-year, dormitory-housed college students.
View Article and Find Full Text PDFMany virus genomes encode proteases that facilitate infection. The molecular mechanism of plant recognition of viral proteases is largely unexplored. Using the system of and cowpea mosaic virus (CPMV), we identified a cowpea lipid transfer protein (LTP1) which interacts with CPMV-encoded 24KPro, a cysteine protease, but not with the enzymatically inactive mutant 24KPro(C166A).
View Article and Find Full Text PDFObjective: To identify the effects of chronic pain levels on static and dynamic postural (DP) control in individuals with chronic ankle instability (CAI).
Design: Cross-sectional study.
Setting: Controlled laboratory.
Skeletal muscle contraction evokes numerous biochemical alterations that underpin exercise benefits. This present study aimed to elucidate the mechanism for electrical pulse stimulation (EPS)-induced antioxidant adaptation in C2C12 myotubes. We found that EPS significantly upregulated Nrf2 and a broad array of downstream antioxidant enzymes involved in multiple antioxidant systems.
View Article and Find Full Text PDFDespite the promise of concurrent radiotherapy (RT) and immunotherapy in head and neck cancer (HNC), multiple randomized trials of this combination have had disappointing results. To evaluate potential immunologic mechanisms of RT resistance, we compared pre-treatment HNCs that developed RT resistance to a matched cohort that achieved curative status. Gene set enrichment analysis demonstrated that a pre-treatment pro-immunogenic tumor microenvironment (TME), including type II interferon [interferon gamma (IFNγ)] and tumor necrosis factor alpha (TNFα) signaling, predicted cure while type I interferon [interferon alpha (IFNα)] enrichment was associated with an immunosuppressive TME found in tumors that went on to recur.
View Article and Find Full Text PDFBackground: Although individuals with anterior cruciate ligament reconstruction (ACLR) are at high risk for posttraumatic osteoarthritis, mechanisms underlying the relationship between running and knee cartilage health remain unclear.
Objective: We aimed to investigate how 30 min of running influences femoral cartilage thickness and composition and their relationships with running biomechanics in patients with ACLR and controls.
Methods: Twenty patients with ACLR (time post-ACLR: 14.
On any given day, we make countless reaching movements to objects around us. While such ubiquity may suggest uniformity, each movement's speed is unique-why is this? Reach speed is known to be influenced by accuracy; we slow down to sustain high accuracy. However, in other forms of movement like walking or running, metabolic cost is often the primary determinant of movement speed.
View Article and Find Full Text PDFWe developed a simple, paper-based device that enables sensitive detection by mass spectrometry (MS) without solid phase extraction or other sample preparation. Using glass fiber filter papers within a 3D printed holder, the device employs electrokinetic manipulations to stack, separate, and desalt charged molecules on paper prior to spray into the MS. Due to counter-balanced electroosmotic flow and electrophoresis, charged analytes stack on the paper and desalting occurs in minutes.
View Article and Find Full Text PDFMost TGFβ family ligands exist as procomplexes consisting of a prodomain noncovalently bound to a growth factor (GF); Whereas some prodomains confer latency, the Anti-Müllerian Hormone (AMH) prodomain maintains a remarkably high affinity for the GF yet remains active. Using single particle EM methods, we show the AMH prodomain consists of two subdomains: a vestigial TGFβ prodomain-like fold and a novel, helical bundle GF-binding domain, the result of an exon insertion 450 million years ago, that engages both receptor epitopes. When associated with the prodomain, the AMH GF is distorted into a strained, open conformation whose closure upon bivalent binding of AMHR2 displaces the prodomain through a conformational shift mechanism to allow for signaling.
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