Molecular Features of Diffuse Large B-Cell Lymphoma Associated With Primary Treatment Resistance.

Diffuse large B-cell lymphoma (DLBCL) patients that fail to achieve a complete metabolic response with frontline immunochemotherapy have a poor prognosis. Genomic profiling has led to a broader understanding of the molecular drivers in DLBCL, but it is unknown how well current classifiers identify patients that will experience primary treatment resistance (PTR). Using whole exome and RNA sequencing data from newly diagnosed DLBCL patients, we evaluated the genomic landscape of PTR and compared it to that of non-PTR DLBCL.

DEK regulates B-cell proliferative capacity and is associated with aggressive disease in low-grade B-cell lymphomas.

This study sheds light on the pivotal role of the oncoprotein DEK in B-cell lymphoma. We reveal DEK expression correlates with increased tumor proliferation and inferior overall survival in cases diagnosed with low-grade B-cell lymphoma (LGBCL). We also found significant correlation between DEK expression and copy number alterations in LGBCL tumors, highlighting a novel mechanism of LGBCL pathogenesis that warrants additional exploration.

Physiological carry-over effects of variable precipitation are mediated by reproductive status in a long-lived ungulate.

In the age of global climate change, extreme climatic events are expected to increase in frequency and severity. Animals will be forced to cope with these novel stressors in their environment. Glucocorticoids (i.

National Athletic Trainers' Association Position Statement: Emergency Action Plan Development and Implementation in Sport.

Objective: An emergency action plan (EAP) is a written document detailing the preparations and on-site emergency response of health care professionals and other stakeholders to medical emergencies in the prehospital setting. The EAP is developed to address any type of catastrophic injury response and should not be condition specific. The objective of this National Athletic Trainers' Association position statement is to provide evidence-based and consensus-based recommendations for developing and implementing an EAP for sports settings.

Impact of anesthesia on micromagnetic stimulation (MS) of the vagus nerve.

To treat diseases associated with vagal nerve control of peripheral organs, it is necessary to selectively activate efferent and afferent fibers in the vagus. As a result of the nerve's complex anatomy, fiber-specific activation proves challenging. Spatially selective neuromodulation using micromagnetic stimulation(MS) is showing incredible promise.

Follicular lymphoma B cells exhibit heterogeneous transcriptional states with associated somatic alterations and tumor microenvironments.

Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma of germinal center origin, which presents with significant biologic and clinical heterogeneity. Using RNA-seq on B cells sorted from 87 FL biopsies, combined with machine-learning approaches, we identify 3 transcriptional states that divide the biological ontology of FL B cells into inflamed, proliferative, and chromatin-modifying states, with relationship to prior GC B cell phenotypes. When integrated with whole-exome sequencing and immune profiling, we find that each state was associated with a combination of mutations in chromatin modifiers, copy-number alterations to TNFAIP3, and T follicular helper cells (Tfh) cell interactions, or primarily by a microenvironment rich in activated T cells.

The Clinical Anatomy Fellowship: Revolutionizing curricular experiences for faculty and students.

Fellows completing the Clinical Anatomy Fellowship at Kansas City University assist Anatomy faculty in the Gross Anatomy laboratory, complete robust research projects, and support other departments. The program's positive impact on participants has been reported; however, the impact on individuals interfacing with Fellows has not been investigated. A follow-up, survey-based (Likert scale, multiple-choice, open-ended) study was conducted to evaluate faculty, staff, and student perceptions of the program.

Autoantibodies, antigen-autoantibody complexes and antigens complement CA125 for early detection of ovarian cancer.

Background: Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer.

Methods: Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone.

Results: Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity.

The clinical anatomy fellowship: A participants' perspective.

Kansas City University offers a Clinical Anatomy Fellowship which enrolls nine medical students during each academic year and provides training in research, teaching, and advanced anatomical topics. The Fellows practice as novice educators, working alongside Anatomy faculty to teach medical students in the Gross Anatomy laboratory. However, little has been reported related to Fellowship participation and success outcomes.

Molecular classification and identification of an aggressive signature in low-grade B-cell lymphomas.

Non-follicular low-grade B-cell lymphomas (LGBCL) are biologically diverse entities that share clinical and histologic features that make definitive pathologic categorization challenging. While most patients with LGBCL have an indolent course, some experience aggressive disease, highlighting additional heterogeneity across these subtypes. To investigate the potential for shared biology across subtypes, we performed RNA sequencing and applied machine learning approaches that identified five clusters of patients that grouped independently of subtype.

The feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II-III and metastatic breast cancers.

Purpose: The antigenic targets of immunity and the role of vaccination in breast cancer are unknown. We performed a phase I study of an autologous GM-CSF-secreting breast cancer vaccine in patients with metastatic and stage II-III breast cancer.

Methods: Tumor cells from patients with metastatic (n = 15) and stage II-III (n = 7) disease were transduced with a replication-defective adenoviral vector encoding GM-CSF, and then irradiated.

Screening for HPV-related oropharyngeal, anal, and penile cancers in middle-aged men: Initial report from the HOUSTON clinical trial.

Background: The Human papillomavirus (HPV)-related Oropharyngeal and Uncommon Cancers Screening Trial of Men (HOUSTON) was designed to determine the prevalence of IgG antibodies to HPV type 16 E proteins (HPV16EAbs), to screen for persistence of HPV and/or detect HPV-related premalignancies and cancers, and to assess acceptance of screening among middle-aged men.

Methods: HOUSTON consists of a cross-sectional study and a longitudinal cohort study of men aged 50-64 years. Serologic HPV16EAb status and oral rinse HPV16 status were determined.

Laser ablation of the pia mater for insertion of high-density microelectrode arrays in a translational sheep model.

. The safe insertion of high density intracortical electrode arrays has been a long-standing practical challenge for neural interface engineering and applications such as brain-computer interfaces (BCIs). However, the pia mater can be difficult to penetrate and causes deformation of underlying cortical tissue during insertion of high-density intracortical arrays.

Improving Accuracy of Texture-Modified Diets and Thickened Fluids Provision in the Hospital: Evidence in Action.

Ensuring inpatients with dysphagia receive and consume the correct texture-modified diet and thickened fluid prescriptions is challenging, and errors can result in significant complications for patients and increased costs to hospitals. The aim of this study was to investigate underlying factors that help or hinder receipt and consumption of correct dietary prescriptions for people with dysphagia in the hospital setting then implement and evaluate a range of strategies to address identified issues. A mixed-methods study design, using an integrated knowledge translation approach, was conducted in three phases.

The Argo: a high channel count recording system for neural recording in vivo.

Objective: Decoding neural activity has been limited by the lack of tools available to record from large numbers of neurons across multiple cortical regions simultaneously with high temporal fidelity. To this end, we developed the Argo system to record cortical neural activity at high data rates.

Approach: Here we demonstrate a massively parallel neural recording system based on platinum-iridium microwire electrode arrays bonded to a CMOS voltage amplifier array.

Roundtable on Preseason Heat Safety in Secondary School Athletics: Prehospital Care of Patients With Exertional Heat Stroke.

Objective: First, we will update recommendations for the prehospital management and care of patients with exertional heat stroke (EHS) in the secondary school setting. Second, we provide action items to aid clinicians in developing best-practice documents and policies for EHS. Third, we supply practical strategies clinicians can use to implement best practice for EHS in the secondary school setting.

When worry is excessive: Easing the burden of GAD.

A stepped approach to management using these communication tips and coping strategies can help decrease the stigma of generalized anxiety disorder and increase patients' sense of ownership in their care.

Relative Selectivity of Covalent Inhibitors Requires Assessment of Inactivation Kinetics and Cellular Occupancy: A Case Study of Ibrutinib and Acalabrutinib.

Kinases form an attractive class of targets for small molecule inhibitors, but similarity among their adenosine triphosphate binding sites presents difficulties for developing selective drugs. Standard methods of evaluating selectivity of most reversibly bound drugs account for binding affinity but not the two-step process, affinity and inactivation, occurring during covalent inhibition. To illustrate this concept, we assessed the selectivity of Bruton's tyrosine kinase (BTK) over TEC kinases by two novel therapeutics: ibrutinib and acalabrutinib.

Patient use of an online triage platform: a mixed-methods retrospective exploration in UK primary care.

Background: Recent years have seen the introduction of online triage allowing patients to describe their problem via an online form. Subsequently, a GP telephones the patient, conducting a telephone consultation or arranging a face-to-face consultation.

Aim: This study aimed to explore patterns-of-use and patients' experiences of using an online triage system.

Small-Group Activity to Reinforce the Impact of Valvular Defects and Heart Failure on Cardiac Pressure-Volume Relationships.

Introduction: An important topic in cardiac physiology is the relationship between changes in intracardiac pressures and volumes during the cardiac cycle. This topic lends itself well to utilizing active learning principles to facilitate student understanding of pressure and volume changes in normal cardiac physiology and in the pathophysiology of valve disease and heart failure. We describe an active learning exercise regarding this topic that engages and facilitates student learning in a small-group setting.

Student engagement and higher order skill proficiency: a comparison of traditional didactic and renewed integrated active learning curricula.

A large, multicampus, public medical school underwent curricular renewal, emphasizing a student-centered approach with 50% of all course contact time devoted to active learning. Determining the impact of active learning on student engagement and higher order skill (HOS) proficiency was the primary aim of this study. Following Institutional Review Board approval, two cohort groups of first-year medical students were enrolled.

Engagement and higher order skill proficiency of students completing a medical physiology course in three diverse learning environments.

The primary aim of this study was to determine whether levels of student engagement, higher order skill proficiency, and knowledge acquisition demonstrated by medical students would differ when completing the same course in three diverse learning environments. Following Institutional Review Board approval, 56 first-year medical students, registered at the same medical school but attending class at three different campus centers, were enrolled in the study. All participants were completing a medical physiology course that utilized the same learning objectives but relied on different faculty incorporating diverse methodologies (percentage of class devoted to active learning strategies), course format (6-wk block vs.