Digital Commons Network^™

Healthy Dietary Patterns Are Associated With Exposure To Environmental Chemicals In A Pregnancy Cohort, Guoqi Yu, Ruijin Lu, Jiaxi Yang, Mohammad L Rahman, Ling-Jun Li, Dong D Wang, Qi Sun, Wei Wei Pang, Claire Guivarch, Anna Birukov, Jagteshwar Grewal, Zhen Chen, Cuilin Zhang

2020-Current year OA Pubs

Healthy dietary patterns, such as the alternate Mediterranean diet and alternate Healthy Eating Index, benefit cardiometabolic health. However, several food components of these dietary patterns are primary sources of environmental chemicals. Here, using data from a racially and ethnically diverse US cohort, we show that healthy dietary pattern scores were positively associated with plasma chemical exposure in pregnancy, particularly for the alternate Mediterranean diet and alternate Healthy Eating Index with polychlorinated biphenyls and per- and poly-fluoroalkyl substances. The associations appeared stronger among Asian and Pacific Islanders. These findings suggest that optimizing the benefits of a healthy diet requires concerted regulatory …

Plasmacytoid Dendritic Cells Control Homeostasis Of Megakaryopoiesis, Florian Gaertner, Marco Colonna, Et Al.

2020-Current year OA Pubs

Platelet homeostasis is essential for vascular integrity and immune defence

Cognitive Control Training With Domain-General Response Inhibition Does Not Change Children's Brains Or Behavior, Keertana Ganesan, Abigail Thompson, Claire R Smid, Roser Cañigueral, Yongjing Li, Grace Revill, Vanessa Puetz, Boris C Bernhardt, Nico U F Dosenbach, Rogier Kievit, Nikolaus Steinbeis

2020-Current year OA Pubs

Cognitive control is required to organize thoughts and actions and is critical for the pursuit of long-term goals. Childhood cognitive control relates to other domains of cognitive functioning and predicts later-life success and well-being. In this study, we used a randomized controlled trial to test whether cognitive control can be improved through a pre-registered 8-week intervention in 235 children aged 6-13 years targeting response inhibition and whether this leads to changes in multiple behavioral and neural outcomes compared to a response speed training. We show long-lasting improvements of closely related measures of cognitive control at the 1-year follow-up; however, training …

A Bistable Inhibitory Optogpcr For Multiplexed Optogenetic Control Of Neural Circuits, Jonas Wietek, Bobbie J Brown, Bryan A Copits, Et Al.

2020-Current year OA Pubs

Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein-coupled receptor pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin (PdCO) is an efficient, versatile, light-activated bistable G-protein-coupled receptor that can suppress synaptic transmission in mammalian neurons with …

Momelotinib Vs. Ruxolitinib In Myelofibrosis Patient Subgroups By Baseline Hemoglobin Levels In The Simplify-1 Trial, Vikas Gupta, Stephen Oh, Et Al.

2020-Current year OA Pubs

A key hallmark of myelofibrosis is anemia, which ranges from mild to severe based on hemoglobin levels. To more clearly define outcomes with the Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib by anemia severity, we performed a descriptive post hoc exploratory analysis of the double-blind, randomized, phase 3 SIMPLIFY-1 study (NCT01969838;

Vaso-Lock For Sutureless Anastomosis In A Pig Arteriovenous Loop Model, Xiaowei Li, Emma R Young, Cameron Martin, Joseph G Ribaudo, Mohamed Zaghloul, Sophia Roberts, Rodrigo Meade, Batool Arif, William R Moritz, Sarah Madira, Jonathon B Schofield, Mohamed A Zayed, Justin M Sacks, Et Al.

2020-Current year OA Pubs

A vascular anastomosis is a critical surgical skill that involves connecting blood vessels. Traditional handsewn techniques can be challenging and resource intensive. To address these issues, we have developed a unique sutureless anastomotic device called Vaso-Lock. This intraluminal device connects free vascular ends using anchors to maintain traction and enable a rapid anastomosis. We tested the anastomotic capability of Vaso-Locks in a pig common carotid-internal jugular arteriovenous model. The use of Vaso-Lock allowed us to accomplish this procedure in less than 10 min, in contrast to the approximately 40 min required for a handsewn anastomosis. The Vaso-Lock effectively maintained patency …

Replication And Reliability Of Parkinson's Disease Clinical Subtypes, Therese V Cash, Christina N Lessov-Schlaggar, Erin R Foster, Peter S Myers, Joshua J Jackson, Baijayanta Maiti, Paul T Kotzbauer, Joel S Perlmutter, Meghan C Campbell

2020-Current year OA Pubs

BACKGROUND: We recently identified three distinct Parkinson's disease subtypes: "motor only" (predominant motor deficits with intact cognition and psychiatric function); "psychiatric & motor" (prominent psychiatric symptoms and moderate motor deficits); "cognitive & motor" (cognitive and motor deficits).

OBJECTIVE: We used an independent cohort to replicate and assess reliability of these Parkinson's disease subtypes.

METHODS: We tested our original subtype classification with an independent cohort (N = 100) of Parkinson's disease participants without dementia and the same comprehensive evaluations assessing motor, cognitive, and psychiatric function. Next, we combined the original (N = 162) and replication (N = 100) datasets to test …

Poglut2/3 Double Knockout In Mice Results In Neonatal Lethality With Reduced Levels Of Fibrillin In Lung Tissues, Sanjiv Neupane, Daniel B Williamson, Robyn A Roth, Carmen M Halabi, Robert S Haltiwanger, Bernadette C Holdener

2020-Current year OA Pubs

Fibrillin microfibrils play a critical role in the formation of elastic fibers, tissue/organ development, and cardiopulmonary function. These microfibrils not only provide structural support and flexibility to tissues, but they also regulate growth factor signaling through a plethora of microfibril-binding proteins in the extracellular space. Mutations in fibrillins are associated with human diseases affecting cardiovascular, pulmonary, skeletal, and ocular systems. Fibrillins consist of up to 47 epidermal growth factor-like repeats, of which more than half are modified by protein O-glucosyltransferase 2 (POGLUT2) and/or POGLUT3. Loss of these modifications reduces secretion of N-terminal fibrillin constructs overexpressed in vitro. Here, we investigated …

Diagnostic Efficacy And Clinical Impact Of Image-Guided Core Needle Biopsy Of Suspected Vertebral Osteomyelitis, Winston L Winkler, Ige A George, Sumanth Gandra, Jonathan C Baker, Anderanik Tomasian, Benjamin Northrup, Theodore L Vander Velde, Travis J Hillen, Chongliang Luo, Resten Imaoka, Gino M Dettorre, Jack W Jennings

2020-Current year OA Pubs

OBJECTIVES: The diagnostic yield and clinical impact of image-guided core needle biopsy (ICNB) of suspected vertebral osteomyelitis in adults is heterogenous in published studies owing to small sample sizes, indicating the need for large cohort studies.

METHODS: A retrospective analysis of ICNBs was performed from 2010 to 2021 for patients with imaging findings consistent with vertebral osteomyelitis. For each biopsy, a series of factors were analyzed, as well as if histopathology was diagnostic of osteomyelitis and if microbiological cultures were positive. In addition, it was recorded in what way biopsy influenced clinical management regarding antimicrobial treatment. A multivariate statistical analysis …

Study Of A Pst-Trained Voice-Enabled Artificial Intelligence Counselor For Adults With Emotional Distress (Speac-2): Design And Methods, Corina R Ronneberg, Thomas Kannampallil, Et Al.

2020-Current year OA Pubs

BACKGROUND: Novel and scalable psychotherapies are urgently needed to address the depression and anxiety epidemic. Leveraging artificial intelligence (AI), a voice-based virtual coach named Lumen was developed to deliver problem solving treatment (PST). The first pilot trial showed promising changes in cognitive control measured by functional neuroimaging and improvements in depression and anxiety symptoms.

METHODS: To further validate Lumen in a 3-arm randomized clinical trial, 200 participants with mild-to-moderate depression and/or anxiety will be randomly assigned in a 2:1:1 ratio to receive Lumen-coached PST, human-coached PST as active treatment comparison, or a waitlist control condition where participants can receive Lumen …

Il2 Targeted To Cd8+ T Cells Promotes Robust Effector T-Cell Responses And Potent Antitumor Immunity, Kelly D Moynihan, Hussein Sultan, Robert D Schreiber, Et Al.

2020-Current year OA Pubs

IL2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, whereas others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL2 to CD8+ T cells, which are key antitumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, a CD8 cis-targeted IL2 that demonstrates over 500-fold preference for CD8+ T cells over natural killer and regulatory T cells (Tregs), which may contribute to toxicity and immunosuppression, respectively. AB248 recapitulated IL2's effects on CD8+ T cells in vitro and induced selective expansion of CD8+T cells …

A Phase Ii Trial Of The Wee1 Inhibitor Adavosertib In Setd2-Altered Advanced Solid Tumor Malignancies (Nci 10170), Edward Maldonado, Nikolaos A Trikalinos, Et Al.

2020-Current year OA Pubs

UNLABELLED: We sought to evaluate the efficacy of WEE1 inhibitor adavosertib in patients with solid tumor malignancies (cohort A) and clear cell renal cell carcinoma (ccRCC; cohort B). NCT03284385 was a parallel cohort, Simon two-stage, phase II study of adavosertib (300 mg QDAY by mouth on days 1-5 and 8-12 of each 21-day cycle) in patients with solid tumor malignancies harboring a pathogenic SETD2 mutation. The primary endpoint was the objective response rate. Correlative assays evaluated the loss of H3K36me3 by IHC, a downstream consequence of SETD2 loss, in archival tumor tissue. Eighteen patients were enrolled (9/cohort). The median age …

Origins Of Cancer: Ain't It Just Mature Cells Misbehaving?, Charles J Cho, Jeffrey W Brown, Jason C Mills

2020-Current year OA Pubs

A pervasive view is that undifferentiated stem cells are alone responsible for generating all other cells and are the origins of cancer. However, emerging evidence demonstrates fully differentiated cells are plastic, can be coaxed to proliferate, and also play essential roles in tissue maintenance, regeneration, and tumorigenesis. Here, we review the mechanisms governing how differentiated cells become cancer cells. First, we examine the unique characteristics of differentiated cell division, focusing on why differentiated cells are more susceptible than stem cells to accumulating mutations. Next, we investigate why the evolution of multicellularity in animals likely required plastic differentiated cells that maintain …

Phase 1b Study To Assess The Safety, Tolerability, And Clinical Activity Of Pamiparib In Combination With Temozolomide In Patients With Locally Advanced Or Metastatic Solid Tumors, Agostina Stradella, Haeseong Park, Et Al.

2020-Current year OA Pubs

BACKGROUND: Pamiparib is a potent, selective, poly (ADP-ribose) polymerase 1/2 inhibitor that demonstrates synthetic lethality in cells with breast cancer susceptibility gene mutations or other homologous recombination deficiency. This two-stage phase 1b study (NCT03150810) assessed pamiparib in combination with temozolomide (TMZ) in adult patients with histologically confirmed locally advanced and metastatic solid tumors.

METHODS: Oral pamiparib 60 mg was administered twice daily. During the dose-escalation stage, increasing doses of TMZ (40-120 mg once daily pulsed or 20-40 mg once daily continuous) were administered to determine the recommended dose to be administered in the dose-expansion stage. The primary objectives were to …

Liver Disease And Transplantation In Telomere Biology Disorders: An International Multicenter Cohort, Yunzu Michele Wang, Steven K Brennan, Sakil Kulkarni, Et Al.

2020-Current year OA Pubs

BACKGROUND: Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes.

METHODS: Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study.

RESULTS: Group A ("Advanced") included 40 patients with advanced liver disease. Of …

A Survey Of Availability And Affordability Of Polypills For Cardiovascular Disease In Selected Countries, Gautam Satheesh, Bishal Gyawali, Marie France Chan Sun, Mark D Huffman, Amitava Banerjee, Pablo Perel, Adrianna Murphy

2020-Current year OA Pubs

BACKGROUND: The recent inclusion of polypills-fixed-dose combinations of antihypertensive medicines and a statin with or without aspirin-in the World Health Organization's Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for cardiovascular diseases (CVDs). Although there exists extensive evidence on the effectiveness, safety and acceptability of polypills, there has been no research to date assessing the real-world availability and affordability of polypills globally.

METHODS: We conducted a cross-sectional survey, based on the WHO/Health Action International methodology, in 13 countries around the world. In the surveyed countries, we first ascertained whether any polypill was authorised …

Spinal Calcifying Pseudoneoplasms Of The Neuraxis: A Case Report And Review Of The Literature, Ajay Chatrath, Mackenzie Lemieux, Rujvee P Patel, Kaleigh F Roberts, Sonika Dahiya, Brenton Pennicooke

2020-Current year OA Pubs

Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, non-neoplastic, slow-growing tumors that can present anywhere throughout the central nervous system. While the etiology of these lesions remains unknown, the mainstay of treatment is surgical excision. We describe a case of CAPNON at our institution in a 66 year-old female patient who presented with 5 months of pain and burning sensation in her thigh. On MRI, an intradural extramedullary lesion was identified at the level of T11-T12. The mass was surgically excised and the patient reported resolution of her symptoms by her six week follow-up appointment. We reviewed 79 spinal CAPNON …

A Pilot Study Of Nintedanib In Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer, Christine Auberle, Feng Gao, Mark Sloan, Daniel Morgensztern, Linda Winkler, Jeffrey P. Ward, Siddhartha Devarakonda, Timothy P. Rearden, Ramaswamy Govindan, Saiama N. Waqar

2020-Current year OA Pubs

BACKGROUND: Nintedanib is a small molecule tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in

METHODS: Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with the above mutations were enrolled. Exclusion criteria included necrotic tumors with invasion of blood vessels, history of recent thromboembolic events, increased risk of bleeding or thrombosis, myocardial infarction, and weight loss >10% within past 6 months. Nintedanib was …

Motor Competence Is Related To Acquisition Of Error-Based But Not Reinforcement Learning In Children Ages 6 To 12, Jeffrey D Konrad, Natasha Marrus, Keith R Lohse, Kayla M Thuet, Catherine E Lang

2020-Current year OA Pubs

BACKGROUND: An essential component of childhood development is increasing motor competence. Poor motor learning is often thought to underlie impaired motor competence, but this link is unclear in previous studies.

AIMS: Our aim was to test the relationship between motor competence and motor learning in the acquisition phase. Both reinforcement learning (RL) and error-based learning (EBL) were tested. We hypothesized that slower RL and slower EBL acquisition rates would relate to lower motor competence.

METHODS AND PROCEDURES: Eighty-six participants ages 6-12 performed a target throwing task under RL and EBL conditions. The Movement Assessment Battery for Children - 2nd edition …

Extracorporeal Membrane Oxygenation For Respiratory Failure: A Narrative Review, John C Grotberg, Daniel Reynolds, Bryan D Kraft

2020-Current year OA Pubs

Extracorporeal membrane oxygenation support for respiratory failure in the intensive care unit continues to have an expanded role in select patients. While acute respiratory distress syndrome remains the most common indication, extracorporeal membrane oxygenation may be used in other causes of refractory hypoxemia and/or hypercapnia. The most common configuration is veno-venous extracorporeal membrane oxygenation; however, in specific cases of refractory hypoxemia or right ventricular failure, some patients may benefit from veno-pulmonary extracorporeal membrane oxygenation or veno-venoarterial extracorporeal membrane oxygenation. Patient selection and extracorporeal circuit management are essential to successful outcomes. This narrative review explores the physiology of extracorporeal membrane oxygenation, …

Python Tooth-Inspired Fixation Device For Enhanced Rotator Cuff Repair, Iden Kurtaliaj, Ethan D Hoppe, Yuxuan Huang, David Ju, Jacob A Sandler, Donghwan Yoon, Guy M Genin

2020-Current year OA Pubs

Rotator cuff repair surgeries fail frequently, with 20 to 94% of the 600,000 repairs performed annually in the United States resulting in retearing of the rotator cuff. The most common cause of failure is sutures tearing through tendons at grasping points. To address this issue, we drew inspiration from the specialized teeth of snakes of the Pythonoidea superfamily, which grasp soft tissues without tearing. To apply this nondamaging gripping approach to the surgical repair of tendon, we developed and optimized a python tooth-inspired device as an adjunct to current rotator cuff suture repair and found that it nearly doubled repair …

Obesity Is Associated With Muscle Atrophy In Rotator Cuff Tear, Simone D Herzberg, Robert H Brophy, Matthew V Smith, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The primary goal of this study is to evaluate the relationship between Body Mass Index (BMI) and muscle atrophy in individuals with rotator cuff tears.

METHODS: This study consists of patients with rotator cuff tears identified by MRI from two independent cohorts, the Rotator Cuff Outcomes Workgroup (ROW) and the Multicenter Orthopaedic Outcomes Network (MOON). Presence of atrophy (yes/no) and severity of atrophy (as an ordinal variable) were assessed on MRI by expert physicians. We used multivariable regression models to evaluate the relationship between BMI and muscle atrophy while adjusting for age and sex in each study, conducted sensitivity …

Detection Of Early-Stage Nash Using Non-Invasive Hyperpolarized 13c Metabolic Imaging, Cornelius Von Morze, Tyler Blazey, Ashley Shaw, William M Spees, Kooresh I Shoghi, Michael A Ohliger

2020-Current year OA Pubs

Non-alcoholic steatohepatitis (NASH) is characterized from its early stages by a profound remodeling of the liver microenvironment, encompassing changes in the composition and activities of multiple cell types and associated gene expression patterns. Hyperpolarized (HP)

Real-World And Clinical Trial Outcomes In Large B-Cell Lymphoma With Axicabtagene Ciloleucel Across Race And Ethnicity, Frederick L Locke, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients who received axi-cel between 2017 and 2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 trials, respectively. Overall survival …

Examining Associations Between Smartphone Use And Clinical Severity In Frontotemporal Dementia: Proof-Of-Concept Study, Emily W Paolillo, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

BACKGROUND: Frontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged <65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with mild cognitive impairment show that declining function is reflected in reduced computer use; however, associations with smartphone use are unknown.

OBJECTIVE: This study aims to characterize daily trajectories in smartphone battery use, a proxy for smartphone use, and examine relationships with clinical indicators of severity in FTLD.

METHODS: Participants were 231 adults (mean age 52.5, SD 14.9 years; n=94, 40.7% men; n=223, 96.5% non-Hispanic White) enrolled in the Advancing Research and Treatment of Frontotemporal Lobar Degeneration (ARTFL study) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS study) Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Mobile App study, including 49 (21.2%) with mild neurobehavioral changes and no functional …

Dorsal Raphe Neurons Integrate The Values Of Reward Amount, Delay, And Uncertainty In Multi-Attribute Decision-Making, Yang-Yang Feng, Ethan S Bromberg-Martin, Ilya E Monosov

2020-Current year OA Pubs

The dorsal raphe nucleus (DRN) is implicated in psychiatric disorders that feature impaired sensitivity to reward amount, impulsivity when facing reward delays, and risk-seeking when confronting reward uncertainty. However, it has been unclear whether and how DRN neurons signal reward amount, reward delay, and reward uncertainty during multi-attribute value-based decision-making, where subjects consider these attributes to make a choice. We recorded DRN neurons as monkeys chose between offers whose attributes, namely expected reward amount, reward delay, and reward uncertainty, varied independently. Many DRN neurons signaled offer attributes, and this population tended to integrate the attributes in a manner that reflected …

Role Of The Afferent Lymph As An Immunological Conduit To Analyze Tissue Antigenic And Inflammatory Load, Padma P Nanaware, Cheryl F Lichti, Xiaoxiao Wan, Emil R Unanue, Et Al.

2020-Current year OA Pubs

The lymphatic fluid is the conduit by which part of the tissue "omics" is transported to the draining lymph node for immunosurveillance. Following cannulation of the pre-nodal cervical and mesenteric afferent lymphatics, herein we investigate the lymph proteomic composition, uncovering that its composition varies according to the tissue of origin. Tissue specificity is also reflected in the dendritic cell-major histocompatibility complex class II-eluted immunopeptidome harvested from the cervical and mesenteric nodes. Following inflammatory disruption of the gut barrier, the lymph antigenic and inflammatory loads are analyzed in both mice and subjects with inflammatory bowel diseases. Gastrointestinal tissue damage reflects the …

Airy-Beam Holographic Sonogenetics For Advancing Neuromodulation Precision And Flexibility, Zhongtao Hu, Yaoheng Yang, Leqi Yang, Yan Gong, Chinwendu Chukwu, Dezhuang Ye, Yimei Yue, Jinyun Yuan, Alexxai V Kravitz, Hong Chen

2020-Current year OA Pubs

Advancing our understanding of brain function and developing treatments for neurological diseases hinge on the ability to modulate neuronal groups in specific brain areas without invasive techniques. Here, we introduce Airy-beam holographic sonogenetics (AhSonogenetics) as an implant-free, cell type-specific, spatially precise, and flexible neuromodulation approach in freely moving mice. AhSonogenetics utilizes wearable ultrasound devices manufactured using 3D-printed Airy-beam holographic metasurfaces. These devices are designed to manipulate neurons genetically engineered to express ultrasound-sensitive ion channels, enabling precise modulation of specific neuronal populations. By dynamically steering the focus of Airy beams through ultrasound frequency tuning, AhSonogenetics is capable of modulating neuronal populations …

A Shared Group Of Bacterial Taxa In The Duodenal Microbiota Of Undernourished Pakistani Children With Environmental Enteric Dysfunction, Najeeha T Iqbal, Robert Y Chen, Nicholas W Griffin, Matthew C Hibberd, Michael J Barratt, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Environmental enteric dysfunction (EED) is a subclinical syndrome of altered small intestinal function postulated to be an important contributor to childhood undernutrition. The role of small intestinal bacterial communities in the pathophysiology of EED is poorly defined due to a paucity of studies where there has been a direct collection of small intestinal samples from undernourished children. Sixty-three members of a Pakistani cohort identified as being acutely malnourished between 3 and 6 months of age and whose wasting (weight-for-length

Injury-Induced Foxm1 Expression In The Mouse Kidney Drives Epithelial Proliferation By A Cyclin F-Dependent Mechanism, Megan L. Noonan, Yoshiharu Muto, Yasuhiro Yoshimura, Aidan Leckie-Harre, Haojia Wu, Vladimir V. Kalinichenko, Benjamin D. Humphreys, Monica Chang-Panesso

2020-Current year OA Pubs

Acute kidney injury (AKI) strongly upregulates the transcription factor Foxm1 in the proximal tubule in vivo, and Foxm1 drives epithelial proliferation in vitro. Here, we report that deletion of Foxm1 either with a nephron-specific Cre driver or by inducible global deletion reduced proximal tubule proliferation after ischemic injury in vivo. Foxm1 deletion led to increased AKI to chronic kidney disease transition, with enhanced fibrosis and ongoing tubule injury 6 weeks after injury. We report ERK mediated FOXM1 induction downstream of the EGFR in primary proximal tubule cells. We defined FOXM1 genomic binding sites by cleavage under targets and release using …