Inflammation switches the chemoattractant requirements for naive lymphocyte entry into lymph nodes.

Sustained lymphocyte migration from blood into lymph nodes (LNs) is important for immune responses. The CC-chemokine receptor-7 (CCR7) ligand CCL21 is required for LN entry but is downregulated during inflammation, and it has been unclear how recruitment is maintained. Here, we show that the oxysterol biosynthetic enzyme cholesterol-25-hydroxylase (Ch25h) is upregulated in LN high endothelial venules during viral infection.

Hardware Complication Risks in Head and Neck Cancer Patients Undergoing Reconstructive Surgery With Segmental Mandibulectomy.

Background: The primary objective of this study was to ascertain the risk factors associated with hardware complications following segmental mandibular reconstruction in head and neck cancer patients. Additionally, we sought to develop a nomogram model that enables accurate risk prediction.

Methods: Patients who underwent segmental mandibulectomy with immediate free or local regional tissue transfer between January 2016 and December 2020 were reviewed.

A home-based self-directed EEG neurofeedback intervention for people with chronic neuropathic pain following spinal cord injury (the StoPain Trial): description of the intervention.

Study Design: Randomised controlled trial.

Objectives: The objective is to describe an electroencephalography (EEG) neurofeedback intervention that will be provided in a randomised controlled trial for people with neuropathic pain following spinal cord injury (SCI): the StoPain Trial. In this trial, participants in the treatment group will implement an EEG neurofeedback system as an analgesic intervention at home, while participants in the control group will continue with the treatments available to them in the community.

Early Complications of Planned Resection Versus Unplanned Excision of Sarcomas in the Distal Upper Extremity.

Purpose: Unplanned excisions are defined as excisions of malignant tumors performed without preoperative cross-sectional imaging or diagnostic biopsy, frequently resulting in residual disease and re-excision secondary to positive surgical margins. The purpose of this study was to compare the relative morbidity of planned versus unplanned upper-extremity sarcoma excisions.

Methods: A single tertiary referral hospital pathology database was queried from January 2015 through 2022 for primary upper-extremity sarcomas (forearm, wrist, hand, and finger).

Artificial intelligence-assisted grading for tear trough deformity.

Background: Various classification systems for tear trough deformity (TTD) have been published; however, their complexity can pose challenges in clinical use, especially for less experienced surgeons. It is believed that artificial intelligence (AI) technology can address some of these challenges by reducing inadvertent errors and improving the accuracy of medical practice. In this study, we aimed to establish a reliable and precise digital image grading model for TTD using smartphone-based photography enhanced using AI deep learning technology.

Larger Tumor Size and Elevated Serum Chromogranin A Levels Predict Metastatic Disease on DOTATATE Imaging in Patients with Gastroenteropancreatic Neuroendocrine Tumors.

Purpose: DOTATATE PET/CT (DOTATATE) is superior to conventional imaging in detecting metastasis for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, limited availability, high-cost, and additive radiation exposure necessitate guidelines for its use. This study seeks to investigate the relationship between clinical characteristics and metastasis on DOTATATE.

Mast cells help organize the Peyer's patch niche for induction of IgA responses.

Peyer's patches (PPs) are lymphoid structures situated adjacent to the intestinal epithelium that support B cell responses that give rise to many intestinal IgA-secreting cells. Induction of isotype switching to IgA in PPs requires interactions between B cells and TGFβ-activating conventional dendritic cells type 2 (cDC2s) in the subepithelial dome (SED). However, the mechanisms promoting cDC2 positioning in the SED are unclear.

Outcomes of Distal Radius Fractures in Solid Organ Transplant Recipients.

Purpose: Distal radius fractures (DRFs) are one of the most common conditions that musculoskeletal providers treat. As the frequency of solid organ transplants (SOT) increases, these providers are often called upon to manage DRFs in these patients. These patients are at increased risk for osteopenia and osteoporosis, given the altered bone metabolism after SOT and frequent use of glucocorticoid and immunosuppressive medications.

Closing-wedge Osteotomies: Can We Do and Teach Better?

Background: Wedge osteotomies are ubiquitous in pediatric orthopaedics and limb deformity surgery; however, there is no universally preferred methodology for these procedures. This study aims to determine the relative accuracy and effectiveness of several measuring and marking methods to guide best practices for wedge-shaped osteotomies in long bones.

Methods: An observational cohort study was completed.

Modifiable and non-modifiable risk factors for failure of non-operative treatment of pediatric forearm fractures: Where can we do better?

Introduction: Distal third forearm fractures are common fractures in children. While outcomes are generally excellent, some patients fail initial non-operative management and require intervention. The purpose of this study is to identify independent risk factors associated with failure of closed reduction.

Platelets and mast cells promote pathogenic eosinophil recruitment during invasive fungal infection via the 5-HIAA-GPR35 ligand-receptor system.

Cryptococcus neoformans is the leading cause of fungal meningitis and is characterized by pathogenic eosinophil accumulation in the context of type-2 inflammation. The chemoattractant receptor GPR35 is expressed by granulocytes and promotes their migration to the inflammatory mediator 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite. Given the inflammatory nature of cryptococcal infection, we examined the role of GPR35 in the circuitry underlying cell recruitment to the lung.

Oncogenic mutations impede nuclear RNA surveillance.

RNA surveillance pathways detect and degrade defective transcripts to ensure RNA fidelity. We found that disrupted nuclear RNA surveillance is oncogenic. Cyclin-dependent kinase 13 () is mutated in melanoma, and patient-mutated accelerates zebrafish melanoma.

Antigen discrimination by T cells relies on size-constrained microvillar contact.

T cells use finger-like protrusions called 'microvilli' to interrogate their targets, but why they do so is unknown. To form contacts, T cells must overcome the highly charged, barrier-like layer of large molecules forming a target cell's glycocalyx. Here, T cells are observed to use microvilli to breach a model glycocalyx barrier, forming numerous small (<0.

Impact of Baseline Clinical Biomarkers on Treatment Outcomes in Patients With Advanced NSCLC Receiving First-line Pembrolizumab-Based Therapy.

Background: While the introduction of immune checkpoint inhibitors (ICI) such as pembrolizumab has significantly improved survival for patients with metastatic non-small cell lung cancer (NSCLC), there remains a need for improved predictive and prognostic biomarkers.

Patients And Methods: We conducted a retrospective, 3-center study using electronic medical record data for patients with stage IV NSCLC treated with first-line pembrolizumab, either as monotherapy or in combination with chemotherapy, between 2014 and 2019. We categorized variables as covariates or confounders.

Plerixafor strategies for autologous hematopoietic cell transplant mobilization: A comparison of efficacy and cost.

Addition of plerixafor (P) to granulocyte colony stimulating factor (G-CSF) during peripheral blood mobilization of hematopoietic stem cells (HSC) increases the number of patients meeting collection goals prior to autologous stem cell transplant (aSCT). However, use of P is not universal among transplant centers due to cost. This study aims to compare clinical and financial impacts of using an algorithm-based P mobilization strategy versus use in all patients.

Trapping or slowing the diffusion of T cell receptors at close contacts initiates T cell signaling.

T cell activation is initiated by T cell receptor (TCR) phosphorylation. This requires the local depletion of large receptor-type phosphatases from "close contacts" formed when T cells interact with surfaces presenting agonistic TCR ligands, but exactly how the ligands potentiate signaling is unclear. It has been proposed that TCR ligands could enhance receptor phosphorylation and signaling just by holding TCRs in phosphatase-depleted close contacts, but this has not been directly tested.

High-resolution characterization of gene function using single-cell CRISPR tiling screen.

Identification of novel functional domains and characterization of detailed regulatory mechanisms in cancer-driving genes is critical for advanced cancer therapy. To date, CRISPR gene editing has primarily been applied to defining the role of individual genes. Recently, high-density mutagenesis via CRISPR tiling of gene-coding exons has been demonstrated to identify functional regions in genes.

Soft Polydimethylsiloxane-Supported Lipid Bilayers for Studying T Cell Interactions.

Much of what we know about the early stages of T cell activation has been obtained from studies of T cells interacting with glass-supported lipid bilayers that favor imaging but are orders of magnitude stiffer than typical cells. We developed a method for attaching lipid bilayers to polydimethylsiloxane polymer supports, producing "soft bilayers" with physiological levels of mechanical resistance (Young's modulus of 4 kPa). Comparisons of T cell behavior on soft and glass-supported bilayers revealed that whereas late stages of T cell activation are thought to be substrate-stiffness dependent, early calcium signaling was unaffected by substrate rigidity, implying that early steps in T cell receptor triggering are not mechanosensitive.

Testing of a Program to Automatically Analyze Students' Concept Maps.

Concept maps are graphical representations of how various concepts relate to one another. Assessment of concept maps developed by students in the pharmacy curriculum helps to evaluate student understanding of course material. However, providing feedback on concept maps can be time-consuming and often requires the grader to be a content expert.

Palmitate-Induced IRE1-XBP1-ZEB Signaling Represses Desmoplakin Expression and Promotes Cancer Cell Migration.

Elevated uptake of saturated fatty acid palmitate is associated with metastatic progression of cancer cells; however, the precise signaling mechanism behind the phenomenon is unclear. The loss of cell adhesion proteins, such as desmoplakin (DSP), is a key driving event in the transformation of cancer cells to more aggressive phenotypes. Here, we investigated the mechanism by which palmitate induces the loss of DSP in liver and breast cancer cells.

Fabrication of Zero Mode Waveguides for High Concentration Single Molecule Microscopy.

In single molecule fluorescence enzymology, background fluorescence from labeled substrates in solution often limits fluorophore concentration to pico- to nanomolar ranges, several orders of magnitude less than many physiological ligand concentrations. Optical nanostructures called zero mode waveguides (ZMWs), which are 100-200 nm in diameter apertures fabricated in a thin conducting metal such as aluminum or gold, allow imaging of individual molecules at micromolar concentrations of fluorophores by confining visible light excitation to zeptoliter effective volumes. However, the need for expensive and specialized nanofabrication equipment has precluded the widespread use of ZMWs.