Digital Commons Network^™

The Post-Transplant Lymphoproliferative Disorders-Metagenomic Shotgun Microbial Sequencing (Ptld-Msms) Study Methods And Protocol, Vikas R. Dharnidharka, Kristine M. Wylie, Todd N. Wylie, Marianna B. Ruzinova, Charles W. Goss, Gregory A. Storch, Neha Mehta-Shah, Derek Byers, Leslie Walther, Lujain Jaza, Hongjie Gu, Mansi Agarwal, Et Al.

2020-Current year OA Pubs

Post-transplant lymphoproliferative disorders (PTLDs) remain a feared complication of transplantation, with significant morbidity and mortality. The oncogenic Epstein-Barr virus (EBV) is a key pathogenic driver in 50%-80% of cases. Numerous prognostic indices, comprising multiple clinical, epidemiological and tumor characteristics, including EBV tumor positivity, do not consistently associate with worse patient survival, suggesting a potential role for EBV genome variants in determining outcome. However, the precision medicine tools for determining if a viral genome variant is pathogenic are very limited compared with human genome variants. Further, targeted studies have not implicated a specific viral etiological agent in EBV-negative PTLD. Using novel …

Evidence Of Human Bourbon Virus Infections, North Carolina, Usa, Diana L Zychowski, Gayan Bamunuarachchi, Scott P Commins, Ross M Boyce, Adrianus C M Boon

2020-Current year OA Pubs

Bourbon virus is a tickborne virus that can cause human disease. Cases have been reported in Kansas, Oklahoma, and Missouri, USA. We identified Bourbon virus-specific neutralizing antibodies in patients from North Carolina. Bourbon virus infections are likely more common than previously thought, highlighting the need for improved diagnostics and surveillance.

Association Between Glucagon-Like Peptide-1 Receptor Agonist Use And Progression Of Monoclonal Gammopathy Of Uncertain Significance To Multiple Myeloma Among Patients With Diabetes, Nikhil Grandhi, Lawrence Liu, Mei Wang, Theodore Thomas, Martin Schoen, Kristen Sanfilippo, Feng Gao, Graham A Colditz, Kenneth R Carson, Murali Janakiram, Su-Hsin Chang

2020-Current year OA Pubs

BACKGROUND: In patients with diabetes and monoclonal gammopathy of uncertain significance (MGUS), the impact of glucagon-like peptide-1 (GLP-1) receptor agonists on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1 receptor agonist use in the progression of MGUS to multiple myeloma in patients with diabetes.

METHODS: This is a population-based cohort study of veterans diagnosed with MGUS from 2006 to 2021 with a prior diagnosis of diabetes. A validated natural language processing algorithm was used to confirm MGUS and progression to multiple myeloma. We performed 1:2 matching for individuals with and without GLP-1 receptor …

A Case Report Of An Unprovoked Neonatal Pulmonary Embolism: Management Strategies And Cardiopulmonary Complications, Aashana Dhruva Cowan, Ezinwanne Rosemary Emelue, George Spyropoulos, Mehul Thakkar, Jorge Di Paola, Andrew Glatz, Edon J Rabinowitz

2020-Current year OA Pubs

BACKGROUND: Neonatal pulmonary embolism is a rare occurrence, especially when idiopathic, instead occurring in patients with identifiable risk factors including severe dehydration, presence or history of a central venous line, or identifiable genetic causes. Given the rarity of paediatric and neonatal pulmonary emboli, few guidelines exist to support the clinician in both the initial resuscitation and ongoing management of the critically ill patient with pulmonary emboli.

CASE SUMMARY: We present a 5-day-old female with unprovoked massive pulmonary embolism and associated haemodynamic compromise. She presented with central cyanosis and weak respiratory effort with hypoxaemia, persistent tachycardia, and hypotension despite initial fluid …

Effect Of Surgical Fixation Timing On In-Hospital Mortality And Morbidity Of Distal Femur Fractures, Joseph T Gutbrod, Dustin Stwalley, Anna N Miller

2020-Current year OA Pubs

INTRODUCTION: The literature lacks a large-scale study investigating the effect of surgical fixation timing on early mortality and morbidity outcomes in distal femur fractures. The aims of this study were to determine the effect of fixation timing on in-hospital mortality and morbidity outcomes for operatively treated distal femur fractures retrospectively using large database data.

METHODS: This study is a retrospective analysis using data from the National Trauma Data Bank. Patients were stratified into a fragility cohort (age ≥ 60, ISS < 16) and polytrauma cohort (age < 60, ISS ≥16), with both cohorts analyzed separately. Within each cohort, patients were split into three fixation timing groups: within 24 h, between 24 and 48 h, and greater than 48 h from presentation to the hospital. Fixation-timing groups were compared based on the primary outcome of in-hospital mortality rate. Secondary outcomes included hospital length of stay (LOS), ICU length of stay (ICU LOS), days on a ventilator, and complications.

RESULTS: The fragility and polytrauma cohorts included 22,045 and 5,905 patients, respectively. The in-hospital mortality rate was 1.23 % in …

Hook Of Hamate Regrowth After Surgical Excision: A Report Of Two Cases, Michele Christy, Charles A Goldfarb, Douglas Carlan

2020-Current year OA Pubs

Two high-level baseball players sustained a hook of hamate fracture while batting and were treated with excision of the fragment. Both players returned to play, and both had repeat fractures through a regenerated hook. This phenomenon of hook of hamate regeneration has not been well described in the literature. In conclusion, hook of hamate regeneration can occur after fracture fragment excision. The incidence and risk of this sequela as well as its association with surgical technique is uncertain.

Influence Of Physical Activity Measurement On The Association Between Life's Essential 8 And Incident Cardiovascular Disease In Older Women, Eric T Hyde, Steve Nguyen, Michael J Lamonte, Chongzhi Di, John Bellettiere, Lesley F Tinker, Randi E Foraker, Hilary A Tindle, Marcia L Stefanick, Andrea Z Lacroix

2020-Current year OA Pubs

OBJECTIVE: The American Heart Association's Life's Essential 8 (LE8) metric includes self-reported physical activity as one of the metrics for assessing cardiovascular health. Self-reported physical activity is prone to misclassification, whereas accelerometer measures are less biased. We examined associations of LE8 and incident cardiovascular disease (CVD) using self-reported and accelerometer-measured physical activity.

METHODS: Participants in the Women's Health Initiative (WHI) Objective Physical Activity and Cardiovascular Health Study (n = 4,243; mean age = 79 ± 7 years) with no CVD history completed the WHI physical activity questionnaire and the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire prior to …

Impact Of Artificial Intelligence-Based Autosegmentation Of Organs At Risk In Low- And Middle-Income Countries, Solomon Kibudde, Awusi Kavuma, Yao Hao, Tianyu Zhao, Hiram Gay, Jacaranda Van Rheenen, Pavan Mukesh Jhaveri, Minjmaa Minjgee, Enkhsetseg Vanchinbazar, Urdenekhuu Nansalmaa, Baozhou Sun

2020-Current year OA Pubs

PURPOSE: Radiation therapy (RT) processes require significant human resources and expertise, creating a barrier to rapid RT deployment in low- and middle-income countries (LMICs). Accurate segmentation of tumor targets and organs at risk (OARs) is crucial for optimal RT. This study assessed the impact of artificial intelligence (AI)-based autosegmentation of OARs in 2 LMICs.

METHODS AND MATERIALS: Ten patients, comprising 5 head and neck (HN) cancer patients and 5 prostate cancer patients, were randomly selected. Planning computed tomography images were subjected to autosegmentation using an Food and Drug Administration-approved AI software tool and manual segmentation by experienced radiation oncologists from …

Assessing Radiology And Radiation Therapy Needs For Cancer Care In Low-And-Middle-Income Countries: Insight From A Global Survey Of Departmental And Institutional Leaders, Stephanie A Parker, Yao Hao, Et Al.

2020-Current year OA Pubs

PURPOSE: The global cancer burden and mortality rates are increasing, with significant disparities in access to care in low- and middle-income countries (LMICs). This study aimed to identify radiology and radiation therapy needs in LMICs from the perspective of departmental and institutional leaders.

METHODS AND MATERIALS: A survey was developed and conducted by the American Association of Physicists in Medicine Global Needs Assessment Committee and the American Association of Physicists in Medicine International Council. The survey, organized into 5 sections (Introduction, Infrastructure Needs, Education Needs, Research Needs, and General Information), was open to respondents from March 1, to August 16, …

Relationship Between Mri Brain-Age Heterogeneity, Cognition, Genetics And Alzheimer's Disease Neuropathology, Mathilde Antoniades, Pamela Lamontagne, Tammie Benzinger, Daniel S Marcus, John C Morris, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD).

METHODS: Functional and structural brain age measures were obtained for resting-state functional MRI and structural MRI, respectively, in 3460 cognitively normal individuals across an age …

Tocilizumab Prophylaxis Following Axicabtagene Ciloleucel In Relapsed Or Refractory Large B-Cell Lymphoma, Frederick L Locke, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Most patients treated with axi-cel experience cytokine release syndrome (CRS) and/or adverse neurologic events (NEs). To explore potential approaches for reducing CAR T-cell-related toxicities with axi-cel, several safety expansion cohorts were added to the pivotal ZUMA-1 trial. ZUMA-1 Cohort 3 was an exploratory safety cohort that investigated the use of the IL-6 receptor-blocking antibody tocilizumab and anticonvulsant levetiracetam as prophylaxis against CRS and NEs in patients treated with axi-cel. Patients with R/R LBCL were enrolled in Cohort …

Iglon5 Frequency In Idiopathic Rem Sleep Behavior Disorder: A Multicenter Study, Ronald Postuma, Jennifer Mcleland, Albert A. Davis, Yo-El S. Ju, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.

METHODS: Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma …

Impact Of Self-Reported Race On Villalta Scale Postthrombotic Syndrome Scores And Correlation With Venous Disease-Specific Quality Of Life: An Exploratory Analysis Of The Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis Trial, James Shih, Chu-Shu Gu, Suresh Vedantham, John Kaufman, Susan R Kahn

2020-Current year OA Pubs

BACKGROUND: The Villalta Scale (VS) to diagnose postthrombotic syndrome (PTS) consists of 5 patient-reported leg symptoms and 6 clinician-rated leg signs. It is unknown how the scale performs across racial groups.

OBJECTIVES: Our study explored if there were differences in VS scores, particularly clinician-rated signs components, according to self-reported race.

METHODS: Exploratory analysis of the ATTRACT trial, a randomized controlled trial conducted at 56 US sites that investigated pharmacomechanical catheter-directed thrombolysis to prevent PTS after proximal deep vein thrombosis (DVT). At the 6-month visit after randomization, we compared self-reported Black (n = 123) and White (n = 541) participants for …

Efficacy, Safety, And Quality Of Life 4 Years After Valoctocogene Roxaparvovec Gene Transfer For Severe Hemophilia A In The Phase 3 Gener8-1 Trial, Andrew D Leavitt, Elaine Majerus, Et Al.

2020-Current year OA Pubs

BACKGROUND: Valoctocogene roxaparvovec, an adeno-associated virus-mediated gene therapy for severe hemophilia A, enables endogenous factor (F)VIII expression and provides bleed protection.

OBJECTIVES: Determine valoctocogene roxaparvovec durability, efficacy, and safety 4 years after treatment.

METHODS: In the phase 3 GENEr8-1 trial, 134 adult male persons with severe hemophilia A without inhibitors and previously using FVIII prophylaxis received a 6 × 10

RESULTS: Median follow-up was 214.3 weeks; 2 participants discontinued since the previous data cutoff. Declines from baseline in mean treated annualized bleed rate (-82.6%;

CONCLUSION: Valoctocogene roxaparvovec provides persistent FVIII expression, hemostatic control, and health-related quality of life improvements with …

Fusobacterium Nucleatum Abundance Is Associated With Cachexia In Colorectal Cancer Patients: The Colocare Study, Mmadili N Ilozumba, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and indicates poor prognosis. The impact of Fusobacterium nucleatum (Fn), a microbial risk factor for colorectal cancer (CRC), on the development of cachexia in CRC has not been established.

METHODS: We evaluated the association between Fn abundance in pre-surgical stool samples and onset of cachexia at 6 months post-surgery in n = 87 patients with stages I-III CRC in the ColoCare Study.

RESULTS: High fecal Fn abundance compared to negative/low fecal Fn abundance was associated with 4-fold increased risk of cachexia onset at 6 months post-surgery (OR = 4.82, 95% …

Evaluation Of Combat Harmonization For Reducing Across-Tracer Differences In Regional Amyloid Pet Analyses, Braden Yang, Tom Earnest, Sayantan Kumar, Deydeep Kothapalli, Tammie Benzinger, Brian Gordon, Aristeidis Sotiras

2020-Current year OA Pubs

Differences in amyloid positron emission tomography (PET) radiotracer pharmacokinetics and binding properties lead to discrepancies in amyloid-β uptake estimates. Harmonization of tracer-specific biases is crucial for optimal performance of downstream tasks. Here, we investigated the efficacy of ComBat, a data-driven harmonization model, for reducing tracer-specific biases in regional amyloid PET measurements from [

Effectiveness Of Original Monovalent And Bivalent Covid-19 Vaccines Against Covid-19-Associated Hospitalization And Severe In-Hospital Outcomes Among Adults In The United States, September 2022-August 2023, Jennifer Decuir, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes.

METHODS: During September 8, 2022 to August 31, 2023, adults aged ≥ 18 years hospitalized with COVID-19-like illness were enrolled at 26 hospitals in 20 US states. Using a test-negative case-control design, we estimated vaccine effectiveness (VE) with multivariable logistic regression adjusted for age, sex, race/ethnicity, admission date, and geographic region.

RESULTS: Among 7028 patients, 2924 (41.6%) were …

A Finite Element Model For Biomechanical Characterization Of Ex Vivo Peripheral Nerve Dysfunction During Stretch, Nicholas C Vasas, Adam M Forrest, Nathaniel A Meyers, Michael B Christensen, Jenny L Pierce, Sidney M Kaufmann, Kimberly B Lanaghen, Randal C Paniello, Julie M Barkmeier-Kraemer, Jonathan P Vande Geest

2020-Current year OA Pubs

Peripheral nerve damage can cause debilitating symptoms ranging from numbness and pain to sensory loss and atrophy. To uncover the underlying mechanisms of peripheral nerve injury, our research aims to develop a relationship between biomechanical peripheral nerve damage and function through finite element modeling. A noncontact, ex vivo electrophysiology chamber, capable of axially stretching explanted nerves while recording electrical signals, was used to investigate peripheral nerve injury. Successive stretch trials were run on eight sciatic nerves (four females and four males) excised from Sprague-Dawley rats. Nerves were stretched until 50% compound action potential (CAP) amplitude reduction was obtained. A constitutive …

A Site-Wise Reliability Analysis Of The Abcd Diffusion Fractional Anisotropy And Cortical Thickness: Impact Of Scanner Platforms, Yezhi Pan, L Elliot Hong, Ashley Acheson, Paul M Thompson, Neda Jahanshad, Alyssa H Zhu, Jiaao Yu, Chixiang Chen, Tianzhou Ma, Ho-Ling Liu, Jelle Veraart, Els Fieremans, Nicole R Karcher, Peter Kochunov, Shuo Chen

2020-Current year OA Pubs

The Adolescent Brain and Cognitive Development (ABCD) project is the largest study of adolescent brain development. ABCD longitudinally tracks 11,868 participants aged 9-10 years from 21 sites using standardized protocols for multi-site MRI data collection and analysis. While the multi-site and multi-scanner study design enhances the robustness and generalizability of analysis results, it may also introduce nonbiological variances including scanner-related variations, subject motion, and deviations from protocols. ABCD imaging data were collected biennially within a period of ongoing maturation in cortical thickness and integrity of cerebral white matter. These changes can bias the classical test-retest methodologies, such as intraclass correlation …

Safety Evaluations Of Rapamycin Perfluorocarbon Nanoparticles In Ovarian Tumor-Bearing Mice, Qingyu Zhou, John C Harding, Ping Fan, Ivan Spasojevic, Attila Kovacs, Antonina Akk, Adam Mitchell, Luke E Springer, Joseph P Gaut, Daniel A Rauch, Samuel A Wickline, Christine T N Pham, Katherine Fuh, Hua Pan

2020-Current year OA Pubs

Nanomedicine holds great potential for revolutionizing medical treatment. Ongoing research and advancements in nanotechnology are continuously expanding the possibilities, promising significant advancements in healthcare. To fully harness the potential of nanotechnology in medical applications, it is crucial to conduct safety evaluations for the nanomedicines that offer effective benefits in the preclinical stage. Our recent efficacy studies indicated that rapamycin perfluorocarbon (PFC) nanoparticles showed promise in mitigating cisplatin-induced acute kidney injury (AKI). As cisplatin is routinely administered to ovarian cancer patients as their first-line chemotherapy, in this study, we focused on evaluating the safety of rapamycin PFC nanoparticles in mice bearing …

Csf Proteomics Identifies Early Changes In Autosomal Dominant Alzheimer's Disease, Yuanyuan Shen, Jigyasha Timsina, Gyujin Heo, Aleksandra Beric, Muhammad Ali, Ciyang Wang, Chengran Yang, Yueyao Wang, Daniel Western, Menghan Liu, Priyanka Gorijala, John Budde, Anh Do, Haiyan Liu, Brian Gordon, Jorge J Llibre-Guerra, Nelly Joseph-Mathurin, Richard J Perrin, Dario Maschi, Eric Mcdade, John C Morris, Randall J Bateman, Laura Ibanez, Yun Ju Sung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

In this high-throughput proteomic study of autosomal dominant Alzheimer's disease (ADAD), we sought to identify early biomarkers in cerebrospinal fluid (CSF) for disease monitoring and treatment strategies. We examined CSF proteins in 286 mutation carriers (MCs) and 177 non-carriers (NCs). The developed multi-layer regression model distinguished proteins with different pseudo-trajectories between these groups. We validated our findings with independent ADAD as well as sporadic AD datasets and employed machine learning to develop and validate predictive models. Our study identified 137 proteins with distinct trajectories between MCs and NCs, including eight that changed before traditional AD biomarkers. These proteins are grouped …

Association Between Patient Medications And Postoperative Outcomes In Early-Stage Non-Small Cell Lung Cancer, Steven Tohmasi, Daniel B Eaton, Nikki E. Rossetti, Carley Pickett, Brendan T. Heiden, Yan Yan, Theodore S. Thomas, Deepika Gopukumar, Mayank R. Patel, Ana A. Baumann, Daniel Kreisel, Ruben G. Nava, Whitney S. Brandt, Bryan F. Meyers, Benjamin D. Kozower, Su-Hsin Chang, Varun Puri, Martin W. Schoen

2020-Current year OA Pubs

BACKGROUND: Currently, there is no consensus on how to comprehensively assess comorbidities in lung cancer patients in the clinical setting. Prescription medications may be a preferred comorbidity assessment tool and provide a simple mechanism for predicting postoperative outcomes for lung cancer. We examined the relationship between prescription medications and postoperative outcomes for early-stage non-small cell lung cancer (NSCLC).

METHODS: We conducted a retrospective cohort study of patients with clinical stage I NSCLC who underwent surgical resection in the Veterans Health Administration (VHA) between 10/01/2006 and 09/30/2016. Details of all outpatient prescriptions filled by patients within the VHA system from 1-year …

Documenting Adaptations To An Evidence-Based Intervention In 58 Resource-Variable Pediatric Oncology Hospitals Across Implementation Phases, Alejandra Catalina Quesada-Stoner, Sayeda Islam, Sara Malone, Kim Prewitt, Bobbi J Carothers, Douglas A Luke, Virginia R R Mckay, Et Al.

2020-Current year OA Pubs

BACKGROUND: Adaptation of evidence-based interventions (EBIs) often occurs when implemented in new local contexts and settings. It is unclear, however, during which phase of implementation adaptations are most frequently made and how these changes may impact the fidelity, effectiveness, and sustainability of the EBI. Pediatric Early Warning Systems (PEWS) are EBIs for early identification of deterioration in hospitalized children with cancer. This study evaluates adaptations of PEWS made among resource-variable pediatric oncology hospitals in Latin America implementing and sustaining PEWS.

METHODS: We conducted a cross-sectional survey among pediatric oncology centers participating in Proyecto Escala de Valoración de Alerta Temprana (EVAT), …

Examining The Impact Of The Quartet Usa Trial Using The Translational Science Benefits Model, Guhan Iyer, Danielle Lazar, Abigail S. Baldridge, Jairo Mejia, Clara K. Chow, Namratha R. Kandula, Olutobi A. Sanuade, Linda Rosul, Jody D. Ciolino, Mark D. Huffman

2020-Current year OA Pubs

No abstract provided.

Tumour Evolution And Microenvironment Interactions In 2d And 3d Space, Chia-Kuei Mo, Jingxian Liu, Siqi Chen, Erik Storrs, Andre Luiz N Targino Da Costa, Andrew Houston, Michael C Wendl, Reyka G Jayasinghe, Michael D Iglesia, John M Herndon, Austin N Southard-Smith, Jacqueline Mudd, Alla Karpova, Andrew Shinkle, S Peter Goedegebuure, Abdurrahman Taha Mousa Ali Abdelzaher, Peng Bo, Lauren Fulghum, Samantha Livingston, Angela Hill, Joseph E Ippolito, Jason M Held, Ian S Hagemann, Eric H Kim, Peter O Bayguinov, Albert H Kim, Mary M Mullen, Kooresh I Shoghi, Melissa A Reimers, Cody Weimholt, Liang-I Kang, Sidharth V Puram, Deborah J Veis, Russell Pachynski, Katherine C Fuh, Milan G Chheda, William E Gillanders, Ryan C Fields, Feng Chen, Li Ding, Et Al.

2020-Current year OA Pubs

To study the spatial interactions among cancer and non-cancer cells

Mutational Scanning Of Crx Classifies Clinical Variants And Reveals Biochemical Properties Of The Transcriptional Effector Domain, James L Shepherdson, David M Granas, Jie Li, Zara Shariff, Stephen P Plassmeyer, Alex S Holehouse, Michael A White, Barak A Cohen

2020-Current year OA Pubs

The transcription factor (TF) cone-rod homeobox (CRX) is essential for the differentiation and maintenance of photoreceptor cell identity. Several human

State Of The Art Of Mobile Health Technologies Use In Clinical Arrhythmia Care, Arun R Sridhar, Jennifer N A Silva, Et Al.

2020-Current year OA Pubs

The rapid growth in consumer-facing mobile and sensor technologies has created tremendous opportunities for patient-driven personalized health management. The diagnosis and management of cardiac arrhythmias are particularly well suited to benefit from these easily accessible consumer health technologies. In particular, smartphone-based and wrist-worn wearable electrocardiogram (ECG) and photoplethysmography (PPG) technology can facilitate relatively inexpensive, long-term rhythm monitoring. Here we review the practical utility of the currently available and emerging mobile health technologies relevant to cardiac arrhythmia care. We discuss the applications of these tools, which vary with respect to diagnostic performance, target populations, and indications. We also highlight that requirements …

Engineered Cas9 Variants Bypass Keap1-Mediated Degradation In Human Cells And Enhance Epigenome Editing Efficiency, Jianfeng Chen, Siyuan Su, Adrian Pickar-Oliver, Anna M Chiarella, Quentin Hahn, Dennis Goldfarb, Erica W Cloer, George W Small, Smaran Sivashankar, Dale A Ramsden, Michael B Major, Nathaniel A Hathaway, Charles A Gersbach, Pengda Liu

2020-Current year OA Pubs

As a potent and convenient genome-editing tool, Cas9 has been widely used in biomedical research and evaluated in treating human diseases. Numerous engineered variants of Cas9, dCas9 and other related prokaryotic endonucleases have been identified. However, as these bacterial enzymes are not naturally present in mammalian cells, whether and how bacterial Cas9 proteins are recognized and regulated by mammalian hosts remain poorly understood. Here, we identify Keap1 as a mammalian endogenous E3 ligase that targets Cas9/dCas9/Fanzor for ubiquitination and degradation in an 'ETGE'-like degron-dependent manner. Cas9-'ETGE'-like degron mutants evading Keap1 recognition display enhanced gene editing ability in cells. dCas9-'ETGE'-like degron …

Partial Wrapping Of Single-Stranded Dna By Replication Protein A And Modulation Through Phosphorylation, Rahul Chadda, Vikas Kaushik, Iram Munir Ahmad, Jaigeeth Deveryshetty, Alex S Holehouse, Snorri Th Sigurdsson, Gargi Biswas, Yaakov Levy, Brian Bothner, Richard B Cooley, Ryan A Mehl, Reza Dastvan, Sofia Origanti, Edwin Antony

2020-Current year OA Pubs

Single-stranded DNA (ssDNA) intermediates which emerge during DNA metabolic processes are shielded by replication protein A (RPA). RPA binds to ssDNA and acts as a gatekeeper to direct the ssDNA towards downstream DNA metabolic pathways with exceptional specificity. Understanding the mechanistic basis for such RPA-dependent functional specificity requires knowledge of the structural conformation of ssDNA when RPA-bound. Previous studies suggested a stretching of ssDNA by RPA. However, structural investigations uncovered a partial wrapping of ssDNA around RPA. Therefore, to reconcile the models, in this study, we measured the end-to-end distances of free ssDNA and RPA-ssDNA complexes using single-molecule FRET and …

Rezafungin Versus Caspofungin For Patients With Candidaemia Or Invasive Candidiasis In The Intensive Care Unit: Pooled Analyses Of The Restore And Strive Randomised Trials, Patrick M Honoré, Massimo Girardis, Marin Kollef, Oliver A Cornely, George R Thompson Iii, Matteo Bassetti, Alex Soriano, Haihui Huang, Jose Vazquez, Bart Jan Kullberg, Peter G Pappas, Nick Manamley, Taylor Sandison, John Pullman, Saad Nseir

2020-Current year OA Pubs

BACKGROUND: Rezafungin is an echinocandin approved in the US and EU to treat candidaemia and/or invasive candidiasis. This post-hoc, pooled analysis of the Phase 2 STRIVE and Phase 3 ReSTORE trials assessed rezafungin versus caspofungin in patients with candidaemia and/or invasive candidiasis (IC) in the intensive care unit (ICU) at randomisation.

METHODS: STRIVE and ReSTORE were randomised double-blind trials in adults with systemic signs and mycological confirmation of candidaemia and/or IC in blood or a normally sterile site ≤ 96 h before randomisation. Data were pooled for patients in the ICU at randomisation who received intravenous rezafungin (400 mg loading …