Digital Commons Network^™

Multi-Omics Investigation Of Clostridioides Difficile-Colonized Patients Reveals Pathogen And Commensal Correlates Of C. Difficile Pathogenesis, Skye R.S. Fishbein, John I. Robinson, Tiffany Hink, Kimberly A. Reske, Erin P. Newcomer, Carey-Ann D. Burnham, Jeffrey P. Henderson, Erik R. Dubberke, Gautam Dantas

Open Access Publications

No abstract provided.

An Evidence-Based Definition Of Anemia For Singleton, Uncomplicated Pregnancies, Amanda C. Zofkie, W. Holt Garner, Rachel C. Schell, Alexandra S. Ragsdale, Donald D. Mcintire, Scott W. Roberts, Catherine Y. Spong

Open Access Publications

BACKGROUND: The definition for anemia in pregnancy is outdated, derived from Scandinavian studies in the 1970's to 1980's. To identity women at risk of blood transfusion, a common cause of Severe Maternal Morbidity, a standard definition of anemia in pregnancy in a modern, healthy United States cohort is needed.

OBJECTIVE: To define anemia in pregnancy in a United States population including a large county vs. private hospital population using uncomplicated patients.

MATERIALS AND METHODS: Inclusion criteria were healthy women with the first prenatal visit before 20 weeks. Exclusion criteria included preterm birth, preeclampsia, hypertension, diabetes, short interval pregnancy (<18 months), multiple gestation, abruption, and fetal demise. All women had iron fortification (Ferrous sulfate 325 mg daily) recommended. The presentation to care and pre-delivery hematocrits were obtained, and the percentiles determined. A total of 2000 patients were included, 1000 from the public county hospital and 1000 from the private hospital. Each cohort had 250 patients in each 2011, 2013, 2015, and 2018. The cohorts were compared for differences in the fifth percentile for each antepartum epoch. Student's t-test and chi-squared statistical tests were used for analysis, p-value of ≤0.05 was considered significant.

RESULTS: …

Fish In The Sea: Number, Characteristics, And Partner Preferences Of Unmarried Japanese Adults - Analysis Of A National Survey, Cyrus Ghaznavi, Haruka Sakamoto, Shuhei Nomura, Anna Kubota, Daisuke Yoneoka, Kenji Shibuya, Peter Ueda

Open Access Publications

BACKGROUND: A large proportion of adults in Japan remain unmarried even though they intend to marry during their lifetime. To provide data for policy makers and those searching for partners in the Japanese marriage market, we estimated the number and characteristics of unmarried women and men with marriage intention and assessed their partner preferences. Based on the findings, we hypothesized regarding potential mismatches between the individuals available in the marriage market and the type of partners they are looking for.

METHODS: We used data from the National Fertility Survey (2015), a nationally representative survey in Japan, and included 20,344 participants …

High Temporal Resolution Measurements Of Movement Reveal Novel Early-Life Physiological Decline In C. Elegans, Drew Benjamin Sinha, Zachary Scott Pincus

Open Access Publications

Age-related physiological changes are most notable and best-studied late in life, while the nature of aging in early- or middle-aged individuals has not been explored as thoroughly. In C. elegans, many studies of movement vs. age generally focus on three distinct phases: sustained, youthful movement; onset of rapidly progressing impairment; and gross immobility. We investigated whether this first period of early-life adult movement is a sustained "healthy" level of high function followed by a discrete "movement catastrophe"-or whether there are early-life changes in movement that precede future physiological declines. To determine how movement varies during early adult life, we followed …

Estimated Population Access To Acute Stroke And Telestroke Centers In The Us, 2019, Kori S. Zachrison, Rebecca E. Cash, Opeolu Adeoye, Krislyn M. Boggs, Lee H. Schwamm, Ateev Mehrotra, Carlos A. Camargo

Open Access Publications

No abstract provided.

Advances And Gaps In Sars-Cov-2 Infection Models, César Muñoz-Fontela, Michael S. Diamond, Et Al

Open Access Publications

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to …

Gastric Organoids: Progress And Remaining Challenges, Min-Jiao Pang, Joseph R Burclaff, Ramon Jin, Mahliyah Adkins-Threats, Luciana H Osaki, Yunan Han, Jason C Mills, Zhi-Feng Miao, Zhen-Ning Wang

Open Access Publications

The stomach is a complex and physiologically necessary organ, yet large differences in physiology between mouse and human stomachs have impeded translation of physiological discoveries and drug screens performed using murine gastric tissues. Gastric cancer (GC) is a global health threat, with a high mortality rate and limited treatment options. The heterogeneous nature of GC makes it poorly suited for current "one size fits all" standard treatments. In this review, we discuss the rapidly evolving field of gastric organoids, with a focus on studies expanding cultures from primary human tissues and describing the benefits of mouse organoid models. We introduce …

Disruption Of Thymic Central Tolerance By Infection With Murine Roseolovirus Induces Autoimmune Gastritis, Tarin M. Bigley, Liping Yang, Liang-I Kang, Jose B. Saenz, Francisco Victorino, Wayne M. Yokoyama

Open Access Publications

Infections with herpesviruses, including human roseoloviruses, have been proposed to cause autoimmune disease, but defining a causal relationship and mechanism has been difficult due to the ubiquitous nature of infection and development of autoimmunity long after acute infection. Murine roseolovirus (MRV) is highly related to human roseoloviruses. Herein we show that neonatal MRV infection induced autoimmune gastritis (AIG) in adult mice in the absence of ongoing infection. MRV-induced AIG was dependent on replication during the neonatal period and was CD4+ T cell and IL-17 dependent. Moreover, neonatal MRV infection was associated with development of a wide array of autoantibodies in …

Sonobiopsy For Minimally Invasive, Spatiotemporally-Controlled, And Sensitive Detection Of Glioblastoma-Derived Circulating Tumor Dna, Christopher Pacia, Jinyun Yuan, Yimei Yue, Lu Xu, Arash Nazeri, Rupen Desai, H. Michael Gach, Xiaowei Wang, Michael Talcott, Aadel Chaudhuri, Gavin Dunn, Eric Leuthardt, Hong Chen

Open Access Publications

No abstract provided.

Neutrophil Dream Promotes Neutrophil Recruitment In Vascular Inflammation, Jing Li, Tripti Kumari, Andrew Barazia, Vishwanath Jha, Si-Yeon Jeong, Amber Olson, Mijeong Kim, Bum-Kyu Lee, Vijayprakash Manickam, Zhimin Song, Regina Clemens, Babak Razani, Jonghwan Kim, Mary C Dinauer, Jaehyung Cho

Open Access Publications

The interaction between neutrophils and endothelial cells is critical for the pathogenesis of vascular inflammation. However, the regulation of neutrophil adhesive function remains not fully understood. Intravital microscopy demonstrates that neutrophil DREAM promotes neutrophil recruitment to sites of inflammation induced by TNF-α but not MIP-2 or fMLP. We observe that neutrophil DREAM represses expression of A20, a negative regulator of NF-κB activity, and enhances expression of pro-inflammatory molecules and phosphorylation of IκB kinase (IKK) after TNF-α stimulation. Studies using genetic and pharmacologic approaches reveal that DREAM deficiency and IKKβ inhibition significantly diminish the ligand-binding activity of β2 integrins in TNF-α-stimulated …

Clinical And Kidney Structural Characteristics Of Living Kidney Donors With Nephrolithiasis And Their Long-Term Outcomes, Matthew R D'Costa, Massini A Merzkani, Aleksandar Denic, Aidan F Mullan, Joseph J Larson, Walter K Kremers, Walter D Park, Mariam P Alexander, Harini A Chakkera, Sandra J Taler, Stephen J Erickson, Mark D Stegall, Naim Issa, Andrew D Rule

Open Access Publications

Background: Nephrolithiasis in living kidney donors is concerning due to the potential impact on long-term postdonation kidney function.

Methods: We performed a cohort study of living kidney donors from 2 centers with a baseline computed tomography scan and implantation renal biopsy. Donors (>5 y since donation) completed a follow-up survey or underwent chart review to assess eGFR and incident hypertension. Stone formers were classified as symptomatic if they had a past symptomatic episode or asymptomatic if only incidental radiographic kidney stones were identified during donor evaluation. We compared baseline clinical, imaging, and biopsy characteristics by stone former status including …

Epigenetic Regulation Of Human T‐Cell Leukemia Virus Gene Expression, Lee Ratner

Open Access Publications

No abstract provided.

Dopamine D4 Receptor Is A Regulator Of Morphine-Induced Plasticity In The Rat Dorsal Striatum, Alicia Rivera, Diana Suarez-Boomgard, Cristina Miguelez, Alejandra Valderrama-Carvajal, Jerome Baufreton, Kirill Shumilov, Anne Taupignon, Belen Gago, M.Angeles Real

Open Access Publications

No abstract provided.

Utility Of Using Electrocardiogram Measures Of Heart Rate Variability As A Measure Of Cardiovascular Autonomic Neuropathy In Type 1 Diabetes Patients, Rodica Pop-Busui, Jye-Yu C Backlund, Ionut Bebu, Barbara H Braffett, Gayle Lorenzi, Neil H White, John M Lachin, Elsayed Z Soliman, Dcct/Edic Research Group

Open Access Publications

AIMS/INTRODUCTION: Cardiovascular autonomic neuropathy (CAN) is a predictor of cardiovascular disease and mortality. Cardiovascular reflex tests (CARTs) are the gold standard for the diagnosis of CAN, but might not be feasible in large research cohorts or in clinical care. We investigated whether measures of heart rate variability obtained from standard electrocardiogram (ECG) recordings provide a reliable measure of CAN.

MATERIALS AND METHODS: Standardized CARTs (R-R response to paced breathing, Valsalva, postural changes) and digitized 12-lead resting ECGs were obtained concomitantly in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications participants (n = 311). Standard deviation of normally conducted …

Differences In Shoulder Internal Rotation Strength Between Baseball Players With Ulnar Collateral Ligament Reconstruction And Healthy Controls, Sean Kennedy, Philip Sheedy, Brooks Klein, Mason Gist, Joseph Hannon, John Conway, Kalyssa Creed, J. Craig Garrison

Open Access Publications

Background: Studies have indicated decreased shoulder internal rotation (IR) and external rotation (ER) strength in the throwing limb of baseball players after ulnar collateral ligament injury. There is limited evidence on the recovery of shoulder rotation strength after primary ulnar collateral ligament reconstruction (UCLR).

Hypothesis: At the time of return to throwing, baseball players who underwent UCLR would demonstrate decreased IR and ER shoulder strength in the throwing arm as compared with healthy baseball players.

Study Design: Cross-sectional study; Level of evidence, 3.

Methods: Male competitive high school and collegiate baseball athletes participated in this study. Athletes who underwent UCLR …

Task Modulation Of Single-Neuron Activity In The Human Amygdala And Hippocampus, Runnan Cao, Alexander Todorov, Nicholas Brandmeir, Shuo Wang

Open Access Publications

The human amygdala and hippocampus are critically involved in various processes in face perception. However, it remains unclear how task demands or evaluative contexts modulate processes underlying face perception. In this study, we employed two task instructions when participants viewed the same faces and recorded single-neuron activity from the human amygdala and hippocampus. We comprehensively analyzed task modulation for three key aspects of face processing and we found that neurons in the amygdala and hippocampus (1) encoded high-level social traits such as perceived facial trustworthiness and dominance and this response was modulated by task instructions; (2) encoded low-level facial features …

Mitigating The Effects Of Covid-19 On Hiv Treatment And Care In Lusaka, Zambia: A Before-After Cohort Study Using Mixed Effects Regression, Jake Pry, Kombatende Sikombe, Aaloke Mody, Shilpa Iyer, Jacob Mutale, Natalie Vlahakis, Theodora Savory, Mwanza Wa Mwanza, Keith Mweebo, Annie Mwila, Consity Mwale, Mpande Mukumbwa-Mwenechanya, Andrew Kerkhoff, Izukanji Sikazwe, Carolyn Bolton Moore, Daniel Mwamba, Elvin Geng, Michael Herce

Open Access Publications

INTRODUCTION: The Zambian Ministry of Health (MoH) issued COVID-19 mitigation guidance for HIV care immediately after the first COVID-19 case was confirmed in Zambia on 18 March 2020. The Centre for Infectious Disease Research in Zambia implemented MoH guidance by: 1) extending antiretroviral therapy (ART) refill duration to 6 multi-month dispensation (6MMD) and 2) task-shifting communication and mobilisation of those in HIV care to collect their next ART refill early. We assessed the impact of COVID-19 mitigation guidance on HIV care 3 months before and after guidance implementation.

METHODS: We reviewed all ART pharmacy visit data in the national HIV …

Severe Ocrelizumab-Induced Enterocolitis Treated Successfully With Ustekinumab, Janaki Shah, Ahmad Al-Taaee, Parakkal Deepak, Anas Gremida

Open Access Publications

No abstract provided.

M6a Modifications Regulate Intestinal Immunity And Rotavirus Infection, Anmin Wang, Gaopeng Hou, Siyuan Ding, Et Al

Open Access Publications

N6-methyladenosine (m6A) is an abundant mRNA modification and affects many biological processes. However, how m6A levels are regulated during physiological or pathological processes such as virus infections, and the in vivo function of m6A in the intestinal immune defense against virus infections are largely unknown. Here, we uncover a novel antiviral function of m6A modification during rotavirus (RV) infection in small bowel intestinal epithelial cells (IECs). We found that rotavirus infection induced global m6A modifications on mRNA transcripts by down-regulating the m6a eraser ALKBH5. Mice lacking the m6A writer enzymes METTL3 in IECs (

The Mutationathon Highlights The Importance Of Reaching Standardization In Estimates Of Pedigree-Based Germline Mutation Rates, Lucie A. Bergeron, Tychele Turner, Et Al

Open Access Publications

In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various nonhuman species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and appropriately accounting for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a 'Mutationathon,' a …

Perceptions Of Risk Of Sars-Cov-2 Transmission In Social And Educational Activities By Infectious Diseases And General Pediatric Healthcare Providers, A Pre-Vaccine Risk Perception Cross-Sectional Survey, Andrew B. Janowski, Philip M. Polgreen, Susan E. Beekmann, Jason G. Newland

Open Access Publications

BACKGROUND: The perception of the transmission risks of SARS-CoV-2 in social and educational settings by US healthcare providers have not been previously quantified.

METHODS: Respondents completed an online survey between September and October 2020 to estimate the risk of SARS-CoV-2 transmission on a scale of 0-10 for different social and educational activities prior to the availability of the SARS-CoV-2 vaccines. Demographic information and experiences during the pandemic were also collected. The risk assessment was emailed to three listservs of healthcare providers, including national listservs of pediatric (PID) and adult infectious diseases (AID) providers, and a listserv of general pediatric practitioners …

Ultrasound-Guided Thrombin Injection For The Treatment Of Bleeding Following Kidney And Liver Biopsies, Mark J Hoegger, William D Middleton

Open Access Publications

The purpose of this study was to describe the technique and outcomes of percutaneous thrombin injection into the superficial aspect of actively bleeding liver and kidney biopsy tracks identified with color Doppler ultrasound with the aim of hemorrhage termination. After percutaneous thrombin injection, 15/16 (94%) patients did not require further intervention. Ultrasound-guided thrombin injection into the superficial site of active bleeding is an effective technique for terminating bleeding in the immediate post-procedure period following kidney and liver biopsies and should be considered if active bleeding persists on color Doppler after ≥30 minutes of compression and observation.

Augmented Cardiac Growth Hormone Signaling Contributes To Cardiomyopathy Following Genetic Disruption Of The Cardiomyocyte Circadian Clock, Ravi Sonkar, Ryan Berry, Mary N Latimer, Sumanth D Prabhu, Martin E Young, Stuart J Frank

Open Access Publications

Circadian clocks regulate numerous biological processes, at whole body, organ, and cellular levels. This includes both hormone secretion and target tissue sensitivity. Although growth hormone (GH) secretion is time-of-day-dependent (increased pulse amplitude during the sleep period), little is known regarding whether circadian clocks modulate GH sensitivity in target tissues. GH acts in part through induction of insulin-like growth factor 1 (IGF1), and excess GH/IGF1 signaling has been linked to pathologies such as insulin resistance, acromegaly, and cardiomyopathy. Interestingly, genetic disruption of the cardiomyocyte circadian clock leads to cardiac adverse remodeling, contractile dysfunction, and reduced lifespan. These observations led to the …

Ethical, Regulatory, And Practical Barriers To Covid-19 Research: A Stakeholder-Informed Inventory Of Concerns, Bryan A. Sisk, Kari Baldwin, Meredith Parsons, James M. Dubois

Open Access Publications

INTRODUCTION: SARS-CoV-2 (COVID-19) has caused death and economic injury around the globe. The urgent need for COVID-19 research created new ethical, regulatory, and practical challenges. The next public health emergency could be worse than COVID-19. We must learn about these challenges from the experiences of researchers and Research Ethics Committee professionals responsible for these COVID-19 studies to prepare for the next emergency.

MATERIALS AND METHODS: We conducted an online survey to identify the ethical, oversight, and regulatory challenges of conducting COVID-19 research during the early pandemic, and proposed solutions for overcoming these barriers. Using criterion-based, convenience sampling, we invited researchers …

Hemodynamic Profiles By Non-Invasive Monitoring Of Cardiac Index And Vascular Tone In Acute Heart Failure Patients In The Emergency Department: External Validation And Clinical Outcomes, Nicholas Eric Harrison, Sarah Meram, Xiangrui Li, Morgan B. White, Sarah Henry, Sushane Gupta, Dongxiao Zhu, Peter Pang, Phillip Levy

Open Access Publications

BACKGROUND: Non-invasive finger-cuff monitors measuring cardiac index and vascular tone (SVRI) classify emergency department (ED) patients with acute heart failure (AHF) into three otherwise-indistinguishable subgroups. Our goals were to validate these "hemodynamic profiles" in an external cohort and assess their association with clinical outcomes.

METHODS: AHF patients (n = 257) from five EDs were prospectively enrolled in the validation cohort (VC). Cardiac index and SVRI were measured with a ClearSight finger-cuff monitor (formerly NexFin, Edwards Lifesciences) as in a previous study (derivation cohort, DC, n = 127). A control cohort (CC, n = 127) of ED patients with sepsis was …

Association Of A Perioperative Multicomponent Fall Prevention Intervention With Falls And Quality Of Life After Elective Inpatient Surgical Procedures, Bradley A. Fritz, Christopher R. King, Divya Mehta, Emily Somerville, Alex Kronzer, Arbi Ben Abdallah, Troy Wildes, Michael S. Avidan, Eric J. Lenze, Susan Stark

Open Access Publications

Importance: Falls after elective inpatient surgical procedures are common and have physical, emotional, and financial consequences. Close interactions between patients and health care teams before and after surgical procedures may offer opportunities to address modifiable risk factors associated with falls.

Objective: To assess whether a multicomponent intervention that incorporates education, home medication review, and home safety assessment is associated with reductions in the incidence of falls after elective inpatient surgical procedures.

Design, Setting, and Participants: This prospective propensity score-matched cohort study was a prespecified secondary analysis of data from the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized …

Association Of Multidimensional Poverty With Dementia In Adults Aged 50 Years Or Older In South Africa, Jean-Francois Trani, Jacqueline Moodley, May Thu Thu Maw, Ganesh M. Babulal

Open Access Publications

Importance: Limited research exists investigating the association between multidimensional poverty and dementia in low-and middle-income countries (LMICs).

Objective: To investigate the association between multidimensional poverty and dementia among adults aged 50 years or older living in South Africa.

Design, Setting, and Participants: This cross-sectional study was conducted in Soweto, Johannesburg, South Africa, between November 11, 2019, and February 28, 2020. Participants included 227 adults aged 50 years or older. Data analysis was concluded from August 1 to 30, 2021.

Exposures: Multidimensional poverty included 7 dimensions that are central to well-being (education, health, economic activity, living standards, social participation, fair treatment, …

De Novo Missense Variants In Fbxo11 Alter Its Protein Expression And Subcellular Localization, Anne Gregor, Marwan Shinawi, Et Al

Open Access Publications

Recently, others and we identified de novo FBXO11 (F-Box only protein 11) variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant …

Nia Long Life Family Study: Objectives, Design, And Heritability Of Cross-Sectional And Longitudinal Phenotypes, Mary K. Wojczynski, Shiow Jiuan Lin, Paola Sebastiani, Thomas T. Perls, Joseph Lee, Alexander Kulminski, Anne Newman, Joe M. Zmuda, Kaare Christensen, Michael A. Province

Open Access Publications

The NIA Long Life Family Study (LLFS) is a longitudinal, multicenter, multinational, population-based multigenerational family study of the genetic and nongenetic determinants of exceptional longevity and healthy aging. The Visit 1 in-person evaluation (2006-2009) recruited 4 953 individuals from 539 two-generation families, selected from the upper 1% tail of the Family Longevity Selection Score (FLoSS, which quantifies the degree of familial clustering of longevity). Demographic, anthropometric, cognitive, activities of daily living, ankle-brachial index, blood pressure, physical performance, and pulmonary function, along with serum, plasma, lymphocytes, red cells, and DNA, were collected. A Genome Wide Association Scan (GWAS) (Ilumina Omni 2.5M …

Fracture Healing Is Delayed In The Absence Of Gasdermin-Interleukin-1 Signaling, Kai Sun, Chun Wang, Jianqiu Xiao, Michael D. Brodt, Luorongxin Yuan, Tong Yang, Yael Alippe, Huimin Hu, Dingjun Hao, Yousef Abu-Amer, Matthew J. Silva, Jie Shen, Gabriel Mbalaviele

Open Access Publications

Amino-terminal fragments from proteolytically cleaved gasdermins (GSDMs) form plasma membrane pores that enable the secretion of interleukin-1β (IL-1β) and IL-18. Excessive GSDM-mediated pore formation can compromise the integrity of the plasma membrane thereby causing the lytic inflammatory cell death, pyroptosis. We found that GSDMD and GSDME were the only GSDMs that were readily expressed in bone microenvironment. Therefore, we tested the hypothesis that GSDMD and GSDME are implicated in fracture healing owing to their role in the obligatory inflammatory response following injury. We found that bone callus volume and biomechanical properties of injured bones were significantly reduced in mice lacking …