Medicine and Health Sciences Commons^™

Differences In The Link Between Social Trait Judgment And Socio-Emotional Experience In Neurotypical And Autistic Individuals, Shangcheng Zhao, Runnan Cao, Chujun Lin, Shuo Wang, Hongbo Yu

2020-Current year OA Pubs

Neurotypical (NT) individuals and individuals with autism spectrum disorder (ASD) make different judgments of social traits from others' faces; they also exhibit different social emotional responses in social interactions. A common hypothesis is that the differences in face perception in ASD compared with NT is related to distinct social behaviors. To test this hypothesis, we combined a face trait judgment task with a novel interpersonal transgression task that induces measures social emotions and behaviors. ASD and neurotypical participants viewed a large set of naturalistic facial stimuli while judging them on a comprehensive set of social traits (e.g., warm, charismatic, critical). …

Associations Of Geographic-Based Socioeconomic Factors And Hpv Vaccination Among Male And Female Children In Five Us States, Serena Xiong, Sarah Humble, Alan Barnette, Heather Brandt, Vetta Thompson, Lisa M Klesges, Michelle I Silver

2020-Current year OA Pubs

BACKGROUND: We assessed whether five geographic-based socioeconomic factors (medically underserved area (MUA); healthcare provider shortage area (HPSA); persistent poverty; persistent child poverty; and social vulnerability index (SVI)) were associated with the odds of HPV vaccination initiation, series completion, and parental vaccine hesitancy, and whether the observed relationships varied by gender of the child.

METHODS: An online panel service, administered through Qualtrics®, was used to recruit parents of adolescents 9-17 years of age to complete a one-time survey in 2021. Coverage of the panel included five US states: Arkansas, Mississippi, Missouri, Tennessee, and Southern Illinois. Generalized estimating equation (GEE) models were …

Dual Membrane-Spanning Anti-Sigma Factors Regulate Vesiculation In Bacteroides Thetaiotaomicron, Evan J Pardue, Mariana G Sartorio, Biswanath Jana, Nichollas E Scott, Wandy L Beatty, Juan C Ortiz-Marquez, Tim Van Opijnen, Fong-Fu Hsu, Robert F Potter, Mario F Feldman

2020-Current year OA Pubs

Bacteroidota are abundant members of the human gut microbiota that shape the enteric landscape by modulating host immunity and degrading dietary- and host-derived glycans. These processes are mediated in part by

Proteomic Associations Of Adverse Outcomes In Human Heart Failure, Marie-Joe Dib, Ahmed Diab, Ali Javaheri, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: Identifying novel molecular drivers of disease progression in heart failure (HF) is a high-priority goal that may provide new therapeutic targets to improve patient outcomes. The authors investigated the relationship between plasma proteins and adverse outcomes in HF and their putative causal role using Mendelian randomization.

METHODS AND RESULTS: The authors measured 4776 plasma proteins among 1964 participants with HF with a reduced left ventricular ejection fraction enrolled in PHFS (Penn Heart Failure Study). Assessed were the observational relationship between plasma proteins and (1) all-cause death or (2) death or HF-related hospital admission (DHFA). The authors replicated nominally significant …

The Genetic Basis Of Hydrocephalus: Genes, Pathways, Mechanisms, And Global Impact, Andrew T Hale, Jennifer M Strahle, Et Al.

2020-Current year OA Pubs

Hydrocephalus (HC) is a heterogenous disease characterized by alterations in cerebrospinal fluid (CSF) dynamics that may cause increased intracranial pressure. HC is a component of a wide array of genetic syndromes as well as a secondary consequence of brain injury (intraventricular hemorrhage (IVH), infection, etc.) that can present across the age spectrum, highlighting the phenotypic heterogeneity of the disease. Surgical treatments include ventricular shunting and endoscopic third ventriculostomy with or without choroid plexus cauterization, both of which are prone to failure, and no effective pharmacologic treatments for HC have been developed. Thus, there is an urgent need to understand the …

Reports Of Covid-19 Vaccine Adverse Events In Predominantly Republican Vs Democratic States, David A Asch, Chongliang Luo, Yong Chen

2020-Current year OA Pubs

IMPORTANCE: Antivaccine sentiment is increasingly associated with conservative political positions. Republican-inclined states exhibit lower COVID-19 vaccination rates, but the association between political inclination and reported vaccine adverse events (AEs) is unexplored.

OBJECTIVE: To assess whether there is an association between state political inclination and the reporting rates of COVID-19 vaccine AEs.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used the AE reports after COVID-19 vaccination from the Vaccine Adverse Event Reporting System (VAERS) database from 2020 to 2022, with reports after influenza vaccines from 2019 to 2022 used as a reference. These reports were examined against state-level percentage of Republican …

Inositol Phosphatase Inpp4b Sustains Ilc1s And Intratumoral Nk Cells Through An Akt-Driven Pathway, Vincent Peng, Tihana Trsan, Raki Sudan, Bishan Bhattarai, Victor S Cortez, Martina Molgora, Jean Vacher, Marco Colonna

2020-Current year OA Pubs

Innate lymphoid cells (ILCs) are a heterogeneous population of lymphocytes that coordinate early immune responses and maintain tissue homeostasis. Type 1 innate immune responses are mediated by natural killer (NK) cells and group 1 ILCs (ILC1s). Despite their shared features, NK cells and ILC1s display profound differences among various tissue microenvironments. Here, we identify the inositol polyphosphatase INPP4B as a hallmark feature of tissue-resident ILC1s and intratumoral NK cells using an scRNA-seq atlas of tissue-associated and circulating NK/ILC1s. Conditional deletion of Inpp4b in ILC1s and NK cells reveals that it is necessary for the homeostasis of tissue-resident ILC1s but not …

Survival In Patients With De Novo Metastatic Prostate Cancer, Martin W Schoen, R Bruce Montgomery, Lukas Owens, Saira Khan, Kristen M Sanfilippo, Ruth B Etzioni

2020-Current year OA Pubs

No abstract provided.

Microglia At Sites Of Atrophy Restrict The Progression Of Retinal Degeneration Via Galectin-3 And Trem2, Chen Yu, Yun Chen, Jinchao Hou, Marco Colonna, Et Al.

2020-Current year OA Pubs

Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and niche specialization remain poorly understood, especially in humans. We uncovered a unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and human AMD. In disease models, conditional deletion of galectin-3 in microglia led to phagocytosis defects and consequent augmented photoreceptor death, RPE damage, and vision loss, indicating protective roles. Mechanistically, Trem2 signaling orchestrated microglial migration to atrophic sites and induced galectin-3 …

A Tunable Flat Terahertz Lens Using Dirac Semimetals: A Simulation Study, P Panahianfar, B Rezaei, A Darafsheh

2020-Current year OA Pubs

We propose and design a flat and tunable terahertz lens achieved through a two-dimensional photonic crystal composed of an array of rods made of a Dirac semimetal placed in air as the background medium. The structure of interest is a graded index photonic crystal, made possible by the slight variations in the rods' radii in a direction perpendicular to the direction of the light propagation. Dirac semimetals' ability to respond to variations in their Fermi energy level manifested as a change in the refractive index provides the tunability of our proposed lens. The interaction of electromagnetic waves with the designed …

A Greb1-Steroid Receptor Feedforward Mechanism Governs Differential Greb1 Action In Endometrial Function And Endometriosis, Sangappa B Chadchan, Eryk Andreas, Stephanie J Gunderson, Patricia T Jimenez, Emily S Jungheim, Kelle H Moley, Et Al.

2020-Current year OA Pubs

Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor's transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback …

Gene Dosage Of Independent Dynein Arm Motor Preassembly Factors Influences Cilia Assembly In Chlamydomonas Reinhardtii, Gervette M. Penny, Susan K. Dutcher

2020-Current year OA Pubs

Motile cilia assembly utilizes over 800 structural and cytoplasmic proteins. Variants in approximately 58 genes cause primary ciliary dyskinesia (PCD) in humans, including the dynein arm (pre)assembly factor (DNAAF) gene DNAAF4. In humans, outer dynein arms (ODAs) and inner dynein arms (IDAs) fail to assemble motile cilia when DNAAF4 function is disrupted. In Chlamydomonas reinhardtii, a ciliated unicellular alga, the DNAAF4 ortholog is called PF23. The pf23-1 mutant assembles short cilia and lacks IDAs, but partially retains ODAs. The cilia of a new null allele (pf23-4) completely lack ODAs and IDAs and are even shorter than cilia from pf23-1. In …

On The Psychometric Evaluation Of Cognitive Control Tasks: An Investigation With The Dual Mechanisms Of Cognitive Control (Dmcc) Battery, Jean-Paul Snijder, Rongxiang Tang, Julie M Bugg, Andrew R A Conway, Todd S Braver

2020-Current year OA Pubs

The domain of cognitive control has been a major focus of experimental, neuroscience, and individual differences research. Currently, however, no theory of cognitive control successfully unifies both experimental and individual differences findings. Some perspectives deny that there even exists a unified psychometric cognitive control construct to be measured at all. These shortcomings of the current literature may reflect the fact that current cognitive control paradigms are optimized for the detection of within-subject experimental effects rather than individual differences. In the current study, we examine the psychometric properties of the Dual Mechanisms of Cognitive Control (DMCC) task battery, which was designed …

Extracellular Domain Mutations Of The Egf Receptor Differentially Modulate High-Affinity And Low-Affinity Responses To Egf Receptor Ligands, Jennifer L Macdonald-Obermann, Linda J Pike

2020-Current year OA Pubs

The EGF receptor is mutated in a number of cancers. In most cases, the mutations occur in the intracellular tyrosine kinase domain. However, in glioblastomas, many of the mutations are in the extracellular ligand binding domain. To determine what changes in receptor function are induced by such extracellular domain mutations, we analyzed the binding and biological response to the seven different EGF receptor ligands in three common glioblastoma mutants-R84K, A265V, and G574V. Our data indicate that all three mutations significantly increase the binding affinity of all seven ligands. In addition, the mutations increase the potency of all ligands for stimulating …

Does Vibrotactile Stimulation Of The Auricular Vagus Nerve Enhance Working Memory? A Behavioral And Physiological Investigation, Gansheng Tan, Josh Adams, Kara Donovan, Phillip Demarest, Jon T Willie, Peter Brunner, Jenna L Gorlewicz, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Working memory is essential to a wide range of cognitive functions and activities. Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising method to improve working memory performance. However, the feasibility and scalability of electrical stimulation are constrained by several limitations, such as auricular discomfort and inconsistent electrical contact.

OBJECTIVE: We aimed to develop a novel and practical method, vibrotactile taVNS, to improve working memory. Further, we investigated its effects on arousal, measured by skin conductance and pupil diameter.

METHOD: This study included 20 healthy participants. Behavioral response, skin conductance, and eye tracking data were concurrently recorded while the …

Meniscal Radial Tears: A Classification System Based On Tear Morphology, Jorge Chahla, Derrick M Knapik, Harkirat Jawanda, Felicitas Allende, Horacio Rivarola, Johnathon R Mccormick, Robert F Laprade, Garrett R Jackson

2020-Current year OA Pubs

Appropriate management of radial meniscal tears is complex, with continued efforts focused on optimizing diagnostic methods for identification to help dictate treatment, especially as surgical indications for repair have expanded, coupled with improvements in surgical techniques and instrumentation. Currently, no standardized classification system for radial meniscal tears exists, limiting the ability to accurately characterize injury patterns and guide surgical decision-making.

Efficacy And Safety Of Rezafungin And Caspofungin In Candidaemia And Invasive Candidiasis: Pooled Data From Two Prospective Randomised Controlled Trials, George R Thompson 3rd, Marin Kollef, Et Al.

2020-Current year OA Pubs

BACKGROUND: Rezafungin, a new US Food and Drug Administration-approved, long-acting echinocandin to treat candidaemia and invasive candidiasis, was efficacious with a similar safety profile to caspofungin in clinical trials. We conducted pooled analyses of the phase 2 STRIVE and phase 3 ReSTORE rezafungin trials.

METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial conducted at 66 tertiary care centres in 15 countries. STRIVE was a multicentre, double-blind, double-dummy, randomised phase 2 trial conducted at 44 centres in 10 countries. Adults (≥18 years) with candidaemia or invasive candidiasis were treated with once-a-week intravenous rezafungin (400 mg and 200 mg) …

Multi-View Representation Learning For Tabular Data Integration Using Inter-Feature Relationships, Sandhya Tripathi, Bradley A Fritz, Mohamed Abdelhack, Michael S Avidan, Yixin Chen, Christopher R King

2020-Current year OA Pubs

OBJECTIVE: An applied problem facing all areas of data science is harmonizing data sources. Joining data from multiple origins with unmapped and only partially overlapping features is a prerequisite to developing and testing robust, generalizable algorithms, especially in healthcare. This integrating is usually resolved using meta-data such as feature names, which may be unavailable or ambiguous. Our goal is to design methods that create a mapping between structured tabular datasets derived from electronic health records independent of meta-data.

METHODS: We evaluate methods in the challenging case of numeric features without reliable and distinctive univariate summaries, such as nearly Gaussian and …

Estimating The Treatment And Prophylactic Economic Value Of New Antimicrobials In Managing Antibiotic Resistance And Serious Infections For Common Pathogens In The Usa: A Population Modelling Study, Jason Gordon, Maria Gheorghe, Cale Harrison, Ryan Miller, James Dennis, Lotte Steuten, Simon Goldenberg, Sumanth Gandra, Amer Al-Taie

2020-Current year OA Pubs

BACKGROUND: Antimicrobial resistance is a growing public health concern. There is a global need to estimate the population-level value of developing new antimicrobials and to ensure the effective use of existing antimicrobials as strategies to counteract antimicrobial resistance. To this aim, population-level value criteria need to be considered alongside conventional value measures.

OBJECTIVE: The objective of this study was to develop a novel modelling approach to estimate the value of new antimicrobials, considering the transmission, diversity and enablement elements of STEDI value.

METHODS: We developed a population-based mathematical model for the assessment of antimicrobial value considering both prophylactic use of …

Causal Relationships Between Pain, Medical Treatments, And Knee Osteoarthritis: A Graphical Causal Model To Guide Analyses, Haadiya Cheema, Robert Brophy, Jamie Collins, Charles L Cox, Ali Guermazi, Mahima Kumara, Bruce A Levy, Lindsey Macfarlane, Lisa A Mandl, Robert Marx, Faith Selzer, Kurt Spindler, Jeffrey N Katz, Eleanor J Murray

2020-Current year OA Pubs

OBJECTIVE: Randomized controlled trials (RCTs) are a gold standard for estimating the benefits of clinical interventions, but their decision-making utility can be limited by relatively short follow-up time. Longer-term follow-up of RCT participants is essential to support treatment decisions. However, as time from randomization accrues, loss to follow-up and competing events can introduce biases and require covariate adjustment even for intention-to-treat effects. We describe a process for synthesizing expert knowledge and apply this to long-term follow-up of an RCT of treatments for meniscal tears in patients with knee osteoarthritis (OA).

METHODS: We identified 2 post-randomization events likely to impact accurate …

Technical Note: Minimizing Cied Artifacts On A 0.35 T Mri-Linac Using Deep Learning, Austen N Curcuru, Deshan Yang, Hongyu An, Phillip S Cuculich, Clifford G Robinson, H Michael Gach

2020-Current year OA Pubs

BACKGROUND: Artifacts from implantable cardioverter defibrillators (ICDs) are a challenge to magnetic resonance imaging (MRI)-guided radiotherapy (MRgRT).

PURPOSE: This study tested an unsupervised generative adversarial network to mitigate ICD artifacts in balanced steady-state free precession (bSSFP) cine MRIs and improve image quality and tracking performance for MRgRT.

METHODS: Fourteen healthy volunteers (Group A) were scanned on a 0.35 T MRI-Linac with and without an MR conditional ICD taped to their left pectoral to simulate an implanted ICD. bSSFP MRI data from 12 of the volunteers were used to train a CycleGAN model to reduce ICD artifacts. The data from the …

Impact Of Diagnostic Stewardship Interventions In The Collection Process Of Fungal Blood Cultures, Miguel A Chavez, Satish Munigala, Carey-Ann D Burnham, Melanie L Yarbrough, Crystal Squires, Josephine Fox, Heather Gasama, Kevin Hsueh, David K Warren

2020-Current year OA Pubs

We implemented 2 interventions to improve utilization and contamination at our institution: kits to improve appropriate sample collection and an electronic order alert displaying appropriate indications of fungal blood cultures. An electronic order alert when ordering fungal blood cultures was associated with decreased utilization without decrease in positivity rate.

Hypoimmune Induced Pluripotent Stem Cells Survive Long Term In Fully Immunocompetent, Allogeneic Rhesus Macaques, Xiaomeng Hu, Nathaniel J Hogrebe, Et Al.

2020-Current year OA Pubs

Genetic engineering of allogeneic cell therapeutics that fully prevents rejection by a recipient's immune system would abolish the requirement for immunosuppressive drugs or encapsulation and support large-scale manufacturing of off-the-shelf cell products. Previously, we generated mouse and human hypoimmune pluripotent (HIP) stem cells by depleting HLA class I and II molecules and overexpressing CD47 (B2M

Distributed Feature Representations Of Natural Stimuli Across Parallel Retinal Pathways, Jen-Chun Hsiang, Ning Shen, Florentina Soto, Daniel Kerschensteiner

2020-Current year OA Pubs

How sensory systems extract salient features from natural environments and organize them across neural pathways is unclear. Combining single-cell and population two-photon calcium imaging in mice, we discover that retinal ON bipolar cells (second-order neurons of the visual system) are divided into two blocks of four types. The two blocks distribute temporal and spatial information encoding, respectively. ON bipolar cell axons co-stratify within each block, but separate laminarly between them (upper block: diverse temporal, uniform spatial tuning; lower block: diverse spatial, uniform temporal tuning). ON bipolar cells extract temporal and spatial features similarly from artificial and naturalistic stimuli. In addition, …

The Conceptual Definition Of Sarcopenia: Delphi Consensus From The Global Leadership Initiative In Sarcopenia (Glis), Ben Kirk, Ellen F Binder, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists.

OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia.

DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of …

Genome And Clonal Hematopoiesis Stability Contrasts With Immune, Cfdna, Mitochondrial, And Telomere Length Changes During Short Duration Spaceflight, J Sebastian Garcia-Medina, Irenaeus Chan, Carlos Cruchaga, Kelly Bolton, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure.

METHODS: To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to …

Long-Term Outcomes Of Patients With Large B-Cell Lymphoma Treated With Axicabtagene Ciloleucel And Prophylactic Corticosteroids, Olalekan O Oluwole, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

ZUMA-1 safety management cohort 6 investigated the impact of prophylactic corticosteroids and earlier corticosteroids and/or tocilizumab on the incidence and severity of cytokine release syndrome (CRS) and neurologic events (NEs) following axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). Prior analyses of cohort 6 with limited follow-up demonstrated no Grade ≥3 CRS, a low rate of NEs, and high response rates, without negatively impacting axi-cel pharmacokinetics. Herein, long-term outcomes of cohort 6 (N = 40) are reported (median follow-up, 26.9 months). Since the 1-year analysis (Oluwole, et al. Blood. 2022;138[suppl 1]:2832), no new CRS was reported. …

Biomarker-Directed Targeted Therapy Plus Durvalumab In Advanced Non-Small-Cell Lung Cancer: A Phase 2 Umbrella Trial, Benjamin Besse, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of …

Cystic And Atrophic Kidneys, Atrophic Pancreas, Arcuate Uterus, And Diabetes Mellitus Associated With Deletion Of Hnf1Β Gene, Rachel L Usala, Alberto Sobrero, Amy Riek, Janet Mcgill, Fumihiko Urano

2020-Current year OA Pubs

No abstract provided.

Body Size And Risk Of Colorectal Cancer Molecular Defined Subtypes And Pathways: Mendelian Randomization Analyses, Nikos Papadimitriou, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain.

METHODS: We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO).

FINDINGS: A 1-standard deviation (SD:5.1 kg/m

INTERPRETATION: Body size was more strongly …