Digital Commons Network^™

Functional And Clinical Studies Reveal Pathophysiological Complexity Of Clcn4-Related Neurodevelopmental Condition, Elizabeth E Palmer, Linda J Richards, Et Al.

2020-Current year OA Pubs

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on …

Dissecting Cell Identity Via Network Inference And In Silico Gene Perturbation, Kenji Kamimoto, Blerta Stringa, Christy M Hoffmann, Kunal Jindal, Lilianna Solnica-Krezel, Samantha A Morris

2020-Current year OA Pubs

Cell identity is governed by the complex regulation of gene expression, represented as gene-regulatory networks

Identification Of Bradycardia Following Remdesivir Administration Through The Us Food And Drug Administration American College Of Medical Toxicology Covid-19 Toxic Pharmacovigilance Project, Jason M Devgun, Rongmei Zhang, Jeffrey Brent, Paul Wax, Keith Burkhart, Alison Meyn, Sharan Campleman, Stephanie Abston, Kim Aldy, Toxicology Investigators Consortium Fact Study Group

2020-Current year OA Pubs

IMPORTANCE: The rapid spread and mortality associated with COVID-19 emphasized a need for surveillance system development to identify adverse events (AEs) to emerging therapeutics. Bradycardia is a remdesivir infusion-associated AE listed in the US Food and Drug Administration-approved prescribing information.

OBJECTIVE: To evaluate the magnitude and duration of bradycardic events following remdesivir administration.

DESIGN, SETTING, AND PARTICIPANTS: A multicenter cohort study of patients with recorded heart rate less than 60 beats per minute within 24 hours after administration of a remdesivir dose was conducted between November 23, 2020, and October 31, 2021. Participants included patients hospitalized with COVID-19 at 15 …

Early Intervention And Intensive Management Of Patients With Diabetes, Cardiorenal, And Metabolic Diseases, Yehuda Handelsman, Samuel Klein, Et Al.

2020-Current year OA Pubs

Increasing rates of obesity and diabetes have driven corresponding increases in related cardiorenal and metabolic diseases. In many patients, these conditions occur together, further increasing morbidity and mortality risks to the individual. Yet all too often, the risk factors for these disorders are not addressed promptly in clinical practice, leading to irreversible pathologic progression. To address this gap, we convened a Task Force of experts in cardiology, nephrology, endocrinology, and primary care to develop recommendations for early identification and intervention in obesity, diabetes, and other cardiorenal and metabolic diseases. The recommendations include screening and diagnosis, early interventions with lifestyle, and …

Human Cardiac Pericytes Are Susceptible To Sars-Cov-2 Infection, Brittany D Brumback, Oleksandr Dmytrenko, Ashley N Robinson, Adam L Bailey, Pan Ma, Jing Liu, Stephanie C Hicks, Sherwin Ng, Gang Li, David M Zhang, Catherine E Lipovsky, Chieh-Yu Lin, Michael S Diamond, Kory J Lavine, Stacey L Rentschler

2020-Current year OA Pubs

COVID-19 is associated with serious cardiovascular complications, with incompletely understood mechanism(s). Pericytes have key functions in supporting endothelial cells and maintaining vascular integrity. We demonstrate that human cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. Viral entry into pericytes is mediated by endosomal proteases, and infection leads to up-regulation of inflammatory markers, vasoactive mediators, and nuclear factor kappa-B-dependent cell death. Furthermore, we present evidence of cardiac pericyte infection in COVID-19 myocarditis patients. These data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a role for pericyte infection in COVID-19.

Genetic And Environmental Variation In Continuous Phenotypes In The Abcd Study®, Hermine H M Maes, Dana M Lapato, J Eric Schmitt, Monica Luciana, Marie T Banich, James M Bjork, John K Hewitt, Pamela A Madden, Andrew C Heath, Deanna M Barch, Wes K Thompson, William G Iacono, Michael C Neale

2020-Current year OA Pubs

Twin studies yield valuable insights into the sources of variation, covariation and causation in human traits. The ABCD Study® (abcdstudy.org) was designed to take advantage of four universities known for their twin research, neuroimaging, population-based sampling, and expertise in genetic epidemiology so that representative twin studies could be performed. In this paper we use the twin data to: (i) provide initial estimates of heritability for the wide range of phenotypes assessed in the ABCD Study using a consistent direct variance estimation approach, assuring that both data and methodology are sound; and (ii) provide an online resource for researchers that can …

In Vivo Editing Of The Pan-Endothelium By Immunity Evading Simian Adenoviral Vector, Reka Lorincz, Aluet Borrego Alvarez, Christopher J Walkey, Samir A Mendonça, Zhi Hong Lu, Alexa E Martinez, Cecilia Ljungberg, Jason D Heaney, William R Lagor, David T Curiel

2020-Current year OA Pubs

Biological applications deriving from the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 site-specific nuclease system continue to impact and accelerate gene therapy strategies. Safe and effective in vivo co-delivery of the CRISPR/Cas9 system to target somatic cells is essential in the clinical therapeutic context. Both non-viral and viral vector systems have been applied for this delivery matter. Despite elegant proof-of-principle studies, available vector technologies still face challenges that restrict the application of CRISPR/Cas9-facilitated gene therapy. Of note, the mandated co-delivery of the gene-editing components must be accomplished in the potential presence of pre-formed anti-vector immunity. Additionally, methods must be sought …

The Insurance Landscape For Implant- And Autologous-Based Breast Reconstruction In The United States, Louisa C. Boyd, Jason A. Greenfield, Sravya S. Ainapurapu, Rachel Skladman, Gary Skolnick, Durai Sundaramoorthi, Justin M. Sacks

2020-Current year OA Pubs

UNLABELLED: Insurance coverage of postmastectomy breast reconstruction is mandated in America, regardless of reconstructive modality. Despite enhanced patient-reported outcomes, autologous reconstruction is utilized less than nonautologous reconstruction nationally. Lower reimbursement from Medicare and Medicaid may disincentivize autologous-based reconstruction. This study examines the impact of insurance and sociodemographic factors on breast reconstruction.

METHODS: A retrospective analysis of the Healthcare Cost and Utilization Project National Inpatient Sample Database from 2014 to 2017 was performed. International Classification of Diseases Clinical Modification and Procedure Coding System codes were used to identify patients for inclusion. De-identified sociodemographic and insurance data were analyzed using

RESULTS: In …

Autophagy Requirements For Eye Lens Differentiation And Transparency, Lisa Brennan, M Joseph Costello, J Fielding Hejtmancik, A Sue Menko, S Amer Riazuddin, Alan Shiels, Marc Kantorow

2020-Current year OA Pubs

Recent evidence points to autophagy as an essential cellular requirement for achieving the mature structure, homeostasis, and transparency of the lens. Collective evidence from multiple laboratories using chick, mouse, primate, and human model systems provides evidence that classic autophagy structures, ranging from double-membrane autophagosomes to single-membrane autolysosomes, are found throughout the lens in both undifferentiated lens epithelial cells and maturing lens fiber cells. Recently, key autophagy signaling pathways have been identified to initiate critical steps in the lens differentiation program, including the elimination of organelles to form the core lens organelle-free zone. Other recent studies using ex vivo lens culture …

Machine Learning Approximations To Predict Epigenetic Age Acceleration In Stroke Patients, Isabel Fernández-Pérez, Joan Jiménez-Balado, Uxue Lazcano, Eva Giralt-Steinhauer, Lucía Rey Álvarez, Elisa Cuadrado-Godia, Ana Rodríguez-Campello, Adrià Macias-Gómez, Antoni Suárez-Pérez, Anna Revert-Barberá, Isabel Estragués-Gázquez, Carolina Soriano-Tarraga, Jaume Roquer, Angel Ois, Jordi Jiménez-Conde

2020-Current year OA Pubs

Age acceleration (Age-A) is a useful tool that is able to predict a broad range of health outcomes. It is necessary to determine DNA methylation levels to estimate it, and it is known that Age-A is influenced by environmental, lifestyle, and vascular risk factors (VRF). The aim of this study is to estimate the contribution of these easily measurable factors to Age-A in patients with cerebrovascular disease (CVD), using different machine learning (ML) approximations, and try to find a more accessible model able to predict Age-A. We studied a CVD cohort of 952 patients with information about VRF, lifestyle habits, …

Extending Outbreak Investigation With Machine Learning And Graph Theory: Benefits Of New Tools With Application To A Nosocomial Outbreak Of A Multidrug-Resistant Organism, Andrew Atkinson, Benjamin Ellenberger, Vanja Piezzi, Tanja Kaspar, Luisa Salazar-Vizcaya, Olga Endrich, Alexander B Leichtle, Jonas Marschall

2020-Current year OA Pubs

OBJECTIVE: From January 1, 2018, until July 31, 2020, our hospital network experienced an outbreak of vancomycin-resistant enterococci (VRE). The goal of our study was to improve existing processes by applying machine-learning and graph-theoretical methods to a nosocomial outbreak investigation.

METHODS: We assembled medical records generated during the first 2 years of the outbreak period (January 2018 through December 2019). We identified risk factors for VRE colonization using standard statistical methods, and we extended these with a decision-tree machine-learning approach. We then elicited possible transmission pathways by detecting commonalities between VRE cases using a graph theoretical network analysis approach.

RESULTS: …

Clinical Importance Of Clonal Hematopoiesis In Metastatic Gastrointestinal Tract Cancers, Bill H Diplas, Kelly Bolton, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Clonal hematopoiesis (CH) has been associated with development of atherosclerosis and leukemia and worse survival among patients with cancer; however, the association with cancer therapy efficacy, in particular immune checkpoint blockade (ICB), and toxicity has not yet been established. Given the widespread use of ICB and the critical role hematopoietic stem cell-derived lymphocytes play in mediating antitumor responses, CH may be associated with therapeutic efficacy and hematologic toxicity.

OBJECTIVE: To determine the association between CH and outcomes, hematologic toxicity, and therapeutic efficacy in patients with metastatic gastrointestinal tract cancers being treated with systemic therapy, both in the first-line metastatic …

Fixed-Dose Combination Therapy-Based Protocol Compared With Free Pill Combination Protocol: Results Of A Cluster Randomized Trial, Olutobi A Sanuade, Mark D Huffman, Et Al.

2020-Current year OA Pubs

Fixed-dose combination (FDC) therapy is recommended for hypertension management in Nigeria based on randomized trials at the individual level. This cluster-randomized trial evaluates effectiveness and safety of a treatment protocol that used two-drug FDC therapy as the second and third steps for hypertension control compared with a protocol that used free pill combinations. From January 2021 to June 2021, 60 primary healthcare centers in the Federal Capital Territory of Nigeria were randomized to a protocol using FDC therapy as second and third steps compared with a protocol that used the same medications in free pill combination therapy for these steps. …

Modulation Of Trpv4 Protects Against Degeneration Induced By Sustained Loading And Promotes Matrix Synthesis In The Intervertebral Disc, Garrett W D Easson, Alireza Savadipour, Akila Anandarajah, Leanne E Iannucci, Spencer P Lake, Farshid Guilak, Simon Y Tang

2020-Current year OA Pubs

While it is well known that mechanical signals can either promote or disrupt intervertebral disc (IVD) homeostasis, the molecular mechanisms for transducing mechanical stimuli are not fully understood. The transient receptor potential vanilloid 4 (TRPV4) ion channel activated in isolated IVD cells initiates extracellular matrix (ECM) gene expression, while TRPV4 ablation reduces cytokine production in response to circumferential stretching. However, the role of TRPV4 on ECM maintenance during tissue-level mechanical loading remains unknown. Using an organ culture model, we modulated TRPV4 function over both short- (hours) and long-term (days) and evaluated the IVDs' response. Activating TRPV4 with the agonist GSK101 …

Lgmdd1 Natural History And Phenotypic Spectrum: Implications For Clinical Trials, Andrew R Findlay, Sarah E Robinson, Stephanie Poelker, Michelle Seiffert, Rocio Bengoechea, Conrad C Weihl

2020-Current year OA Pubs

OBJECTIVE: To delineate the full phenotypic spectrum and characterize the natural history of limb girdle muscular dystrophy type D1 (LGMDD1).

METHODS: We extracted age at clinical events of interest contributing to LGMDD1 disease burden via a systematic literature and chart review. Manual muscle testing and quantitative dynamometry data were used to estimate annualized rates of change. We also conducted a cross-sectional observational study using previously validated patient-reported outcome assessments (ACTIVLIM, PROMIS-57) and a new LGMDD1 questionnaire. Some individuals underwent repeat ACTIVLIM and LGMDD1 questionnaire assessments at 1.5 and 2.5 years.

RESULTS: A total of 122 LGMDD1 patients were included from …

An Attention Residual U-Net With Differential Preprocessing And Geometric Postprocessing: Learning How To Segment Vasculature Including Intracranial Aneurysms, Nan Mu, Zonghan Lyu, Mostafa Rezaeitaleshmahalleh, Jinshan Tang, Jingfeng Jiang

Michigan Tech Publications, Part 1

Objective

Intracranial aneurysms (IA) are lethal, with high morbidity and mortality rates. Reliable, rapid, and accurate segmentation of IAs and their adjacent vasculature from medical imaging data is important to improve the clinical management of patients with IAs. However, due to the blurred boundaries and complex structure of IAs and overlapping with brain tissue or other cerebral arteries, image segmentation of IAs remains challenging. This study aimed to develop an attention residual U-Net (ARU-Net) architecture with differential preprocessing and geometric postprocessing for automatic segmentation of IAs and their adjacent arteries in conjunction with 3D rotational angiography (3DRA) images.

Methods

The …

Forest Ecosystem Properties Emerge From Interactions Of Structure And Disturbance, J. Christina Mitchell, Daniel M. Kashian, Xiongwen Chen, Stella Cousins, David J. Flaspohler, Daniel S. Gruner, Jeremy S. Johnson, Thilina D. Surasinghe, Jenny Zambrano, Brian Buma

Michigan Tech Publications, Part 1

Forest structural diversity and its spatiotemporal variability are constrained by environmental and biological factors, including species pools, climate, land-use history, and legacies of disturbance regimes. These factors influence forest responses to disturbances and their interactions with structural diversity, potentially creating structurally mediated emergent properties at local to continental spatial scales and over evolutionary time. Here, we present a conceptual framework for exploring the emergent properties that arise from interactions between forest structural diversity and disturbances. We synthesize and present definitions for key terms, including emergent property, disturbance, and resilience, and highlight various types and examples of emergent properties, such as …

Do We Need Patient-Specific Qa For Adaptively Generated Plans? Retrospective Evaluation Of Delivered Online Adaptive Treatment Plans On Varian Ethos, Xiaodong Zhao, Dennis N Stanley, Carlos E Cardenas, Joseph Harms, Richard A Popple

2020-Current year OA Pubs

BACKGROUND: The clinical introduction of dedicated treatment units for online adaptive radiation therapy (OART) has led to widespread adoption of daily adaptive radiotherapy. OART allows for rapid generation of treatment plans using daily patient anatomy, potentially leading to reduction of treatment margins and increased normal tissue sparing. However, the OART workflow does not allow for measurement of patient-specific quality assurance (PSQA) during treatment delivery sessions and instead relies on secondary dose calculations for verification of adapted plans. It remains unknown if independent dose verification is a sufficient surrogate for PSQA measurements.

PURPOSE: To evaluate the plan quality of previously treated …

Gender Inequality Against Women Fishers In Indonesia, Ani Purwanti, Dyah Wijaningsih, Muh. Afif Mahfud, Aga Natalis

Indonesia Law Review

This study explores whether or not Law No. 7 of 2016 for the Protection and Empowerment of Fishermen, Fish Cultivators, and Salt Farmers discriminates against women. This law supports small fishermen since it requires the government to provide them with financial stability through harvest season output guarantees. On the other hand, we discovered that Law No. 7 of 2016, about the Protection and Empowerment of Fishermen, Fish Cultivators, and Salt Farmers, has discriminatory consequences damaging the welfare of female fishermen. Because of sociological and cultural bias, female fishermen are the most neglected segment in the fishing sector. This is in …

Kasus Wang Renshu: Sebuah Kegagalan Diplomasi Rrc Terhadap Indonesia, Tuty Enoch Muas

Paradigma: Jurnal Kajian Budaya

The Chinese-Indonesian relations in 1951 was in tension due the actions of Ambassador Wang Renshu. As China was not favored in the international arena for its communist stand, the Chinese citizens in Indonesia became important factor in the relations between China and Indonesia where they were divided into taking side with either the communists or the capitalists. Wang Renshu, a senior member in the China Communist Party, has recruited between six and seven hundred thousand Indonesians of Chinese ancestry to adopt Chinese citizenship, of which it became a threat to the Chinese-Indonesian diplomatic relations. The withdrawal of Ambassador Wang Renshu …

Administrative Appeal Decision - Young, Scott (2022-11-14)

Parole Administrative Appeal Decisions

No abstract provided.

Administrative Appeal Decision - Donis, Enrico (2022-07-18)

Parole Administrative Appeal Decisions

No abstract provided.

Decision In Art. 78 Proceeding - Donis, Enrico (2022-11-30)

Decisions in Art. 78 Proceedings

No abstract provided.

Slamdance Film Festival 2023 Introduction, William L. Blizek

Journal of Religion & Film

Introduction to the 2023 Slamdance Film Festival

Slide List, Sui-Kang Zhao 赵穗康

Zhou Documents

This is a brief description of the artist's fifteen slides. The slides' names, date of shooting, way of being perceived, type of installation involved, material, size are included. Some of the descriptions also include the background information of the work. (He Zhang 25')

Improved Process For The Preparation Of (±) 4-Amino-5-Hexenoic Acid, Msn Laboratories Private Limited, R&D Center; Srinivasan Thirumalai Rajan; M. Kishore; M. Ramakrishna; Jillepalli Suresh

Defensive Publications Series

Abstract:

The present invention relates to an improved process for the preparation of (±) 4-amino-5-hexenoic acid, represented by the following structural formula.

Formula-1

High Precision Programmable Delay In Networking Switches, N/A

Defensive Publications Series

Fairness in computer networks used in application domains such as financial markets, prediction markets, etc., can be achieved by ensuring that all participants receive the same multicast information at the same time. However, in practice, due to factors such as differing processing delays at network nodes, differing optical fiber lengths, etc., some participants may receive data sooner than others. This disclosure describes techniques to reduce timing variance and unfairness in multicast networks. Since multicasting works by replicating information to destination nodes, the replication engine at a node of a given network layer is programmed to delay retransmission of information received …

Irewards, Mrudul Uchil, Shakti Nilesh

Defensive Publications Series

The present disclosure relates to providing a single platform (107) to communicate offers/promotions to users (101). The platform receives payment cards details and associated issuer information from a user (101). The platform further receives information related to at least one merchant (105) and favorite brand of the user (101). The information related to the merchant or brand may be a name or an identity number. The platform (107) uses machine learning and/or data analytics and dynamically fetches current offers/promotions associated with the cards that can be availed at the at least one merchant (105) and favorite brand of the user …

Method And System For True Random Number Generation Using Brownian Motion., Gokul Anand Manimaran

Defensive Publications Series

The present disclosure relates to a method and system for generation of true random numbers using Brownian motion without any external inputs. The method creates true random numbers utilizing the random movement of colloidal particles in the colloidal solution. Rotor mechanism used in mechanical watches and heat from the system are used to introduce kinetic energy into this colloidal solution. The present disclosure generates sequence of true random numbers using either picture or video of the colloidal particles in the colloidal medium holder. Using the picture, the method counts the number of colloidal particles in area of any shape. Using …

Basic Idea Of My Works, Sui-Kang Zhao 赵穗康

Zhou Documents

This is a brief explanation of the artist's creative art approach and the meaning behind. (He Zhang 25')