Impact of Tobacco, Marijuana, and Alcohol Use on Overall Survival in Recurrent Metastatic Head and Neck Cancer Patients Treated With Immune Checkpoint Inhibitors.

Aim: The response rates to immune checkpoint inhibitors (ICI) remain low (13%-20%) in metastatic head and neck cancer patients, indicating an urgent need to better understand factors predictive of response to these agents. This study explored the impact of smoking status, marijuana use, and alcohol consumption on treatment outcomes in recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients treated with ICI.

Methods: A retrospective analysis was performed on 201 R/M HNSCC patients treated with ICI between January 15th 2016 and April 9th 2020 at a single institution.

Sintilimab plus HPV vaccine for recurrent or metastatic cervical cancer.

Purpose: Recurrent or metastatic cervical cancer (r/m CC) presents limited treatment options for patients failed or progressed quickly following first-line therapy. This study investigated the potential of sintilimab with a prophylactic human papillomavirus (HPV) quadrivalent vaccine as a second-line treatment for r/m CC.

Methods: In this phase 2 clinical trial, patients with r/m CC previously unresponsive or intolerant to standard treatments for metastatic or recurrent lesions were enrolled.

Development of a prognostic signature for overall survival using peripheral blood biomarkers in head and neck squamous cell carcinoma treated with immune checkpoint inhibitors.

Background: We previously reported in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs), pretreatment higher lactate dehydrogenase (LDH) and absolute (abx) neutrophils as well as lower percent (%) lymphocytes correlated with worse overall survival (OS). In this study we aimed to develop a prognostic signature for HNSCC treated with ICIs using these peripheral blood biomarkers (PBBMs).

Methods: Adults with R/M HNSCC treated with ICIs at our institution from 08/2012 to 03/2021 with pretreatment PBBMs were included.

Precise genetic control of ATOH1 enhances maturation of regenerated hair cells in the mature mouse utricle.

Vestibular hair cells are mechanoreceptors critical for detecting head position and motion. In mammals, hair cell loss causes vestibular dysfunction as spontaneous regeneration is nearly absent. Constitutive expression of exogenous ATOH1, a hair cell transcription factor, increases hair cell regeneration, however, these cells fail to fully mature.

The efficacy of first and second immunotherapy exposure in patients with recurrent or metastatic cervical cancer.

Objective: Immunotherapy has led to changes in cervical cancer guidelines. Therefore, additional biomarkers to identify the ideal patient who would experience the most benefit may be important.

Methods: We retrospectively collected 208 patients with R/M CC and recorded clinicopathologic information, peripheral blood markers and treatments to analyze the prognostic factors of clinical outcomes.

Improved outcomes of palliative radiotherapy combined with immune checkpoint inhibitors in recurrent or metastatic cervical cancers.

Background: Immunotherapy provides a remarkable survival advantage for patients with recurrent or metastatic cervical cancer (R/M CC). However, the role of immunotherapy in combination with radiotherapy in R/M CC remains unclear.

Methods: We retrospectively analyzed factors affecting immunotherapy effectiveness in patients with R/M CC.

Assessing the Performance of Models from the 2022 RSNA Cervical Spine Fracture Detection Competition at a Level I Trauma Center.

Purpose To evaluate the performance of the top models from the RSNA 2022 Cervical Spine Fracture Detection challenge on a clinical test dataset of both noncontrast and contrast-enhanced CT scans acquired at a level I trauma center. Materials and Methods Seven top-performing models in the RSNA 2022 Cervical Spine Fracture Detection challenge were retrospectively evaluated on a clinical test set of 1828 CT scans (from 1829 series: 130 positive for fracture, 1699 negative for fracture; 1308 noncontrast, 521 contrast enhanced) from 1779 patients (mean age, 55.8 years ± 22.

The Restriction Activity Investigation of Rv2528c, an Mrr-like Modification-Dependent Restriction Endonuclease from .

(), as a typical intracellular pathogen, possesses several putative restriction-modification (R-M) systems, which restrict exogenous DNA's entry, such as bacterial phage infection. Here, we investigate Rv2528c, a putative Mrr-like type IV restriction endonuclease (REase) from H37Rv, which is predicted to degrade methylated DNA that contains m6A, m5C, etc. Rv2528c shows significant cytotoxicity after being expressed in BL21(DE3)pLysS strain.

Genetic ablation of adhesion ligands mitigates rejection of allogeneic cellular immunotherapies.

Allogeneic cellular immunotherapies hold promise for broad clinical implementation but face limitations due to potential rejection of donor cells by the host immune system. Silencing of beta-2 microglobulin (B2M) expression is commonly employed to evade T cell-mediated rejection by the host, although the absence of B2M is expected to trigger missing-self responses by host natural killer (NK) cells. Here, we demonstrate that genetic deletion of the adhesion ligands CD54 and CD58 in B2M-deficient chimeric antigen receptor (CAR) T cells and multi-edited induced pluripotent stem cell (iPSC)-derived CAR NK cells reduces their susceptibility to rejection by host NK cells in vitro and in vivo.

CD28 Costimulation Augments CAR Signaling in NK Cells via the LCK/CD3ζ/ZAP70 Signaling Axis.

Multiple factors in the design of a chimeric antigen receptor (CAR) influence CAR T-cell activity, with costimulatory signals being a key component. Yet, the impact of costimulatory domains on the downstream signaling and subsequent functionality of CAR-engineered natural killer (NK) cells remains largely unexplored. Here, we evaluated the impact of various costimulatory domains on CAR-NK cell activity, using a CD70-targeting CAR.

Pixel-Level Recognition of Trace Mycotoxins in Red Ginseng Based on Hyperspectral Imaging Combined with 1DCNN-Residual-BiLSTM-Attention Model.

Red ginseng is widely used in food and pharmaceuticals due to its significant nutritional value. However, during the processing and storage of red ginseng, it is susceptible to grow mold and produce mycotoxins, generating security issues. This study proposes a novel approach using hyperspectral imaging technology and a 1D-convolutional neural network-residual-bidirectional-long short-term memory attention mechanism (1DCNN-ResBiLSTM-Attention) for pixel-level mycotoxin recognition in red ginseng.

Evaluation of hemostatic, anti-inflammatory, wound healing, skin irritation and allergy, and antimicrobial properties of active fraction from the ethanol extract of Chromolaena odorata (L.) R.M. King & H. Rob.

Ethnopharmacological Relevance: Chromolaenaodorata (L.) R.M.

Isolation, Expansion, and Endoscopic Delivery of Autologous Enteric Neuronal Stem Cells in Swine.

The enteric nervous system (ENS) is an extensive network of neurons and glia within the wall of the gastrointestinal (GI) tract that regulates many essential GI functions. Consequently, disorders of the ENS due to developmental defects, inflammation, infection, or age-associated neurodegeneration lead to serious neurointestinal diseases. Despite the prevalence and severity of these diseases, effective treatments are lacking as they fail to directly address the underlying pathology.

Obesity-Related Biomarkers Are Associated With Exercise Intolerance and HFpEF.

Background: Obesity and adiposity are associated with an increased risk of heart failure with preserved ejection fraction (HFpEF); yet, specific underlying mechanisms remain unclear. We sought to examine the association of obesity-related biomarkers including adipokines (leptin, resistin, adiponectin), inflammatory markers (CRP [C-reactive protein], IL-6 [interleukin-6]), and insulin resistance (HOMA-IR) with HFpEF status, exercise capacity, and cardiovascular outcomes.

Methods: We studied 509 consecutive patients with left ventricular ejection fraction ≥50% and chronic dyspnea, who underwent clinically indicated cardiopulmonary exercise test with invasive hemodynamic monitoring between 2006 and 2017.

Transplanted ENSCs form functional connections with intestinal smooth muscle and restore colonic motility in nNOS-deficient mice.

Background: Enteric neuropathies, which result from abnormalities of the enteric nervous system, are associated with significant morbidity and high health-care costs, but current treatments are unsatisfactory. Cell-based therapy offers an innovative approach to replace the absent or abnormal enteric neurons and thereby restore gut function.

Methods: Enteric neuronal stem cells (ENSCs) were isolated from the gastrointestinal tract of Wnt1-Cre;R26tdTomato mice and generated neurospheres (NS).

Differential Efficacy of Small Molecules Dynasore and Mdivi-1 for the Treatment of Dry Eye Epitheliopathy or as a Countermeasure for Nitrogen Mustard Exposure of the Ocular Surface.

The ocular surface comprises the wet mucosal epithelia of the cornea and conjunctiva, the associated glands, and the overlying tear film. Epitheliopathy is the common pathologic outcome when the ocular surface is subjected to oxidative stress. Whether different stresses act via the same or different mechanisms is not known.

Cost-Effectiveness Analysis of Ga-DOTATATE PET/MRI in Radiotherapy Planning in Patients with Intermediate-Risk Meningioma.

Background And Purpose: While contrast-enhanced MR imaging is the criterion standard in meningioma diagnosis and treatment response assessment, gallium Ga-DOTATATE PET/MR imaging has increasingly demonstrated utility in meningioma diagnosis and management. Integrating Ga-DOTATATE PET/MR imaging in postsurgical radiation planning reduces the planning target volume and organ-at-risk dose. However, Ga-DOTATATE PET/MR imaging is not widely implemented in clinical practice due to higher perceived costs.

IRIS: Discovery of cancer immunotherapy targets arising from pre-mRNA alternative splicing.

Alternative splicing (AS) is prevalent in cancer, generating an extensive but largely unexplored repertoire of novel immunotherapy targets. We describe soform peptides from NA splicing for mmunotherapy target creening (IRIS), a computational platform capable of discovering AS-derived tumor antigens (TAs) for T cell receptor (TCR) and chimeric antigen receptor T cell (CAR-T) therapies. IRIS leverages large-scale tumor and normal transcriptome data and incorporates multiple screening approaches to discover AS-derived TAs with tumor-associated or tumor-specific expression.

Are All Patients Going Home after Total Knee Arthroplasty? A Temporal Analysis of Discharge Trends and Predictors of Nonhome Discharge (2011-2020).

Value-based orthopaedic surgery and reimbursement changes for total knee arthroplasty (TKA) are potential factors shaping arthroplasty practice nationwide. This study aimed to evaluate (1) trends in discharge disposition (home vs nonhome discharge), (2) episode-of-care outcomes for home and nonhome discharge cohorts, and (3) predictors of nonhome discharge among patients undergoing TKA from 2011 to 2020. The National Surgical Quality Improvement Program database was reviewed for all primary TKAs from 2011 to 2020.

Neoantigen-targeted CD8 T cell responses with PD-1 blockade therapy.

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells. The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy.

Efficacy and safety of KL-A167 in previously treated recurrent or metastatic nasopharyngeal carcinoma: a multicenter, single-arm, phase 2 study.

Background: KL-A167 is a fully humanized monoclonal antibody targeting programmed cell death-ligand 1. This phase 2 study aimed to evaluate the efficacy and safety of KL-A167 in Chinese patients with previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC).

Methods: This was a multicentre, single-arm, phase 2 study of KL-A167 in R/M NPC (KL167-2-05-CTP) (NCT03848286), conducted at 42 hospitals across the People's Republic of China.

Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors.

Background: Little is known regarding associations between peripheral blood biomarkers (PBBMs) and survival, response, and toxicity in recurrent/metastatic head and neck squamous cell carcinomas (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs).

Methods: In this single-institution retrospective cohort study, a dataset of patients with R/M HNSCC treated with ICIs between 08/2012-03/2021 was established, including demographic and clinicopathologic characteristics. Pretreatment PBBMs were collected and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv5, objective response (ORR) by RECIST 1.