Digital Commons Network^™

Use Of A Blood Biomarker Test Improves Economic Utility In The Evaluation Of Older Patients Presenting With Cognitive Impairment, William J Canestaro, Randall J Bateman, David M Holtzman, Mark Monane, Joel B Braunstein

2020-Current year OA Pubs

More than 16 million Americans living with cognitive impairment warrant a diagnostic evaluation to determine the cause of this disorder. The recent availability of disease-modifying therapies for Alzheimer's disease (AD) is expected to significantly drive demand for such diagnostic testing. Accurate, accessible, and affordable methods are needed. Blood biomarkers (BBMs) offer advantages over usual care amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in these regards. This study used a budget impact model to assess the economic utility of the PrecivityAD

Infectious Diseases Physician Management Of Cryptococcal Meningitis In North America-Is Single High-Dose Liposomal Amphotericin B Being Used?, Nathan C Bahr, Susan E Beekmann, Philip M Polgreen, Jeremey B Walker, Andrej Spec, David R Boulware, John W Baddley

2020-Current year OA Pubs

BACKGROUND: Several recent randomized trials have been conducted in resource-limited settings for cryptococcal meningitis that have rapidly innovated international guidelines. The 2010 Infectious Diseases Society of America (IDSA) cryptococcal meningitis guideline has not been updated with recent trials. The 2022 AMBITION-cm trial found that a single 10-mg/kg dose of liposomal amphotericin B plus daily flucytosine and fluconazole for 2 weeks was noninferior to 1 week of amphotericin B deoxycholate with flucytosine. It is unknown whether physicians in high-resource settings are using this regimen or more traditional regimens.

METHODS: We developed an electronic survey in June 2023 to better understand whether …

Shared Vision For Improving Outcomes For Serious Fungal Diseases: Report Of A Patient, Caregiver, And Clinician Summit, Rob Purdie, Lisa A Tushla, Jonathan Ferretti, Gonzalo Kiko Castro, Ricky Watson, Thomas Davis, Brianna Raborg, Patrick B Mazi, Angela Stroman, Carolynn Thomas Jones, Thomas J Walsh, Tom M Chiller, Peter G Pappas, John Meyer, Andrej Spec

2020-Current year OA Pubs

BACKGROUND: Recently, increasing focus on patient input into research and healthcare improvements has fostered expanded patient-centered advocacy efforts. This first pan-fungal disease summit, part of the MYCology Advocacy, Research, & Education effort, brought together patients, caregivers, and mycology experts to better document patient experiences with invasive fungal disease (IFD) and establish priorities for mycology education, advocacy, and research.

METHODS: Patients who had suffered from IFD, their caregivers, clinicians, industry representatives, government officials, and patient advocacy professionals were invited. Patients and caregivers shared their stories and struggles with IFD. Breakout sessions separated mycology experts from patients and caregivers for further discussions …

The First Reported Case Of Treating The Ultra-Central Thorax With Cone Beam Computed Tomography-Guided Stereotactic Adaptive Radiotherapy (Ct-Star), Stephanie Zhao, Robbie Beckert, Xiaodong Zhao, Eric Laugeman, Clifford G. Robinson, Gregory Vlacich, Pamela P. Samson, Joshua P. Schiff

2020-Current year OA Pubs

Stereotactic body radiotherapy (SBRT) to the central and ultra-central thorax is associated with infrequent but potentially serious adverse events. Adaptive SBRT, which provides more precise treatment planning and inter-fraction motion management, may allow the delivery of ablative doses to ultra-central tumors with effective local control and improved toxicity profiles. Herein, we describe the first reported case of cone beam computed tomography (CBCT)-guided stereotactic adaptive radiotherapy (CT-STAR) in the treatment of ultra-central non-small cell lung cancer (NSCLC) in a prospective clinical trial (NCT05785845). An 80-year-old man with radiographically diagnosed early-stage NSCLC presented for definitive management of an enlarging ultra-central lung nodule. …

A Microbiota-Directed Complementary Food Intervention In 12-18-Month-Old Bangladeshi Children Improves Linear Growth, Ishita Mostafa, Matthew C Hibberd, Steven J Hartman, Md Hasan Hafizur Rahman, Mustafa Mahfuz, S M Tafsir Hasan, Per Ashorn, Michael J Barratt, Tahmeed Ahmed, Jeffrey I Gordon

2020-Current year OA Pubs

BACKGROUND: Globally, stunting affects ∼150 million children under five, while wasting affects nearly 50 million. Current interventions have had limited effectiveness in ameliorating long-term sequelae of undernutrition including stunting, cognitive deficits and immune dysfunction. Disrupted development of the gut microbiota has been linked to the pathogenesis of undernutrition, providing potentially new treatment approaches.

METHODS: 124 Bangladeshi children with moderate acute malnutrition (MAM) enrolled (at 12-18 months) in a previously reported 3-month RCT of a microbiota-directed complementary food (MDCF-2) were followed for two years. Weight and length were monitored by anthropometry, the abundances of bacterial strains were assessed by quantifying metagenome-assembled …

Genetic Loci Regulate Sarbecovirus Pathogenesis: A Comparison Across Mice And Humans, Alexandra Schäfer, Laura A Vanblargan, Larissa B Thackray, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Coronavirus (CoV) cause considerable morbidity and mortality in humans and other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) in 2003, Middle East Respiratory CoV (MERS-CoV) in 2012, and SARS-CoV-2 in 2019. Although poorly characterized, natural genetic variation in human and other mammals modulate virus pathogenesis, as reflected by the spectrum of clinical outcomes ranging from asymptomatic infections to lethal disease. Using multiple human epidemic and zoonotic Sarbecoviruses, coupled with murine Collaborative Cross genetic reference populations, we identify several dozen quantitative trait loci that regulate SARS-like group-2B CoV pathogenesis and replication. Under a Chr4 QTL, we …

Safety Of Non-Cuffed Tunneled Central Venous Catheters In Adults With Cystic Fibrosis, Arshan Dehbozorgi, Badr Jandali, Robert Turner, Aaron Rohr, Brandon Custer, Kate Young, Carissa Walter, Lauren Clark, Yanming Li, Deepika Polineni, Joel Mermis

2020-Current year OA Pubs

BACKGROUND: Peripherally inserted central catheters (PICCs) are the most common route of intravenous (I.V.) access for treatment of cystic fibrosis (CF) pulmonary exacerbations, but repeated PICC placement can result in upper extremity peripheral venous stenosis. Once peripheral stenosis develops, a non-cuffed tunneled central venous catheter (NcTCVC) is an alternative route for IV access. While these are regularly used at some CF centers, the safety and complication rate compared to PICCs in adults with CF has not been reported. This study aims to describe the safety of NcTCVCs in adults with CF.

METHODS: A retrospective cohort study was performed at a …

Predictors Of Non-Variceal Hemorrhage In A National Cohort Of Patients With Chronic Liver Disease, Amber Afzal, Preethi Kesavan, Luo Suhong, Brian F Gage, Kevin Korenblat, Martin Schoen, Kristen Sanfilippo

2020-Current year OA Pubs

BACKGROUND: Non-variceal hemorrhage in patients with chronic liver disease (CLD) increases morbidity, mortality, and healthcare costs. There are limited data on risk factors for non-variceal hemorrhage in the CLD population. The aim of this study was to assess the predictive value of various clinical and laboratory parameters for non-variceal hemorrhage in CLD patients.

METHODS: We conducted a retrospective cohort study of US veterans diagnosed with CLD between 2002 and 2018 within the Veterans Health Administration database. We derived candidate variables from existing risk prediction models for hemorrhage, risk calculators for severity of liver disease, Charlson index of prognostic comorbidities, and …

Efficacy And Safety Of A Four-Drug, Quarter-Dose Treatment For Hypertension: The Quartet Usa Randomized Trial, Mark D Huffman, Et Al.

2020-Current year OA Pubs

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome …

Three-Year Outcomes Of Post-Acute Sequelae Of Covid-19, Miao Cai, Yan Xie, Eric J Topol, Ziyad Al-Aly

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC) in many organ systems. Risks of these sequelae have been characterized up to 2 years after infection, but longer-term follow-up is limited. Here we built a cohort of 135,161 people with SARS-CoV-2 infection and 5,206,835 controls from the US Department of Veterans Affairs who were followed for 3 years to estimate risks of death and PASC. Among non-hospitalized individuals, the increased risk of death was no longer present after the first year of infection, and risk of incident PASC declined over the 3 …

Late-Season Influenza Vaccine Effectiveness Against Medically Attended Outpatient Illness, United States, December 2022-April 2023, Jessie R Chung, Stacey L House, Tara Curley, Et Al.

2020-Current year OA Pubs

BACKGROUND: The 2022-23 US influenza season peaked early in fall 2022.

METHODS: Late-season influenza vaccine effectiveness (VE) against outpatient, laboratory-confirmed influenza was calculated among participants of the US Influenza VE Network using a test-negative design.

RESULTS: Of 2561 participants enrolled from December 12, 2022 to April 30, 2023, 91 laboratory-confirmed influenza cases primarily had A(H1N1)pdm09 (6B.1A.5a.2a.1) or A(H3N2) (3C.2a1b.2a.2b). Overall, VE was 30% (95% confidence interval -9%, 54%); low late-season activity precluded estimation for most subgroups.

CONCLUSIONS: 2022-23 late-season outpatient influenza VE was not statistically significant. Genomic characterization may improve the identification of influenza viruses that circulate postinfluenza peak.

Leveraging Digital Media To Promote Youth Mental Health: Flipping The Script On Social Media-Related Risk, Jessica L Hamilton, John Torous, Hannah S Szlyk, Candice Biernesser, Kaylee P Kruzan, Michaeline Jensen, Jazmin Reyes-Portillo, Brian A Primack, Jamie Zelazny, Paul Weigle

2020-Current year OA Pubs

PURPOSE OF REVIEW: Despite growing public concern about the negative impact of digital media for mental health problems, there are key ways in which digital media can be leveraged to prevent such outcomes. This article reviews research exploring the ways that digital media, particularly social media, can be used to prevent negative mental health outcomes and promote youth mental health and well-being.

RECENT FINDINGS: Research indicates that media can be protective against mental health problems and promote mental health by enabling social support and destigmatizing mental illness, especially for youth with limited resources. Media also can be leveraged to identify …

Genome-Wide Association Studies And Mendelian Randomization Analyses Provide Insights Into The Causes Of Early-Onset Colorectal Cancer, R S Laskar, Y Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed < 50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC.

PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR.

RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH …

Versatile Platelets Contribute To Rejuvenation., John M. Perry, Meng Zhao

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Inherited C-Terminal Trex1 Variants Disrupt Homology-Directed Repair To Cause Senescence And Dna Damage Phenotypes In Drosophila, Mice, And Humans, Samuel D Chauvin, Fang R Zhao, W Alexander Stinson, Wei Qian, Prabhakar S Andhey, Maxim N Artyomov, Elisha D O Roberson, Jonathan J Miner, Et Al.

2020-Current year OA Pubs

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3'-5' DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause …

Factitious Disorder Presenting As Sickle Cell Disease: A Case Report, Jeremy W Jacobs, Brenda J Grossman, Et Al.

2020-Current year OA Pubs

No abstract provided.

Bcar4 Expression As A Predictive Biomarker For Endocrine Therapy Resistance In Breast Cancer, Muheng Liao, Jace Webster, Emily M Coonrod, Katherine N Weilbaecher, Christopher A Maher, Nicole M White

2020-Current year OA Pubs

BACKGROUND: Breast cancer, particularly the estrogen receptor positive (ER+) subtype, remains a leading cause of cancer-related death among women. Endocrine therapy is the most effective treatment for ER+ breast cancer; however, the development of resistance presents a significant challenge. This study explored the role of the breast cancer antiestrogen resistance 4 (BCAR4) gene as a potential driver of resistance and a pivotal biomarker in breast cancer.

PATIENTS AND METHODS: The researchers undertook a comprehensive analysis of 1743 patients spanning 6 independent cohorts. They examined the association of BCAR4 expression with patient outcomes across all breast cancer types and the PAM50 …

Proteolysis Of The Pericellular Matrix: Pinpointing The Role And Involvement Of Matrix Metalloproteinases In Early Osteoarthritic Remodeling, Marina Danalache, Felix Umrath, Rosa Riester, Maik Schwitalle, Farshid Guilak, Ulf Krister Hoffmann

2020-Current year OA Pubs

The pericellular matrix (PCM) serves a critical role in signal transduction and mechanoprotection in chondrocytes. Osteoarthritis (OA) leads to a gradual deterioration of the cartilage, marked by a shift in the spatial arrangement of chondrocytes from initially isolated strands to large cell clusters in end-stage degeneration. These changes coincide with progressive enzymatic breakdown of the PCM. This study aims to assess the role and involvement of specific matrix metalloproteinases (MMPs) in PCM degradation during OA. We selected cartilage samples from 148 OA patients based on the predominant spatial chondrocyte patterns. The presence of various MMPs (-1,-2,-3,-7,-8,-9,-10,-12,-13) was identified by multiplexed …

Ascc1 Structures And Bioinformatics Reveal A Novel Helix-Clasp-Helix Rna-Binding Motif Linked To A Two-Histidine Phosphodiesterase, Naga Babu Chinnam, Jennifer M Soll, Nima Mosammaparast, Et Al.

2020-Current year OA Pubs

Activating signal co-integrator complex 1 (ASCC1) acts with ASCC-ALKBH3 complex in alkylation damage responses. ASCC1 uniquely combines two evolutionarily ancient domains: nucleotide-binding K-Homology (KH) (associated with regulating splicing, transcriptional, and translation) and two-histidine phosphodiesterase (PDE; associated with hydrolysis of cyclic nucleotide phosphate bonds). Germline mutations link loss of ASCC1 function to spinal muscular atrophy with congenital bone fractures 2 (SMABF2). Herein analysis of The Cancer Genome Atlas (TCGA) suggests ASCC1 RNA overexpression in certain tumors correlates with poor survival, Signatures 29 and 3 mutations, and genetic instability markers. We determined crystal structures of Alvinella pompejana (Ap) ASCC1 and Human (Hs) …

Spatially Resolved Metabolomic Dataset Of Distinct Human Kidney Anatomic Regions, Haikuo Li, Benjamin D Humphreys

2020-Current year OA Pubs

Cortex, medulla and papilla are three major human kidney anatomic structures and they harbour unique metabolic functions, but the underlying metabolomic profiles are largely unknown at spatial resolution. Here, we generated a spatially resolved metabolomics dataset on human kidney cortex, medulla and papilla tissues dissected from the same donor. Matrix-Assisted Laser Desorption/Ionization-Imaging Mass Spectrometry (MALDI-IMS) was used to detect metabolite species over mass-to-charge ratios of 50 -1500 for each section at a resolution of 10 × 10 µm

Two-Buoy And Single-Buoy Floating Wave Energy Converters: A Numerical Comparison, Demin Li, Xiaochen Dong, Alistair G.L. Borthwick, Sanjay Sharma, Tianyuan Wang, Heao Huang, Hongda Shi

School of Engineering, Computing and Mathematics

A numerical model of two-buoy and single-buoy floating wave energy converters (WECs) is developed based on a modified nonlinear version of WEC-Sim. The model is validated against experimental data from a 1:5 geometric scale model of a two-buoy floating WEC. Nonlinear behavior is primarily attributed to viscous damping and mechanical friction effects. It is found that a modified version of WEC-Sim obtained by correcting the phase of the wave excitation force in the source code provides an accurate representation of a two-buoy WEC operating in either linear or nonlinear mode. An equivalent single-buoy WEC is modeled by locking the two-buoys …

Experimental Investigation Of Mechanical Properties Of Ggbs-Fa-Sf Blended Geopolymer Concrete At Elevated Temperatures, Tan Wang, Min Yu, Hanjie Lin, Dawang Li, Long Yuan Li

School of Engineering, Computing and Mathematics

Geopolymer has excellent mechanical properties at elevated temperatures, but geopolymer concrete may not be so because of the large difference in thermal properties between geopolymer and aggregate which could lead to substantial thermal stresses when they are in a high temperature environment. In this paper we present an experimental investigation on the mechanical properties of GGBS-FA-SF blended geopolymer concrete with and without steel fibres at elevated temperatures. The influences of exposure temperature, coarse aggregate and steel fibre on the failure mode, compressive strength, elastic modulus, peak strain, and ductility of the geopolymer mortar and geopolymer concrete are examined. Based on …

Soil Saturation Limits Early Oak Establishment In Upland Pastures For Restoration Of Atlantic Oak Woodlands, Thomas R. Murphy, Mick E. Hanley, Jon S. Ellis, Paul H. Lunt

School of Geography, Earth and Environmental Sciences

With woodland expansion providing a nature-based solution to help tackle anthropogenic climate change, the persistence and regeneration of fragmented Atlantic oak woodland is a critical feature of the wilding of uplands and conservation of Temperate Rainforests in Western Europe. Predicted shifts in precipitation with climate change are likely to be a major determinant of tree recruitment here, yet our understanding of the threshold effects of high soil moisture on oak establishment is limited, particularly at early-life-history stages when trees are most vulnerable. We address this gap in knowledge by investigating the effect of soil saturation states on; 1) the capacity …

Water Management And Conservation In India Fostering Water Justice: Arguing For Adopting Just Sustainability In Water Governance, Gayathri D Naik Dr, Sanjay Shenoi P

Articles

The water sector is characterised by everyday water injustices where factors like social discrimination, economic disparities, and political preferences influence the determination of water resource access, allocation, and management. The increasing anthropogenic impacts on water resources and consequent threats to sustainability add to the water injustices, often impacting the poorer, socially downtrodden communities that bear the brunt of water scarcity and cannot afford alternatives. The current water governance patterns, prioritising equality over equity, fail to address the issues of water injustices created by social, political, and economic factors in water management and sideline the ecological impacts on water resources. Moving …

Synthesis Of Dyes Sulfamidazole: Characterization, Evaluation, Molecular Docking And Global Descriptors By Density Functional Theory (Dft)., Athra G. Sager, Jawad Kadhim Abaies, Zeena R. Katoof

Karbala International Journal of Modern Science

In the present work, novel azo compounds of sulfamidazole were created via the reaction of diazonium salt of sulfamidazole with several aromatic molecules including (resorcinol, 2-nitro phenol, 3-nitro phenol, and 4-nitro phenol)) (Z1–Z4). The new compounds (Z1-Z4) were identified using FTIR, ¹HNMR techniques, in addition to melting point measurements. The biological activity of compounds (Z1-Z4) was studied against four kinds of bacteria including E. coli, Klebsiella pneumonia, Salmonella, and Staphylococcus aureus. The findings showed that all compounds (Z1-Z4) were active against the examined bacteria. Theoretical studies of the antibacterial ability of the prepared compound against DNA gyrase enzyme …

Session 5: Generative Ai Tort Liability, Mark Chinen

SITIE Symposiums

In Session Five of the SITIE2024 Symposium titled “Generative AI Tort Liability,” Professor Mark Chinen discussed Tort law in relation to artificial intelligence. He began by discussing the emerging harms in software development and then transitioned to generative AI, identifying features relevant to tort liability. Chinen also addressed the actors and parties involved in AI development and use in tort law and explored the broad issues in tort law and generative AI. Focusing on the US context, he discussed harm related to Freedom of Expression and specific torts related to AI harms. Finally, he briefly discussed the European Union's approach …

Cover, Table Of Contents & Masthead, Mariam Antony

Journal of the National Association of Administrative Law Judiciary

No abstract provided.

Job Incidence Numbers In Social Security Disability Claims: A Case Study And Analysis, Kevin Liebkemann

Journal of the National Association of Administrative Law Judiciary

The Social Security Administration (SSA) processes numerous disabled worker applications each year. In adult disability claims, SSA employs a strict five-step sequential disability evaluation to decide whether a person is disabled. Many adult Social Security Disability claimants either win or lose at the fifth and final step, where an SSA adjudicator decides whether there is “a significant number of jobs (in one or more occupations) having requirements which you are able to meet with your physical or mental abilities and vocational qualifications.” This article examines the vocational evidence that SSA uses to decide the significant number of jobs issue. It …

Diabetes Management Of Incarcerated Individuals: Is The Federal Bureau Of Prisons Contributing To Worsening Diabetic Conditions?, Mariam Antony

Journal of the National Association of Administrative Law Judiciary

There are many issues related to noncommunicable disease care in federal prisons, which fall under the management of the U.S. Bureau of Prisons, a federal agency. Although there are many noncommunicable diseases, this comment specifically focuses on diabetes because of its prevalence (how common it is in individuals), especially in incarcerated individuals. Prison and incarceration are not conducive to the management of diabetes because diabetes may not even show symptoms until an individual mismanages the disease for a long time. An individual could first appear normal and then suffer a diabetic emergency, which could lead to consequences like heart attack …

Legal Summaries Of Administrative Law Cases, Keyana Young

Journal of the National Association of Administrative Law Judiciary

No abstract provided.