Single-cell RNA flow cytometry to assess intratumoral production of cytokines/chemokines.

The tumor microenvironment (TME) consists of complex interactions between cellular and extracellular components, among which the immune system is known to play an integral role in disease progression and response to therapy. Cytokines and chemokines are cell signaling proteins used by immune cells to communicate with each other as well as with other cell types in the body. These proteins control systemic and local immune responses and levels of cytokines/chemokines in the TME have been associated with tumor outcomes.

Use of optimized single-cell RNA flow cytometry protocol identifies monocytes as main producers of type I interferon in mouse syngeneic tumors.

The tumor microenvironment (TME) consists of complex interactions between cellular and extracellular components, among which the immune system is known to play an integral role in disease progression and response to therapy. Cytokines and chemokines are cell signaling proteins used by immune cells to communicate with each other as well as with other cell types in the body. These proteins control systemic and local immune responses and levels of cytokines/chemokines in the TME have been associated with tumor outcomes.

IMMUNE AND MOLECULAR CORRELATES OF RESPONSE TO IMMUNOTHERAPY REVEALED BY BRAIN-METASTATIC MELANOMA MODELS.

Despite the promising results of immune checkpoint blockade (ICB) therapy, outcomes for patients with brain metastasis (BrM) remain poor. Identifying resistance mechanisms has been hindered by limited access to patient samples and relevant preclinical models. Here, we developed two mouse melanoma BrM models that recapitulate the disparate responses to ICB seen in patients.

Factors That Impact Time to Athletic Trainer Evaluation Following Acute Injury Among Secondary School Athletes: A Report from the Athletic Trainin Practice-Based Research Network.

Context: Immediate athletic trainer (AT) availability for acute injuries is essential as worse long-term outcomes are associated with delays in receiving medical care. Several factors have been found to influence AT availability between secondary schools, but few studies have evaluated how medical coverage varies between athlete groups.

Objective: The purpose of this project was to identify factors that impact the time to AT evaluation following acute sport-related injury in secondary school setting.

In-Scanner Thoughts shape Resting-state Functional Connectivity: how participants "rest" matters.

Resting-state fMRI (rs-fMRI) scans-namely those lacking experimentally-controlled stimuli or cognitive demands-are often used to identify aberrant patterns of functional connectivity (FC) in clinical populations. To minimize interpretational uncertainty, researchers control for across-cohort disparities in age, gender, co-morbidities, and head motion. Yet, studies rarely, if ever, consider the possibility that systematic differences in inner experience (i.

CRISPR PERSIST-On enables heritable and fine-tunable human gene activation.

Current technologies for upregulation of endogenous genes use targeted artificial transcriptional activators but stable gene activation requires persistent expression of these synthetic factors. Although general "hit-and-run" strategies exist for inducing long-term silencing of endogenous genes using targeted artificial transcriptional repressors, to our knowledge no equivalent approach for gene activation has been described to date. Here we show stable gene activation can be achieved by harnessing endogenous transcription factors ( s) that are normally expressed in human cells.

MOSAIC enables saturation mutagenesis of genes and CRISPR prime editing guide RNA optimization in human cells.

CRISPR prime editing offers unprecedented versatility and precision for the installation of genetic edits . Here we describe the development and characterization of the Multiplexing Of Site-specific Alterations for Characterization ( ) method, which leverages a non-viral PCR-based prime editing method to enable rapid installation of thousands of defined edits in pooled fashion. We show that MOSAIC can be applied to perform saturation mutagenesis screens of: (1) the fusion gene, successfully identifying known and potentially new imatinib drug-resistance variants; and (2) the untranslated region (UTR), re-confirming non-coding regulatory elements involved in transcriptional initiation.

Vitamin D regulates microbiome-dependent cancer immunity.

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival.

Loss of NAT10 disrupts enhancer organization via p300 mislocalization and suppresses transcription of genes necessary for metastasis progression.

Acetylation of protein and RNA represent a critical event for development and cancer progression. NAT10 is the only known RNA acetylase that catalyzes the N4-actylcytidine (ac4C) modification of RNAs. Here, we show that the loss of NAT10 significantly decreases lung metastasis in allograft and genetically engineered mouse models of breast cancer.

Injury and Treatment Characteristics of Middle School-Aged Patients Under the Care of Athletic Trainers From 2010 to 2022: A Report From the Athletic Training Practice-Based Research Network.

Context: Exploring sports-related musculoskeletal injuries and treatment characteristics in middle school sports may help inform patient care decisions such as appropriate medical coverage.

Objective: To describe injury and treatment characteristics of middle school-aged athletes receiving care from athletic trainers within the Athletic Training Practice-Based Research Network (AT-PBRN).

Design: Descriptive study.

Virtual Reality-Based Intervention to Reduce Preoperative Anxiety in Adults Undergoing Elective Surgery: A Randomized Clinical Trial.

Importance: Preoperative anxiety is common among adult patients undergoing elective surgery and is associated with negative outcomes. Virtual reality (VR)-based interventions have been considered simpler, safer, and more effective for reducing anxiety in patients undergoing surgery than conventional care.

Objective: To examine the effectiveness of a VR-based intervention with preoperative education in reducing preoperative anxiety among adult patients undergoing elective surgery.

Manifold learning for fMRI time-varying functional connectivity.

Whole-brain functional connectivity () measured with functional MRI (fMRI) evolves over time in meaningful ways at temporal scales going from years (e.g., development) to seconds [e.

Distinct brain-wide presynaptic networks underlie the functional identity of individual cortical neurons.

Neuronal connections provide the scaffolding for neuronal function. Revealing the connectivity of functionally identified individual neurons is necessary to understand how activity patterns emerge and support behavior. Yet, the brain-wide presynaptic wiring rules that lay the foundation for the functional selectivity of individual neurons remain largely unexplored.

Manifold Learning for fMRI time-varying FC.

Whole-brain functional connectivity ( ) measured with functional MRI (fMRI) evolve over time in meaningful ways at temporal scales going from years (e.g., development) to seconds (e.

Patient-reported outcome measures as an outcome variable in sports medicine research.

Injury prevention and rehabilitation research often address variables that would be considered clinician-oriented outcomes, such as strength, range of motion, laxity, and return-to-sport. While clinician-oriented variables are helpful in describing the physiological recovery from injury, they neglect the patient perspective and aspects of patient-centered care. Variables that capture patient perspective are essential when considering the impact of injury and recovery on the lives of patients.

Patient-Reported Outcomes at Return to Sport After Lateral Ankle Sprain Injuries: A Report From the Athletic Training Practice-Based Research Network.

Context: Limited evidence exists regarding the assessment of single-item patient-reported outcomes when patients are medically cleared to return to sport after a lateral ankle sprain (LAS) injury.

Objective: To evaluate self-reports of improvement in health status, pain, function, and disability at return to sport after an LAS.

Design: Descriptive study.

Characterizing athletic healthcare: A perspective on methodological challenges, lessons learned, and paths forward.

Recently, there has been an emphasis on collecting large datasets in the field of sports medicine. While there have been great advances in areas of sport performance and sport epidemiology, there have been fewer efforts dedicated to understanding the effectiveness and impact of athletic healthcare, including injury prevention programs and rehabilitation interventions provided at the point-of-care. In 2009, the Athletic Training Practice-Based Research Network (AT-PBRN) was launched to address this need, with the mission of improving the quality of care provided by athletic trainers.

Characterization of regional variation of bone mineral density in the geriatric human cervical spine by quantitative computed tomography.

Background: Odontoid process fractures are among the most common in elderly cervical spines. Their treatment often requires fixation, which may include use of implants anteriorly or posteriorly. Bone density can significantly affect the outcomes of these procedures.

Spatial differentiation and determinants of COVID-19 in Indonesia.

Background: The spread of the coronavirus disease 2019 (COVID-19) has increasingly agonized daily lives worldwide. As an archipelagic country, Indonesia has various physical and social environments, which implies that each region has a different response to the pandemic. This study aims to analyze the spatial differentiation of COVID-19 in Indonesia and its interactions with socioenvironmental factors.

A bibliometric review on the inter-connection between climate change and rice farming.

Rice is an important cereal and a staple food in many countries in the world. Climate change is a significant challenge that affects paddy production and threatens food security. However, research and development in this area continue to work to ensure the supply of rice fulfils the demands of the population.

A Phase IIIb Open-Label, Single-Arm Study of Afatinib in EGFR TKI-Naïve Patients with EGFRm+ NSCLC: Final Analysis, with a Focus on Patients Enrolled at Sites in China.

Background: Afatinib has been shown as a suitable option for the treatment of epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC) in randomized controlled trials. However, patients treated in real-world clinical practice, including elderly patients, and those with brain metastases or poor Eastern Cooperative Oncology Group (ECOG) performance statuses, are often excluded from these studies.

Objective: To report the final results, with a particular focus on patients enrolled in China, from a prospective phase IIIb, "near real-world" study of afatinib in tyrosine kinase inhibitor (TKI)-naïve Asian patients with EGFRm+ NSCLC.

The Critical Need for Advanced Training in Electronic Records Use: Implications for Clinical Practice, Education, and the Advancement of Athletic Training.

Context: The effective use of electronic records (ie, electronic health records or electronic medical records) is essential to professional initiatives and the overall advancement of the athletic training profession. However, evidence suggests that comprehensive patient care documentation and widespread use of electronic records are still limited in athletic training. The lack of formal training and education for clinicians and students is often cited as a primary barrier to electronic record use.

Can gut microbes predict efficacy and toxicity of combined immune checkpoint blockade?

A recent report in Nature Medicine pinpoints a role for gut microbiota in response and toxicity to combined immune checkpoint blockade targeting CTLA-4 and PD-1. This emergent study provides insights that can be used to leverage microbiota in the design of anticancer therapies to mitigate toxicity while enhancing efficacy.