Digital Commons Network^™

Effect Of Enhanced Medical Rehabilitation On Functional Recovery In Older Adults Receiving Skilled Nursing Care After Acute Rehabilitation: A Randomized Clinical Trial, Eric J. Lenze, Emily Lenard, Marghuretta Bland, Peggy Barco, J Philip Miller, Michael Yingling, Catherine E. Lang, Nancy Morrow-Howell, Carolyn M. Baum, Ellen F. Binder, Thomas L. Rodebaugh

Open Access Publications

Importance: Enhanced medical rehabilitation (EMR) is a systematic and standardized approach for physical and occupational therapists to engage patients. Higher patient engagement in therapy might lead to improved functional recovery in rehabilitation settings, such as skilled nursing facilities (SNFs).

Objective: To determine whether EMR improves older adults' functional recovery.

Design, Setting, and Participants: A double-blind, parallel-group, randomized clinical trial was conducted from July 29, 2014, to July 13, 2018, in 229 adults aged 65 years or older admitted to 2 US SNFs. Participants were randomized to receive EMR (n = 114) vs standard-of-care rehabilitation (n = 115). Intention-to-treat analysis was …

Trends In Medical Imaging During Pregnancy In The United States And Ontario, Canada, 1996 To 2016, Marilyn L. Kwan, James R. Duncan, Et Al

Open Access Publications

No abstract provided.

A Guinea Fowl Genome Assembly Provides New Evidence On Evolution Following Domestication And Selection In Galliformes, Alain Vignal, Simon Boitard, Noémie Thébault, Guiguigbaza-Kossigan Dayo, Valentine Yapi-Gnaore, Issaka Youssao Abdou Karim, Cécile Berthouly-Salazar, Nóra Pálinkás-Bodzsár, Daniel Guémené, Francoise Thibaud-Nissen, Wesley C Warren, Michèle Tixier-Boichard, Xavier Rognon

Open Access Publications

The helmeted guinea fowl Numida meleagris belongs to the order Galliformes. Its natural range includes a large part of sub-Saharan Africa, from Senegal to Eritrea and from Chad to South Africa. Archaeozoological and artistic evidence suggest domestication of this species may have occurred about 2,000 years BP in Mali and Sudan primarily as a food resource, although villagers also benefit from its capacity to give loud alarm calls in case of danger, of its ability to consume parasites such as ticks and to hunt snakes, thus suggesting its domestication may have resulted from a commensal association process. Today, it is …

The Future Is Open: Open-Source Tools For Behavioral Neuroscience Research, Samantha R White, Linda M Amarante, Alexxai V Kravitz, Mark Laubach

Open Access Publications

No abstract provided.

Disseminating And Implementing A Lifestyle-Based Healthy Weight Program For Mothers In A National Organization: A Study Protocol For A Cluster Randomized Trial, Rachel G Tabak, Cynthia D Schwarz, Allison Kemner, Kenneth B Schechtman, Karen Steger-May, Veronda Byrth, Debra Haire-Joshu

Open Access Publications

BACKGROUND: Excessive weight gain among young adult women age 18-45 years is an alarming and overlooked trend that must be addressed to reverse the epidemics of obesity and chronic disease. During this vulnerable period, women tend to gain disproportionally large amounts of weight compared to men and to other life periods. Healthy Eating and Active Living Taught at Home (HEALTH) is a lifestyle modification intervention developed in partnership with Parents as Teachers (PAT), a national home visiting, community-based organization with significant reach in this population. HEALTH prevented weight gain, promoted sustained weight loss, and reduced waist circumference. PAT provides parent-child …

Unified Single-Cell Analysis Of Testis Gene Regulation And Pathology In Five Mouse Strains, Min Jung, Daniel Wells, Jannette Rusch, Suhaira Ahmad, Jonathan Marchini, Simon R. Myers, Donald F. Conrad

Open Access Publications

To fully exploit the potential of single-cell functional genomics in the study of development and disease, robust methods are needed to simplify the analysis of data across samples, time-points and individuals. Here we introduce a model-based factor analysis method, SDA, to analyze a novel 57,600 cell dataset from the testes of wild-type mice and mice with gonadal defects due to disruption of the genes

Training In Implementation Practice Leadership (Triple): Evaluation Of A Novel Practice Change Strategy In Behavioral Health Organizations, Enola Proctor, Alex T Ramsey, Matthew T Brown, Sara Malone, Cole Hooley, Virginia Mckay

Open Access Publications

BACKGROUND: Effective leadership for organizational change is critical to the implementation of evidence-based practices (EBPs). As organizational leaders in behavioral health organizations often are promoted from within the agency for their long-standing, effective work as counselors, they may lack formal training in leadership, management, or practice change. This study assesses a novel implementation leadership training designed to promote leadership skills and successful organizational change specific to EBP implementation.

METHODS: We conducted a pre-post outcome evaluation of the Training in Implementation Practice Leadership (TRIPLE), delivered via three in-person, half-day training sessions, with interim coaching and technical support. Sixteen mid-level leaders (75% …

Intracellular Retention Of Mutant Lysyl Oxidase Leads To Aortic Dilation In Response To Increased Hemodynamic Stress, Vivian S Lee, Carmen M Halabi, Thomas J Broekelmann, Philip C Trackman, Nathan O Stitziel, Robert P Mecham

Open Access Publications

Heterozygous missense mutations in lysyl oxidase (LOX) are associated with thoracic aortic aneurysms and dissections. To assess how LOX mutations modify protein function and lead to aortic disease, we studied the factors that influence the onset and progression of vascular aneurysms in mice bearing a Lox mutation (p.M292R) linked to aortic dilation in humans. We show that mice heterozygous for the M292R mutation did not develop aneurysmal disease unless challenged with increased hemodynamic stress. Vessel dilation was confined to the ascending aorta although both the ascending and descending aortae showed changes in vessel wall structure, smooth muscle cell number and …

Vesicular Glutamatergic Transmission In Noise-Induced Loss And Repair Of Cochlear Ribbon Synapses, Kyunghee X. Kim, Shelby Payne, Aizhen Yang-Hood, Song-Zhe Li, Bethany Davis, Jason Carlquist, Babak V-Ghaffari, Jay A. Gantz, Dorina Kallogjeri, James A.J. Fitzpatrick, Kevin K. Ohlemiller, Keiko Hirose, Mark A. Rutherford

Open Access Publications

Noise-induced excitotoxicity is thought to depend on glutamate. However, the excitotoxic mechanisms are unknown, and the necessity of glutamate for synapse loss or regeneration is unclear. Despite absence of glutamatergic transmission from cochlear inner hair cells in mice lacking the vesicular glutamate transporter-3 (

Phase Ii Trial Of Levocetirizine With Capecitabine And Bevacizumab To Overcome The Resistance Of Antiangiogenic Therapies In Refractory Metastatic Colorectal Cancer, Manik Amin, Monica Desai, Kathryn Trinkaus, Amberly Brown, Andrea Wang-Gillam, Benjamin Tan, Joel Picus, Steven Sorscher, Maureen Highkin, Kim Lears, Albert C. Lockhart

Open Access Publications

Background: Despite the clinical success of vascular endothelial growth factor (VEGF) blockade in metastatic colorectal cancers (mCRC), resistance to anti-angiogenic drugs invariably develops. IL-8 and other cytokines have been implicated in development of resistance to anti-angiogenic therapy. Levocetirizine is a second generation H1 antihistamine with anti-inflammatory and IL-8 suppression properties. We conducted a phase II trial combining levocetirizine with capecitabine and bevacizumab to potentially overcome anti-angiogenic therapy resistance in patients with refractory mCRC.

Methods: This was a single-center open-label prospective trial in refractory mCRC patients. Treatment consisted of oral capecitabine 850 mg/m

Results: Forty-seven patients were enrolled in the trial …

The Constances Job Exposure Matrix Based On Self-Reported Exposure To Physical Risk Factors: Development And Evaluation, Bradley A Evanoff, Marcus Yung, Skye Buckner-Petty, Johan Hviid Andersen, Yves Roquelaure, Alexis Descatha, Ann Marie Dale

Open Access Publications

OBJECTIVES: Job exposure matrices (JEMs) can be constructed from expert-rated assessments, direct measurement and self-reports. This paper describes the construction of a general population JEM based on self-reported physical exposures, its ability to create homogeneous exposure groups (HEG) and the use of different exposure metrics to express job-level estimates.

METHODS: The JEM was constructed from physical exposure data obtained from the Cohorte des consultants des Centres d'examens de santé (CONSTANCES). Using data from 35 526 eligible participants, the JEM consisted of 27 physical risk factors from 407 job codes. We determined whether the JEM created HEG by performing non-parametric multivariate …

Apolipoprotein E Associated With Reconstituted High-Density Lipoprotein-Like Particles Is Protected From Aggregation., Ellen Hubin, Philip B Verghese, Nico Van Nuland, Kerensa Broersen

Open Access Publications

Apolipoprotein E (APOE) genotype determines Alzheimer's disease (AD) susceptibility, with the APOE ε4 allele being an established risk factor for late-onset AD. The ApoE lipidation status has been reported to impact amyloid-beta (Aβ) peptide metabolism. The details of how lipidation affects ApoE behavior remain to be elucidated. In this study, we prepared lipid-free and lipid-bound ApoE particles, mimicking the high-density lipoprotein particles found in vivo, for all three isoforms (ApoE2, ApoE3, and ApoE4) and biophysically characterized them. We find that lipid-free ApoE in solution has the tendency to aggregate in vitro in an isoform-dependent manner under near-physiological conditions and that …

Ddr2 Controls Breast Tumor Stiffness And Metastasis By Regulating Integrin Mediated Mechanotransduction In Cafs, Samantha V.H. Bayer, Whitney R. Grither, Audrey Brenot, Priscilla Y. Hwang, Craig E. Barcus, Melanie Ernst, Patrick Pence, Christopher Walter, Amit Pathak, Gregory D. Longmore

Open Access Publications

Biomechanical changes in the tumor microenvironment influence tumor progression and metastases. Collagen content and fiber organization within the tumor stroma are major contributors to biomechanical changes (e., tumor stiffness) and correlated with tumor aggressiveness and outcome. What signals and in what cells control collagen organization within the tumors, and how, is not fully understood. We show in mouse breast tumors that the action of the collagen receptor DDR2 in CAFs controls tumor stiffness by reorganizing collagen fibers specifically at the tumor-stromal boundary. These changes were associated with lung metastases. The action of DDR2 in mouse and human CAFs, and tumors …

The Subjective Value Of Cognitive Effort Is Encoded By A Domain-General Valuation Network, Andrew Westbrook, Bidhan Lamichhane, Todd Braver

Open Access Publications

Cognitive control is necessary for goal-directed behavior, yet people treat cognitive control demand as a cost, which discounts the value of rewards in a similar manner as other costs, such as delay or risk. It is unclear, however, whether the subjective value (SV) of cognitive effort is encoded in the same putatively domain-general brain valuation network implicated in other cost domains, or instead engages a distinct frontoparietal network, as implied by recent studies. Here, we provide rigorous evidence that the valuation network, with core foci in the ventromedial prefrontal cortex and ventral striatum, also encodes SV during cognitive effort-based decision-making …

Celltag Indexing: Genetic Barcode-Based Sample Multiplexing For Single-Cell Genomics, Chuner Guo, Wenjun Kong, Kenji Kamimoto, Guillermo C Rivera-Gonzalez, Xue Yang, Yuhei Kirita, Samantha A Morris

Open Access Publications

High-throughput single-cell assays increasingly require special consideration in experimental design, sample multiplexing, batch effect removal, and data interpretation. Here, we describe a lentiviral barcode-based multiplexing approach, CellTag Indexing, which uses predefined genetic barcodes that are heritable, enabling cell populations to be tagged, pooled, and tracked over time in the same experimental replicate. We demonstrate the utility of CellTag Indexing by sequencing transcriptomes using a variety of cell types, including long-term tracking of cell engraftment and differentiation in vivo. Together, this presents CellTag Indexing as a broadly applicable genetic multiplexing tool that is complementary with existing single-cell technologies.

Cns Myelination And Remyelination Depend On Fatty Acid Synthesis By Oligodendrocytes, Penelope Dimas, Laura Montani, Jorge A. Pereira, Daniel Moreno, Martin Trötzmüller, Joanne Gerber, Clay F. Semenkovich, Harald C. Köfeler, Ueli Suter

Open Access Publications

Oligodendrocytes (OLs) support neurons and signal transmission in the central nervous system (CNS) by enwrapping axons with myelin, a lipid-rich membrane structure. We addressed the significance of fatty acid (FA) synthesis in OLs by depleting FA synthase (FASN) from OL progenitor cells (OPCs) in transgenic mice. While we detected no effects in proliferation and differentiation along the postnatal OL lineage, we found that FASN is essential for accurate myelination, including myelin growth. Increasing dietary lipid intake could partially compensate for the FASN deficiency. Furthermore, FASN contributes to correct myelin lipid composition and stability of myelinated axons. Moreover, we depleted FASN …

Regulation Of Cilia Abundance In Multiciliated Cells, Rashmi Nanjundappa, Dong Kong, Kyuhwan Shim, Tim Stearns, Steven L. Brody, Jadranka Loncarek, Moe R. Mahjoub

Open Access Publications

Multiciliated cells (MCC) contain hundreds of motile cilia used to propel fluid over their surface. To template these cilia, each MCC produces between 100-600 centrioles by a process termed centriole amplification. Yet, how MCC regulate the precise number of centrioles and cilia remains unknown. Airway progenitor cells contain two parental centrioles (PC) and form structures called deuterosomes that nucleate centrioles during amplification. Using an ex vivo airway culture model, we show that ablation of PC does not perturb deuterosome formation and centriole amplification. In contrast, loss of PC caused an increase in deuterosome and centriole abundance, highlighting the presence of …

Mutant Huntingtin Enhances Activation Of Dendritic Kv4 K+ Channels In Striatal Spiny Projection Neurons, Luis Carrillo-Reid, Michelle Day, Zhong Xie, Alexandria E. Melendez, Jyothisri Kondapalli, Joshua L. Plotkin, David L. Wokosin, Yu Chen, Geraldine J. Kress, Michael Kaplitt, Ema Ilijic, Jaime N. Guzman, C Savio Chan, D James Surmeier

Open Access Publications

Huntington's disease (HD) is initially characterized by an inability to suppress unwanted movements, a deficit attributable to impaired synaptic activation of striatal indirect pathway spiny projection neurons (iSPNs). To better understand the mechanisms underlying this deficit, striatal neurons in ex vivo brain slices from mouse genetic models of HD were studied using electrophysiological, optical and biochemical approaches. Distal dendrites of iSPNs from symptomatic HD mice were hypoexcitable, a change that was attributable to increased association of dendritic Kv4 potassium channels with auxiliary KChIP subunits. This association was negatively modulated by TrkB receptor signaling. Dendritic excitability of HD iSPNs was rescued …

Down Syndrome Mouse Models Have An Abnormal Enteric Nervous System, Ellen M Schill, Christina M Wright, Alisha Jamil, Jonathan M Lacombe, Randall J Roper, Robert O Heuckeroth

Open Access Publications

Children with trisomy 21 (Down syndrome [DS]) have a 130-fold increased incidence of Hirschsprung Disease (HSCR), a developmental defect where the enteric nervous system (ENS) is missing from distal bowel (i.e., distal bowel is aganglionic). Treatment for HSCR is surgical resection of aganglionic bowel, but many children have bowel problems after surgery. Post-surgical problems like enterocolitis and soiling are especially common in children with DS. To determine how trisomy 21 affects ENS development, we evaluated the ENS in two DS mouse models, Ts65Dn and Tc1. These mice are trisomic for many chromosome 21 homologous genes, including Dscam and Dyrk1a, which …

Detection Of Pediatric Upper Extremity Motor Activity And Deficits With Accelerometry, Catherine R. Hoyt, Andrew N. Van, Mario Ortega, Jonathan M. Koller, Elyse A. Everett, Annie L. Nguyen, Catherine E. Lang, Bradley L. Schlaggar, Nico U.F. Dosenbach

Open Access Publications

Importance: Affordable, quantitative methods to screen children for developmental delays are needed. Motor milestones can be an indicator of developmental delay and may be used to track developmental progress. Accelerometry offers a way to gather real-world information about pediatric motor behavior.

Objective: To develop a referent cohort of pediatric accelerometry from bilateral upper extremities (UEs) and determine whether movement can accurately distinguish those with and without motor deficits.

Design, Setting, and Participants: Children aged 0 to 17 years participated in a prospective cohort from December 8, 2014, to December 29, 2017. Children were recruited from Ranken Jordan Pediatric Bridge Hospital, …

Subsequent Event Risk In Individuals With Established Coronary Heart Disease, Riyaz S. Patel, Petra A. Lenzini, Sharon Cresci, Et Al

Open Access Publications

No abstract provided.

A Heteroscedastic Hidden Markov Mixture Model For Responses And Categorized Response Times, Dylan Molenaar, Sandor Rózsa, Maria Bolsinova

Open Access Publications

Various mixture modeling approaches have been proposed to identify within-subjects differences in the psychological processes underlying responses to psychometric tests. Although valuable, the existing mixture models are associated with at least one of the following three challenges: (1) A parametric distribution is assumed for the response times that-if violated-may bias the results; (2) the response processes are assumed to result in equal variances (homoscedasticity) in the response times, whereas some processes may produce more variability than others (heteroscedasticity); and (3) the different response processes are modeled as independent latent variables, whereas they may be related. Although each of these challenges …

Sex Differences In Functional Connectivity During Fetal Brain Development, M D Wheelock, J L Hect, E Hernandez-Andrade, S S Hassan, R Romero, A T Eggebrecht, M E Thomason

Open Access Publications

Sex-related differences in brain and behavior are apparent across the life course, but the exact set of processes that guide their emergence in utero remains a topic of vigorous scientific inquiry. Here, we evaluate sex and gestational age (GA)-related change in functional connectivity (FC) within and between brain wide networks. Using resting-state functional magnetic resonance imaging we examined FC in 118 human fetuses between 25.9 and 39.6 weeks GA (70 male; 48 female). Infomap was applied to the functional connectome to identify discrete prenatal brain networks in utero. A consensus procedure produced an optimal model comprised of 16 distinct fetal …

A Mixture Of U.S. Food And Drug Administration-Approved Monoaminergic Drugs Protects The Retina From Light Damage In Diverse Models Of Night Blindness, Henri Leinonen, Elliot H. Choi, Anthony Gardella, Vladimir J. Kefalov, Krzysztof Palczewski

Open Access Publications

Purpose: The purpose of this study was to test the extent of light damage in different models of night blindness and apply these paradigms in testing the therapeutic efficacy of combination therapy by drugs acting on the Gi, Gs, and Gq protein-coupled receptors.

Methods: Acute bright light exposure was used to test susceptibility to light damage in mice lacking the following crucial phototransduction proteins: rod transducin (GNAT1), cone transducin (GNAT2), visual arrestin 1 (ARR1), and rhodopsin kinase 1 (GRK1). Mice were intraperitoneally injected with either vehicle or drug combination consisting of metoprolol (β1-receptor antagonist), bromocriptine (dopamine family-2 receptor agonist) and …

Abnormal Oxidative Metabolism In A Quiet Genomic Background Underlies Clear Cell Papillary Renal Cell Carcinoma, Jianing Xu, James J. Hsieh, Et Al

Open Access Publications

No abstract provided.

Neurotransmitter Identity Is Acquired In A Lineage-Restricted Manner In The Drosophila Cns, Haluk Lacin, Hui-Min Chen, Xi Long, Robert H. Singer, Tzumin Lee, James W. Truman

Open Access Publications

The vast majority of the adult fly ventral nerve cord is composed of 34 hemilineages, which are clusters of lineally related neurons. Neurons in these hemilineages use one of the three fast-acting neurotransmitters (acetylcholine, GABA, or glutamate) for communication. We generated a comprehensive neurotransmitter usage map for the entire ventral nerve cord. We did not find any cases of neurons using more than one neurotransmitter, but found that the acetylcholine specific gene ChAT is transcribed in many glutamatergic and GABAergic neurons, but these transcripts typically do not leave the nucleus and are not translated. Importantly, our work uncovered a simple …

Network Meta-Analysis Of Randomised Trials Of Pharmacological, Psychotherapeutic, Exercise And Collaborative Care Interventions For Depressive Symptoms In Patients With Coronary Artery Disease: Hybrid Systematic Review Of Systematic Reviews Protocol, Frank Doyle, Kenneth Freedland, Robert Carney, Peter De Jonge, Chris Dickens, Susanne Pedersen, Jan Sorensen, Martin Dempster

Open Access Publications

BACKGROUND: Depression is common in patients with coronary artery disease (CAD) and is associated with poorer outcomes and higher costs. Several randomised controlled trials (RCTs) targeting depression, of various modalities (including pharmacological, psychotherapeutic and other approaches), have been conducted and summarised in pairwise meta-analytic reviews. However, no study has considered the cumulative evidence within a network, which can provide valuable indirect comparisons and information about the relative efficacy of interventions. Therefore, we will adopt a review of review methodology to develop a network meta-analysis (NMA) of depression interventions for depression in CAD.

METHODS: We will search relevant databases from inception …

Homozygous Frameshift Mutations In Fat1 Cause A Syndrome Characterized By Colobomatous-Microphthalmia, Ptosis, Nephropathy And Syndactyly., Najim Lahrouchi, Aman George, Ilham Ratbi, Ronen Schneider, Siham C Elalaoui, Shahida Moosa, Sanita Bharti, Ruchi Sharma, Mones Abu-Asab, Felix Onojafe, Najlae Adadi, Elisabeth M Lodder, Fatima-Zahra Laarabi, Yassine Lamsyah, Hamza Elorch, Imane Chebbar, Alex V Postma, Vassilios Lougaris, Alessandro Plebani, Janine Altmueller, Henriette Kyrieleis, Vardiella Meiner, Helen Mcneill, Kapil Bharti, Stanislas Lyonnet, Bernd Wollnik, Alexandra Henrion-Caude, Amina Berraho, Friedhelm Hildebrandt, Connie R Bezzina, Brian P Brooks, Abdelaziz Sefiani

Open Access Publications

A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated with homozygous frameshift mutations in FAT1. We show that Fat1 knockout mice and zebrafish embryos homozygous for truncating fat1a mutations exhibit completely penetrant coloboma, recapitulating the most consistent developmental defect observed in affected individuals. In human retinal pigment epithelium (RPE) cells, the primary site for the fusion of optic fissure margins, FAT1 is localized at earliest cell-cell junctions, consistent with a role in facilitating optic …

Temperoammonic Stimulation Depotentiates Schaffer Collateral Ltp Via P38 Mapk Downstream Of Adenosine A1 Receptors, Yukitoshi Izumi, Charles F. Zorumski

Open Access Publications

We previously found that low-frequency stimulation of direct temperoammonic (TA) inputs to hippocampal area CA1 depotentiates previously established long-term potentiation in the Schaffer collateral (SC) pathway through complex signaling involving dopamine, endocannabinoids, neuregulin-1, GABA, and adenosine, with adenosine being the most distal modulator identified to date. In the present studies, we examined mechanisms contributing to the effects of adenosine in hippocampal slices from male albino rats. We found that extracellular conversion of ATP to adenosine via an ectonucleotidase contributes significantly to TA-mediated SC depotentiation and the depotentiation resulting from block of adenosine transport. Adenosine-mediated SC depotentiation does not involve activation …

Association Of The Infant Gut Microbiome With Early Childhood Neurodevelopmental Outcomes: An Ancillary Study To The Vdaart Randomized Clinical Trial, Joanne E. Sordillo, Susan Korrick, Nancy Laranjo, Vincent Carey, George M. Weinstock, Diane R. Gold, George O'Connor, Megan Sandel, Leonard B. Bacharier, Avraham Beigelman, Robert Zeiger, Augusto A. Litonjua, Scott T. Weiss

Open Access Publications

Importance: In animal models, the early life gut microbiome influences later neurodevelopment. Corresponding data in human populations are lacking.

Objective: To study associations between the gut microbiome in infants and development at preschool age measured by the Ages and Stages Questionnaire, third edition (ASQ-3).

Design, Setting, and Participants: This ancillary cohort study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART) used data from 715 participants who had development assessed at 3 years of age by the ASQ-3, which included scores in 5 domains (gross motor skills, fine motor skills, problem solving, communication, and personal and social skills). A total …