CXCL12 ameliorates neutrophilia and disease severity in SARS-CoV-2 infection.

Neutrophils, particularly low-density neutrophils (LDNs), are believed to contribute to acute COVID-19 severity. Here, we showed that neutrophilia can be detected acutely and even months after SARS-CoV-2 infection in patients and mice, while neutrophil depletion reduced disease severity in mice. A key factor in neutrophilia and severe disease in infected mice was traced to the chemokine CXCL12 secreted by bone marrow cells and unexpectedly, endothelial cells.

Acute infectious mononucleosis generates persistent, functional EBNA-1 antibodies with high cross-reactivity to alpha crystalline beta.

Epstein-Barr Virus (EBV) infects over 95% of the world's population and is the most common cause of infectious mononucleosis (IM). Epidemiologic studies have linked EBV with certain cancers or autoimmune conditions, including multiple sclerosis (MS). Recent studies suggest that molecular mimicry between EBV proteins, particularly EBV nuclear antigen 1 (EBNA-1), and self-proteins is a plausible mechanism through which EBV infection may contribute to the development of autoimmune disorders.

Geriatric Nutritional Risk Index and Postoperative Outcomes Following Head and Neck Cancer Surgery.

Background: The geriatric nutritional risk index (GNRI) is a tool to assess preoperative nutritional status that can be calculated simply based on height, weight, and serum albumin. This study assesses the utility of GNRI in predicting postoperative complications in patients undergoing major head and neck cancer (HNC) surgery.

Methods: Retrospective review of the 2016-2020 National Surgical Quality Improvement Program database.

SON-1010: an albumin-binding IL-12 fusion protein that improves cytokine half-life, targets tumors, and enhances therapeutic efficacy.

Background: Cytokines have been promising cancer immunotherapeutics for decades, yet only two are licensed to date. Interleukin-12 (IL-12) is a potent regulator of cell-mediated immunity that activates NK cells and interferon-γ (IFNγ) production. It plays a central role in multiple pathways that can enhance cancer cell death and modify the tumor microenvironment (TME).

A scalable framework for learning the geometry-dependent solution operators of partial differential equations.

Solving partial differential equations (PDEs) using numerical methods is a ubiquitous task in engineering and medicine. However, the computational costs can be prohibitively high when many-query evaluations of PDE solutions on multiple geometries are needed. Here we aim to address this challenge by introducing Diffeomorphic Mapping Operator Learning (DIMON), a generic artificial intelligence framework that learns geometry-dependent solution operators of different types of PDE on a variety of geometries.

Association of oropharyngeal cancer recurrence with tumor-intrinsic and immune-mediated sequelae of reduced genomic instability.

Background: Limited understanding of the biology predisposing certain human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) to relapse impedes therapeutic personalization. We aimed to identify molecular traits that distinguish recurrence-prone tumors.

Methods: 50 HPV+ OPSCCs that later recurred (cases) and 50 non-recurrent controls matched for stage, therapy, and smoking history were RNA-sequenced.

Free Flap Reconstruction of the Oropharynx.

Reconstruction of the oropharynx plays a critical role in preserving quality of life after surgical resection of oropharyngeal carcinoma. Free tissue is one of several reconstructive options, which can closely approximate native oropharyngeal anatomy and lead to favorable functional outcomes in carefully selected patients. Here, the authors provide an overview of the indications, treatment options, functional outcomes, potential complications, and future considerations for free flap reconstruction of the oropharynx.

Thyroid Malignancies With Thymic Differentiation: Outcomes of Rare SETTLE and CASTLE Tumors.

Background: Spindle epithelial tumors with thymus-like differentiation (SETTLE) and carcinomas showing thymus-like differentiation (CASTLE) are rare intrathyroid tumors.

Methods: This retrospective cohort study included patients diagnosed with SETTLE, CASTLE, and papillary thyroid carcinoma (PTC) from 2004 to 2020 within the National Cancer Database (NCDB). Demographic, tumor, and treatment characteristics were compared.

Ovarian cancer-derived IL-4 promotes immunotherapy resistance.

Ovarian cancer is resistant to immunotherapy, and this is influenced by the immunosuppressed tumor microenvironment (TME) dominated by macrophages. Resistance is also affected by intratumoral heterogeneity, whose development is poorly understood. To identify regulators of ovarian cancer immunity, we employed a spatial functional genomics screen (Perturb-map), focused on receptor/ligands hypothesized to be involved in tumor-macrophage communication.

Missed Adjuvant Therapy in Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma.

Objective: Investigate missed adjuvant therapy and associated disparities in overall survival (OS) for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC).

Methods: The 2010-2017 National Cancer Database was queried for patients with surgically resected HPV+ OPSCC. Indications for adjuvant radiotherapy (aRT) included pT3-4 classification, pN2-3 classification, lymphovascular invasion, pathologic extranodal extension (pENE), and/or positive surgical margins (PSM).

Choice of Adjuvant Radiotherapy Facility in Sinonasal Squamous Cell Carcinoma.

Objective: Undergoing surgery and adjuvant radiotherapy (aRT) at the same facility has been associated with higher overall survival (OS) in head and neck squamous cell carcinoma. Our study investigates whether undergoing surgery and aRT at the same academic facility is associated with higher OS compared with separate facilities in sinonasal squamous cell carcinoma (SNSCC).

Methods: The 2006 to 2017 National Cancer Database was queried for patients with SNSCC undergoing surgery at an academic facility followed by aRT with or without adjuvant chemotherapy.

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guerin (BCG) is the primary treatment for non-muscle-invasive bladder cancer (NMIBC), known to stimulate inflammatory cytokines, notably interferon (IFN)-γ. We observed that prolonged IFN-γ exposure fosters adaptive resistance in recurrent tumors, aiding immune evasion and tumor proliferation. We identify HLA-E and NKG2A, part of a novel NK and T cell checkpoint pathway, as key mediators of resistance in BCG-unresponsive NMIBC.

Primary site surgical resection in cM1 oral cavity squamous cell carcinoma.

Objective: To investigate primary site surgical resection and overall survival (OS) in clinically distantly metastatic (cM1) oral cavity squamous cell carcinoma (OCSCC).

Methods: The 2006-2018 National Cancer Database was queried for patients presenting with cM1 OCSCC who underwent chemotherapy. Binary logistic, Kaplan-Meier, and multivariable Cox proportional hazards regression models were implemented.

Impact of Facility Volume on Overall Survival in Patients With Head and Neck Cancer Undergoing Palliative Treatment.

Background: Treatment at high-volume facilities (HVF) has been associated with improved prognosis of HNC patients undergoing curative treatment. Whether this systemic factor influences survival outcomes of patients with HNC undergoing palliative treatment is unknown.

Aim: To investigate the impact of palliative treatment facility volume on overall survival (OS) in patients with head and neck cancer (HNC).

Risk Factors for Plate Infection, Exposure, and Removal in Mandibular Reconstruction.

Objective: Mandibular plate reconstruction (MPR) is often indicated after tumor ablation, osteoradionecrosis excision, and traumatic bone loss to restore oral functionality and facial cosmetics. There are limited analyses identifying risk factors that lead to plate infection (PIn), exposure, and removal ("plate complications").

Study Design: Retrospective cohort study.

GLUT1 inhibitor BAY-876 induces apoptosis and enhances anti-cancer effects of bitter receptor agonists in head and neck squamous carcinoma cells.

Head and neck squamous cell carcinomas (HNSCCs) are cancers that arise in the mucosa of the upper aerodigestive tract. The five-year patient survival rate is ~50%. Treatment includes surgery, radiation, and/or chemotherapy and is associated with lasting effects even when successful in irradicating the disease.

Growth Hormone Receptor Antagonist Markedly Improves Gemcitabine Response in a Mouse Xenograft Model of Human Pancreatic Cancer.

Chemotherapy treatment against pancreatic ductal adenocarcinoma (PDAC) is thwarted by tumoral activation of multiple therapy resistance pathways. The growth hormone (GH)-GH receptor (GHR) pair is a covert driver of multimodal therapy resistance in cancer and is overexpressed in PDAC tumors, yet the therapeutic potential of targeting the same has not been explored. Here, we report that GHR expression is a negative prognostic factor in patients with PDAC.

Single-Cell View of Tumor Microenvironment Gradients in Pleural Mesothelioma.

Immunotherapies have shown great promise in pleural mesothelioma (PM), yet most patients still do not achieve significant clinical response, highlighting the importance of improving the understanding of the tumor microenvironment (TME). Here, we utilized high-throughput, single-cell RNA sequencing (scRNA-seq) to de novo identify 54 expression programs and construct a comprehensive cellular catalog of the PM TME. We found four cancer-intrinsic programs associated with poor disease outcome and a novel fetal-like, endothelial cell population that likely responds to VEGF signaling and promotes angiogenesis.

Comparing Gold-Standard Sanger Sequencing with Two Next-Generation Sequencing Platforms of HIV-1 Single Genome Amplicons.

Our goal was to assess the accuracy of next generation sequencing (NGS) compared with Sanger. We performed single genome amplification (SGA) of HIV-1 on extracted tissue DNA from two HIV+ individuals. Amplicons ( = 30) were sequenced with Sanger or reamplified with barcoded primers and pooled before sequencing using Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PB).