Muscle contributions to propelling the body upward differ between skipping and running.

Skipping represents a training alternative to running due to its lower knee contact forces and higher whole-body metabolic cost. The increased metabolic cost of skipping is associated with a higher vertical center-of-mass (COM) displacement during the support and flight phases of the skipping hop compared to running. However, skipping has lower muscle force impulses than running.

Correlates of Cetuximab Efficacy in Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma Previously Treated With Immunotherapy.

Purpose: Immune checkpoint inhibitors (ICIs) are now first-line therapy for most patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), and cetuximab is most often used as subsequent therapy. However, data describing cetuximab efficacy in the post-ICI setting are limited.

Methods: We performed a single-institution retrospective analysis of patients with R/M HNSCC treated with cetuximab, either as monotherapy or in combination with chemotherapy, after receiving an ICI.

Integrative genomic analysis of DLBCL identifies immune environments associated with bispecific antibody response.

Most diffuse large B-cell lymphoma (DLBCL) patients treated with immunotherapies such as bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was applied to multiple large independent datasets in order to characterize DLBCL immune environments, and to define their association with tumor cell-intrinsic genomic alterations and outcomes to CD19-directed CAR T-cell and CD20 x CD3 BsAb therapies. This approach effectively segregated DLBCLs into four immune quadrants (IQ) defined by cell-of-origin and immune-related gene set expression scores.

Protection of β2GPI-Deficient Mice from Thrombosis Reflects a Defect in PAR3-facilitated Platelet Activation.

Antibodies to β2-glycoprotein I (β2GPI) cause thrombosis in antiphospholipid syndrome, however the role of β2GPI in coagulation in vivo is not understood. To address this issue, we developed β2GPI-deficient mice (Apoh-/-) by deleting exon 2 and 3 of Apoh using CRISPR/Cas9 and compared the development of thrombosis in wild-type (WT) and Apoh-/- mice using rose bengal and FeCl3-induced carotid thrombosis, laser-induced cremaster arteriolar injury, and inferior vena cava (IVC) stasis models. We also compared tail bleeding times and activation of platelets from WT and Apoh-/- mice in the absence and presence of β2GPI.

Highly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations.

Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.

Daytime DNase-I Administration Protects Mice From Ischemic Stroke Without Inducing Bleeding or tPA-Induced Hemorrhagic Transformation, Even With Aspirin Pretreatment.

Background: Acute ischemic stroke treatment typically involves tissue-type plasminogen activator (tPA) or tenecteplase, but about 50% of patients do not achieve successful reperfusion. The causes of tPA resistance, influenced by thrombus composition and timing, are not fully clear. Neutrophil extracellular traps (NETs), associated with poor outcomes and reperfusion resistance, contribute to thrombosis.

The primary mechanism for highly potent inhibition of HIV-1 maturation by lenacapavir.

Lenacapavir (LEN) is a highly potent, long-acting antiretroviral medication for treating people infected with muti-drug-resistant HIV-1 phenotypes. The inhibitor targets multifaceted functions of the viral capsid protein (CA) during HIV-1 replication. Previous studies have mainly focused on elucidating LEN's mode of action during viral ingress.

The effects of xylazine on locomotion and motor behaviour in a planarian model.

In recent years, the recreational use of xylazine has increased dramatically in the USA. Although xylazine has been used as an anesthetic in veterinary medicine for decades, little is known about its behavioral effects. We took advantage of the planarian's innate negative phototaxis, the reliable movement from the light side to the dark side of a Petri dish, to explore the organism's suitability as an animal model for investigating the preclinical pharmacology of xylazine.

Coordinated neuron-glia regeneration through Notch signaling in planarians.

Some animals can regenerate large missing regions of their nervous system, requiring mechanisms to restore the pattern, numbers, and wiring of diverse neuron classes. Because injuries are unpredictable, regeneration must be accomplished from an unlimited number of starting points. Coordinated regeneration of neuron-glia architecture is thus a major challenge and remains poorly understood.

Comprehensive guide for epigenetics and transcriptomics data quality control.

Host response to environmental exposures such as pathogens and chemicals can include modifications to the epigenome and transcriptome. Improved signature discovery, including the identification of the agent and timing of exposure, has been enabled by advancements in assaying techniques to detect RNA expression, DNA base modifications, histone modifications, and chromatin accessibility. The interrogation of the epigenome and transcriptome cascade requires analyzing disparate datasets from multiple assay types, often at single-cell resolution, derived from the same biospecimen.

White matter connections within the central sulcus subserving the somato-cognitive action network.

The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield's motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the 'plis de passage' of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network.

Developing predictive nomogram models using quantitative electroencephalography for brain function in type a aortic dissection: a prospective observational study.

Background: Type A aortic dissection (TAAD) remains a significant challenge in cardiac surgery, presenting high risks of adverse outcomes such as permanent neurological dysfunction and mortality despite advances in medical technology and surgical techniques. This study investigates the use of quantitative electroencephalography (QEEG) to monitor and predict neurological outcomes during the perioperative period in TAAD patients.

Methods: This prospective observational study was conducted at the hospital, involving patients undergoing TAAD surgery from February 2022 to January 2023.

Multifunctional DNA-Collagen Biomaterials: Developmental Advances and Biomedical Applications.

The complexation of nucleic acids and collagen forms a platform biomaterial greater than the sum of its parts. This union of biomacromolecules merges the extracellular matrix functionality of collagen with the designable bioactivity of nucleic acids, enabling advances in regenerative medicine, tissue engineering, gene delivery, and targeted therapy. This review traces the historical foundations and critical applications of DNA-collagen complexes and highlights their capabilities, demonstrating them as biocompatible, bioactive, and tunable platform materials.

Impact of Race/Ethnicity on Clinical and Genomic Characteristics, Trial Participation, and Genotype-Matched Therapy among Patients with Metastatic Breast Cancer.

Background: Race/ethnicity may affect outcomes in metastatic breast cancer (MBC) due to biological and social determinants. We evaluated the impact of race/ethnicity on clinical, socioeconomic, and genomic characteristics, clinical trial participation, and receipt of genotype-matched therapy among patients with MBC.

Methods: A retrospective study of patients with MBC who underwent cell-free DNA testing (cfDNA, Guardant360â, 74 gene panel) between 11/2016 and 11/2020 was conducted.

EValuating Glucose ContrOL Using a Next-GeneraTION Automated Insulin Delivery Algorithm in Patients with Type 1 and Type 2 Diabetes: The EVOLUTION Study.

This study evaluated a next-generation automated insulin delivery (AID) algorithm for Omnipod in type 1 and type 2 diabetes across multiple phases: 14-day run-in with usual therapy, 48-h AID use in a hotel setting (type 1 only), and up to 6 weeks of outpatient AID use. Participants did, or did not, deliver manual boluses at alternating periods. Twelve adults with type 1 diabetes completed the hotel phase; 9 of those 12 plus 8 adults with type 2 diabetes completed the subsequent outpatient phase.

Long Term Outcomes of Transplant Recipients Comparing Belatacept vs. Tacrolimus: A UNOS Database Analysis.

Calcineurin inhibitors have been the choice for maintenance immunosuppression (IS) in kidney transplant recipients (KTR), but they are associated with nephrotoxicity and metabolic side effects. We aim to compare the long-term outcomes of KTR on belatacept (bela) versus tacrolimus (tac) IS, in all KTRs and various subgroups. Using the UNOS-STAR files, we identified adult first-KTR from 2010 to 2022.

Case Report: ESR1::CITED2 Fusion in a Malignant Uterine Tumor Resembling Ovarian Sex Cord Tumor.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare, typically benign uterine tumor occurring over a wide age range (mean 52.4 yr). UTROSCTs often harbor translocations between ESR1 and nuclear receptor coactivators NCOA1-NCOA3.

Validation of Tumor Budding as a Prognostic Factor in Ovarian Clear Cell Carcinoma Using an Independent Cohort.

Ovarian clear cell carcinoma (OCCC) is an endometriosis-related neoplasm, in which traditional histologic grading does not show prognostic significance. Tumor budding was associated with poorer outcomes in OCCC in previous studies. We aimed to evaluate the prognostic significance of tumor budding in OCCC in an independent cohort.