Factors Contributing to Follow-up Nonadherence After Infectious Keratitis Diagnosis.

Objectives: To evaluate demographic, socioeconomic, and clinical factors associated with nonadherence with initial follow-up after a diagnosis of infectious keratitis.

Methods: A retrospective chart review of patients aged 18 to 60 years who were diagnosed with infectious keratitis at the Wills Eye Hospital Emergency Room from March 2019 to September 2019 was conducted. The primary outcome was nonadherence with initial follow-up recommendation and included patients who did not follow-up in the time frame requested by the diagnosing physician and those who were lost to follow-up.

Performance of an AI-powered visualization software platform for precision surgery in breast cancer patients.

Surgery remains the primary treatment modality in the management of early-stage invasive breast cancer. Artificial intelligence (AI)-powered visualization platforms offer the compelling potential to aid surgeons in evaluating the tumor's location and morphology within the breast and accordingly optimize their surgical approach. We sought to validate an AI platform that employs dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to render three-dimensional (3D) representations of the tumor and 5 additional chest tissues, offering clear visualizations as well as functionalities for quantifying tumor morphology, tumor-to-landmark structure distances, excision volumes, and approximate surgical margins.

Timing Matters: Late, but Not Early, Exercise Training Ameliorates MASLD in Part by Modulating the Gut-Liver Axis in Mice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development.

Itaconate transporter SLC13A3 impairs tumor immunity via endowing ferroptosis resistance.

Immune checkpoint blockade (ICB) triggers tumor ferroptosis. However, most patients are unresponsive to ICB. Tumors might evade ferroptosis in the tumor microenvironment (TME).

Autoinhibition of dimeric NINJ1 prevents plasma membrane rupture.

Lytic cell death culminates in plasma membrane rupture, which releases large intracellular molecules to augment the inflammatory response. Plasma membrane rupture is mediated by the effector membrane protein ninjurin-1 (NINJ1), which polymerizes and ruptures the membrane via its hydrophilic face. How NINJ1 is restrained under steady-state conditions to ensure cell survival remains unknown.

Exogenous strigolactones alleviate low-temperature stress in peppers seedlings by reducing the degree of photoinhibition.

Background: The growth and yield of pepper, a typical temperature-loving vegetable, are limited by low-temperature environments. Using low-temperature sensitive 'Hangjiao No. 4' (Capsicum annuum L.

Vinegar - a beneficial food additive: production, safety, possibilities, and applications from ancient to modern times.

Vinegar is a natural product derived from fruits or grains after being subjected to food fermentation processes. Vinegar is a beneficial food additive, preservative, and condiment. It is appreciated across the Islamic world following the Prophetic teaching where Prophet Muhammad (peace be upon him) recommended its utility, saying: "The best of condiments is vinegar".

Population pharmacokinetic-pharmacodynamic model of elinzanetant based on integrated clinical phase I and II data.

Elinzanetant is a potent and selective dual neurokin-1 (NK-1) and -3 (NK-3) receptor antagonist that is currently developed for the treatment of women with moderate-to-severe vasomotor symptoms (VMS) associated with menopause. Here, we report the development of a population pharmacokinetic (popPK) model for elinzanetant and its principal metabolites based on an integrated dataset from 366 subjects (including 197 women with VMS) collected in 10 phase I or II studies. The pharmacokinetics of elinzanetant and its metabolites could be well described by the popPK model.

Agonist antibody to guanylate cyclase receptor NPR1 regulates vascular tone.

Heart failure is a leading cause of morbidity and mortality. Elevated intracardiac pressures and myocyte stretch in heart failure trigger the release of counter-regulatory natriuretic peptides, which act through their receptor (NPR1) to affect vasodilation, diuresis and natriuresis, lowering venous pressures and relieving venous congestion. Recombinant natriuretic peptide infusions were developed to treat heart failure but have been limited by a short duration of effect.

Comparison of Biological Augmentation in Rotator Cuff Repair Using Inflamed Versus Noninflamed Bursal Tissue in Rats.

Purpose: To examine how augmentation of a rotator cuff repair with inflamed versus noninflamed bursal tissue affects tendon-to-bone healing in a rat model of rotator cuff repair.

Methods: A total of 136 Sprague-Dawley rats were randomly assigned to an inflamed or noninflamed bursal tissue application group. After detachment, the supraspinatus tendon was reattached with bursal tissue sewn onto the tendon-to-bone interface.

Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.

While significant advances have been made in understanding renal pathophysiology, less is known about the role of glycosphingolipid (GSL) metabolism in driving organ dysfunction. Here, we used a small molecule inhibitor of glucosylceramide synthase to modulate GSL levels in three mouse models of distinct renal pathologies: Alport syndrome (Col4a3 KO), polycystic kidney disease (Nek8), and steroid-resistant nephrotic syndrome (Nphs2 cKO). At the tissue level, we identified a core immune-enriched transcriptional signature that was shared across models and enriched in human polycystic kidney disease.

LILRB4 on multiple myeloma cells promotes bone lesion by p-SHP2/NF-κB/RELT signal pathway.

Background: Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion.

Antibody-activation of connexin hemichannels in bone osteocytes with ATP release suppresses breast cancer and osteosarcoma malignancy.

Bone tissue represents the most frequent site of cancer metastasis. We developed a hemichannel-activating antibody, Cx43-M2. Cx43-M2, directly targeting osteocytes in situ, activates osteocytic hemichannels and elevates extracellular ATP, thereby inhibiting the growth and migration of cultured breast and osteosarcoma cancer cells.

Additive manufacturing of an ultrastrong, deformable Al alloy with nanoscale intermetallics.

Light-weight, high-strength, aluminum (Al) alloys have widespread industrial applications. However, most commercially available high-strength Al alloys, like AA 7075, are not suitable for additive manufacturing due to their high susceptibility to solidification cracking. In this work, a custom Al alloy AlTiFeCoNi is fabricated by selective laser melting.

Blocking Oncostatin M receptor abrogates STAT3 mediated integrin signaling and overcomes chemoresistance in ovarian cancer.

Chemotherapy such as cisplatin is widely used to treat ovarian cancer either before or after surgical debulking. However, cancer relapse due to chemotherapy resistance is a major challenge in the treatment of ovarian cancer. The underlying mechanisms related to chemotherapy resistance remain largely unclear.

Decoding 2.3 million ECGs: interpretable deep learning for advancing cardiovascular diagnosis and mortality risk stratification.

Aims: Electrocardiogram (ECG) is widely considered the primary test for evaluating cardiovascular diseases. However, the use of artificial intelligence (AI) to advance these medical practices and learn new clinical insights from ECGs remains largely unexplored. We hypothesize that AI models with a specific design can provide fine-grained interpretation of ECGs to advance cardiovascular diagnosis, stratify mortality risks, and identify new clinically useful information.

Discovery of potent small-molecule inhibitors of lipoprotein(a) formation.

Lipoprotein(a) (Lp(a)), an independent, causal cardiovascular risk factor, is a lipoprotein particle that is formed by the interaction of a low-density lipoprotein (LDL) particle and apolipoprotein(a) (apo(a)). Apo(a) first binds to lysine residues of apolipoprotein B-100 (apoB-100) on LDL through the Kringle IV (K) 7 and 8 domains, before a disulfide bond forms between apo(a) and apoB-100 to create Lp(a) (refs. ).

Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1.

Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV-1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion-stabilized HIV-1 envelope (Env) trimer, BG505 DS-SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4-binding site (CD4bs) of vulnerability. Two of the vaccine-elicited CD4bs-targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a-hinge region and human IgG1-constant region (G36×3-IgG2a and R27×3-IgG2a), neutralized 96% of a multiclade 208-strain panel at geometric mean ICs of 0.

US-guided Percutaneous Radiofrequency Ablation for Secondary Hyperparathyroidism: Long-term Outcomes and Prognostic Factors.

Background Although favorable outcomes have been reported with radiofrequency ablation (RFA) for secondary hyperparathyroidism (SHPT), the long-term efficacy remains insufficiently investigated. Purpose To evaluate the long-term efficacy and safety of US-guided percutaneous RFA in patients with SHPT undergoing dialysis and to identify possible predictors associated with treatment failure. Materials and Methods This retrospective study included consecutive patients with SHPT with at least one enlarged parathyroid gland accessible for RFA who were undergoing dialysis at seven tertiary centers from May 2013 to July 2022.

A therapeutic hepatitis B mRNA vaccine with strong immunogenicity and persistent virological suppression.

Here we report on the development and comprehensive evaluations of an mRNA vaccine for chronic hepatitis B (CHB) treatment. In two different HBV carrier mouse models generated by viral vector-mediated HBV transfection (pAAV-HBV1.2 and rAAV8-HBV1.

Fc gamma receptors promote antibody-induced LILRB4 internalization and immune regulation of monocytic AML.

The immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4) is found specifically on the cell surface of acute monocytic leukemia (monocytic AML), an aggressive and common subtype of AML. We have developed a humanized monoclonal IgG LILRB4-blocking antibody (h128-3), which improved immune regulation but reduced cell surface expression of LILRB4 in monocytic AML models by 40-60%. Interestingly, most of this effect was neutralized by mutation of the Fc region of the antibody (h128-3/N297A), which prevents interaction with Fc gamma receptors (FcγRs).

2,6-diaminopurine (Z)-containing toehold probes improve genotyping sensitivity.

2,6-diaminopurine (Z), a naturally occurring noncanonical nucleotide base found in bacteriophages, enhances DNA hybridization by forming three hydrogen bonds with thymine (T). These distinct biochemical characteristics make it particularly valuable in applications that rely on the thermodynamics of DNA hybridization. However, the practical use of Z-containing oligos is limited by their high production cost and the challenges associated with their synthesis.