Differences in tumor-associated T-cell receptor repertoires between early-onset and average-onset colorectal cancer.

The incidence of colorectal cancer (CRC) among individuals younger than age 50 (early-onset CRC [EOCRC]) has substantially increased, and yet the etiology and molecular mechanisms underlying this alarming rise remain unclear. We compared tumor-associated T-cell repertoires between EOCRC and average-onset CRC (AOCRC) to uncover potentially unique immune microenvironment-related features by age of onset. Our discovery cohort included 242 patients who underwent surgical resection at Cleveland Clinic from 2000 to 2020.

Germline genetic regulation of the colorectal tumor immune microenvironment.

Objective: To evaluate the contribution of germline genetics to regulating the briskness and diversity of T cell responses in CRC, we conducted a genome-wide association study to examine the associations between germline genetic variation and quantitative measures of T cell landscapes in 2,876 colorectal tumors from participants in the Molecular Epidemiology of Colorectal Cancer Study (MECC).

Methods: Germline DNA samples were genotyped and imputed using genome-wide arrays. Tumor DNA samples were extracted from paraffin blocks, and T cell receptor clonality and abundance were quantified by immunoSEQ (Adaptive Biotechnologies, Seattle, WA).

Perioperative management of a double valve replacement and coronary artery bypass graft in a patient with carcinoid syndrome; a case report and literature review.

Introduction: Carcinoid tumors are rare neuroendocrine tumors; about 5% of patients develop the carcinoid syndrome. We present the case of a patient with carcinoid syndrome undergoing cardiac surgery.

Case Report: A 74-year-old patient with carcinoid heart disease and hepatic metastases underwent double valve replacement and CABG.

Heterozygote advantage at HLA class I and II loci and reduced risk of colorectal cancer.

Objective: Reduced diversity at Human Leukocyte Antigen (HLA) loci may adversely affect the host's ability to recognize tumor neoantigens and subsequently increase disease burden. We hypothesized that increased heterozygosity at HLA loci is associated with a reduced risk of developing colorectal cancer (CRC).

Methods: We imputed HLA class I and II four-digit alleles using genotype data from a population-based study of 5,406 cases and 4,635 controls from the Molecular Epidemiology of Colorectal Cancer Study (MECC).

Carbohydrate Intake Prior to Oral Glucose Tolerance Testing.

With the emergence of glycated hemoglobin as a diagnostic test for diabetes, oral glucose tolerance tests (OGTTs) have become rare in endocrinology practice. As they have moved out of favor, the importance of patient instructions on preparation prior to OGTT has faded from memory. Decades-old literature, well-known to endocrinologists a generation ago, emphasized the importance of carbohydrate intake prior to OGTT.

Cone beam computed tomography for dose calculation quality assurance for magnetic resonance-only radiotherapy.

Background And Purpose: Magnetic Resonance (MR)-only prostate radiotherapy using synthetic Computed Tomography (sCT) algorithms with high dose accuracy has been clinically implemented. MR images can suffer from geometric distortions so Quality Assurance (QA) using an independent, geometrically accurate, image could be required. The first-fraction Cone Beam CT (CBCT) has demonstrated potential but has not been evaluated in a clinical MR-only pathway.

Experimental increase of blood glucose alters resting state EEG measures of excitation-inhibition balance.

New Findings: What is the central question of this study? Glucose is the dominant energy source for the brain. However, little is known about how glucose metabolism impacts the coordination of network activity in the brain in healthy adults. What is the main finding and its importance? We demonstrate that both α oscillations and the aperiodic signal components of the resting EEG are modulated by experimentally elevated blood glucose concentrations.

Technical Note: Efficient and accurate MRI-only based treatment planning of the prostate using bulk density assignment through atlas-based segmentation.

Purpose: This study investigates the dosimetric accuracy as well as the robustness of a bulk density assignment approach to magnetic resonance imaging (MRI)-only based treatment planning of the prostate, with bulk density regions automatically identified using atlas-based segmentation (ABS).

Methods: Twenty prostate radiotherapy patients received planning computed tomography (CT) and MRI scans and were treated with volumetric modulated arc therapy (VMAT). Two bulk densities were set, one for bone and one for soft tissue.

Intact Auditory Cortical Cross-Frequency Coupling in Early and Chronic Schizophrenia.

Background: Previous work has identified a hierarchical organization of neural oscillations that supports performance of complex cognitive and perceptual tasks, and can be indexed with phase-amplitude coupling (PAC) between low- and high-frequency oscillations. Our aim was to employ enhanced source localization afforded by magnetoencephalography (MEG) to expand on earlier reports of intact auditory cortical PAC in schizophrenia and to investigate how PAC may evolve over the early and chronic phases of the illness.

Methods: Individuals with early schizophrenia (n=12) (≤5 years of illness duration), chronic schizophrenia (n=16) (>5 years of illness duration) and healthy comparators (n = 17) performed the auditory steady state response (ASSR) to 40, 30, and 20 Hz stimuli during MEG recordings.

Gene Expression in Patient-Derived Neural Progenitors Implicates WNT5A Signaling in the Etiology of Schizophrenia.

Background: Genome-wide association studies of schizophrenia have demonstrated that variations in noncoding regions are responsible for most of the common variation heritability of the disease. It is hypothesized that these risk variants alter gene expression. Therefore, studying alterations in gene expression in schizophrenia may provide a direct approach to understanding the etiology of the disease.

Loss-of-function mutation in inositol monophosphatase 1 (IMPA1) results in abnormal synchrony in resting-state EEG.

Background: Dysregulation of the inositol cycle is implicated in a wide variety of human diseases, including developmental defects and neurological diseases. A homozygous frameshift mutation in IMPA1, coding for the enzyme inositol monophosphatase 1 (IMPase), has recently been associated with severe intellectual disability (ID) in a geographically isolated consanguineous family in Northeastern Brazil (Figueredo et al., 2016).

Serum anticholinergicity is associated with reduced prefrontal brain function in early course schizophrenia.

Increased anticholinergic activity resulting from pharmacotherapies used to treat schizophrenia is associated with poorer cognition. However the neural mechanisms underlying this effect are unknown. In this study of 39 early course schizophrenia outpatients, we demonstrate that increased serum anticholinergic activity is associated with reduced activation across the prefrontal cortex, including the dorsolateral, anterior, and medial prefrontal cortices, during two tasks of cognitive control.

Assessing characteristics of RNA amplification methods for single cell RNA sequencing.

Background: Recently, measurement of RNA at single cell resolution has yielded surprising insights. Methods for single-cell RNA sequencing (scRNA-seq) have received considerable attention, but the broad reliability of single cell methods and the factors governing their performance are still poorly known.

Results: Here, we conducted a large-scale control experiment to assess the transfer function of three scRNA-seq methods and factors modulating the function.

Development of sensory gamma oscillations and cross-frequency coupling from childhood to early adulthood.

Given the importance of gamma oscillations in normal and disturbed cognition, there has been growing interest in their developmental trajectory. In the current study, age-related changes in sensory cortical gamma were studied using the auditory steady-state response (ASSR), indexing cortical activity entrained to a periodic auditory stimulus. A large sample (n = 188) aged 8-22 years had electroencephalography recording of ASSR during 20-, 30-, and 40-Hz click trains, analyzed for evoked amplitude, phase-locking factor (PLF) and cross-frequency coupling (CFC) with lower frequency oscillations.

Impact of concomitant coronary artery bypass grafting on in-hospital outcome in octogenarians undergoing aortic valve replacement.

Background And Aim Of The Study: Abundant data are available reporting excellent in-hospital outcomes after surgical aortic valve replacement (AVR) in octogenarians. However, there is a paucity of studies reporting the in-hospital outcome of concomitant AVR and coronary artery bypass grafting (CABG) in this group of patients. Hence, a comparison was made of the impact of concomitant AVR and CABG versus isolated AVR on in-hospital outcome in octogenarians.

Concomitant off-pump coronary artery bypass grafting results in improved in-hospital outcomes for patients with ischemic mitral regurgitation undergoing surgery.

Objective: Surgical management of ischemic mitral regurgitation (IMR) has primarily consisted of revascularization with or without the addition of mitral valve repair or replacement. We hypothesize that performing off-pump coronary artery bypass (OPCAB) grafting before fixing MR improves in-hospital outcomes for patients with IMR undergoing surgery.

Methods: From January 2000 through December 2010, a total of 96 consecutive patients with moderate or severe IMR, as determined by preoperative echocardiography, underwent on-pump coronary artery bypass grafting (CABG) (n = 66) or OPCAB (n = 30) revascularization with concomitant mitral valve repair or replacement.

In-hospital outcomes of pedicled bilateral internal mammary artery use in diabetic and nondiabetic patients undergoing off-pump coronary artery bypass grafting: single-surgeon, single-center experience.

Objective: A common perception is that use of pedicled bilateral internal mammary arteries (BIMA) increases the risk of sternal wound complications in diabetic patients undergoing coronary artery bypass grafting (CABG). The purpose of this study was to compare the in-hospital outcomes of CABG using pedicled BIMA in diabetic and nondiabetic patients.

Methods: From September 1998 to September 2010, 390 consecutive diabetic patients and 519 nondiabetic patients underwent isolated off-pump CABG using pedicled BIMA.

Dopamine and gamma band synchrony in schizophrenia--insights from computational and empirical studies.

Dopamine modulates cortical circuit activity in part through its actions on GABAergic interneurons, including increasing the excitability of fast-spiking interneurons. Though such effects have been demonstrated in single cells, there are no studies that examine how such mechanisms may lead to the effects of dopamine at a neural network level. With this motivation, we investigated the effects of dopamine on synchronization in a simulated neural network composed of excitatory and fast-spiking inhibitory Wang-Buzsaki neurons.

Ten-year outcome analysis of off-pump sequential grafting: single surgeon, single center experience.

Objectives: Despite increasing recognition that off-pump coronary artery bypass surgery and sequential grafting strategy individually are associated with improved outcomes, concerns persist regarding the safety and efficacy of combining these 2 techniques. We compared in-hospital and midterm outcomes for off-pump multivessel sequential and conventional coronary artery bypass grafting.

Methods: From September 1998 to September 2008, 689 consecutive patients received off-pump multivessel sequential coronary artery bypass grafting performed by a single surgeon.