Digital Commons Network^™

Leveraging Gpt-4 For Identifying Cancer Phenotypes In Electronic Health Records: A Performance Comparison Between Gpt-4, Gpt-3.5-Turbo, Flan-T5, Llama-3-8b, And Spacy's Rule-Based And Machine Learning-Based Methods, Kriti Bhattarai, Inez Y Oh, Jonathan Moran Sierra, Jonathan Tang, Philip R O Payne, Zach Abrams, Albert M Lai

2020-Current year OA Pubs

OBJECTIVE: Accurately identifying clinical phenotypes from Electronic Health Records (EHRs) provides additional insights into patients' health, especially when such information is unavailable in structured data. This study evaluates the application of OpenAI's Generative Pre-trained Transformer (GPT)-4 model to identify clinical phenotypes from EHR text in non-small cell lung cancer (NSCLC) patients. The goal was to identify disease stages, treatments and progression utilizing GPT-4, and compare its performance against GPT-3.5-turbo, Flan-T5-xl, Flan-T5-xxl, Llama-3-8B, and 2 rule-based and machine learning-based methods, namely, scispaCy and medspaCy.

MATERIALS AND METHODS: Phenotypes such as initial cancer stage, initial treatment, evidence of cancer recurrence, and affected …

Caregiver Wellness After Traumatic Brain Injury (Cg-Well): Protocol For A Randomized Clinical Trial, Natalie Kreitzer, Stephanie Fink, Opeolu Adeoye, Brad Kurowski G, Shari Wade, Heidi Sucharew, Tamilyn Bakas

2020-Current year OA Pubs

INTRODUCTION: After injury, survivors of moderate to severe traumatic brain injury (msTBI) depend on informal family caregivers. Upwards of 77 % of family caregivers experience poor outcomes, such as adverse life changes, poor health-related quality of life, and increased depressive symptoms. Caregivers frequently report minimal support or training to prepare them for their new role. The majority of previously developed caregiver and caregiver/survivor dyad interventions after msTBI focus on providing information to either survivors only, or to long-term caregivers, rather than to the new caregiver. This manuscript describes the protocol of an ongoing randomized control trial, Caregiver Wellness after TBI …

Dcrm 2.0: Multispecialty Practice Recommendations For The Management Of Diabetes, Cardiorenal, And Metabolic Diseases, Yehuda Handelsman, Samuel Klein, Et Al.

2020-Current year OA Pubs

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need …

Evaluating The Interaction Between Hemorrhagic Transformation And Cerebral Edema On Functional Outcome After Ischemic Stroke, Amrit Avula, Quoc Bui, Atul Kumar, Yasheng Chen, Ali Hamzehloo, Julien Cifarelli, Laura Heitsch, Agnieszka Slowik, Daniel Strbian, Jin-Moo Lee, Rajat Dhar

2020-Current year OA Pubs

BACKGROUND: Hemorrhagic transformation (HT) and cerebral edema (CED) are both major complications following ischemic stroke, but few studies have evaluated their overlap. We evaluated the frequency and predictors of CED/HT overlap and whether their co-occurrence impacts functional outcome more than each in isolation.

METHODS: 892 stroke patients enrolled in a prospective study had follow-up CT imaging evaluated for HT and CED; the latter was quantified using the ratio of hemispheric CSF volumes (with hemispheric CSF ratio < 0.90 used as the CED threshold). The interaction between HT and CED on functional outcome (using modified Rankin Scale at 3 months) was compared to that for each condition separately.

RESULTS: Among the 275 (31%) who developed HT, 233 (85%) manifested hemispheric CSF ratio < 0.9 (CED/HT), with this overlap group representing half of the 475 with measurable CED. Higher baseline NIHSS scores and larger infarct volumes were observed in the CED/HT group compared with those with CED or HT alone. Functional outcome was worse in those with CED/HT [median mRS 3 (IQR 2-5)] than those with CED [median 2 (IQR 1-4)] or HT alone [median 1 (IQR 0-2), p < 0.0001]. Overlap of CED/HT independently predicted worse outcome [OR 1.89 (95% CI: 1.12-3.18), p = 0.02] while HT did not; however, CED/HT was no longer associated with worse outcome after adjusting for severity of CED [adjusted OR 0.35 (95% CI: 0.23, 0.51) per 0.21 lower hemispheric CSF ratio, p < 0.001].

CONCLUSIONS: Most stroke patients with HT also have measurable CED. …

A Portable Photoacoustic Microscopy And Ultrasound System For Rectal Cancer Imaging, Sitai Kou, Sanskar Thakur, Ahmed Eltahir, Haolin Nie, Yitian Zhang, Andrew Song, Steven R Hunt, Matthew G Mutch, William C Chapman Jr, Quing Zhu

2020-Current year OA Pubs

Photoacoustic microscopy offers functional information regarding tissue vasculature while ultrasound characterizes tissue structure. Combining these two modalities provides novel clinical applications including response assessment among rectal cancer patients undergoing therapy. We have previously demonstrated the capabilities of a co-registered photoacoustic and ultrasound device

Evaluation Of Forces Applied To Tissues During Robotic-Assisted Surgical Tasks Using A Novel Force Feedback Technology, Michael M Awad, Mathew C Raynor, Mika Padmanabhan-Kabana, Lana Y Schumacher, Jeffrey A Blatnik

2020-Current year OA Pubs

BACKGROUND: The absence of force feedback (FFB) is considered a technical limitation in robotic-assisted surgery (RAS). This pre-clinical study aims to evaluate the forces applied to tissues using a novel integrated FFB technology, which allows surgeons to sense forces exerted at the instrument tips.

METHODS: Twenty-eight surgeons with varying experience levels employed FFB instruments to perform three robotic-assisted surgical tasks, including retraction, dissection, and suturing, on inanimate or ex-vivo models, while the instrument sensors recorded and conveyed the applied forces to the surgeon hand controllers of the robotic system. Generalized Estimating Equations (GEE) models were used to analyze the mean …

Evolution Of White Matter Hyperintensity Segmentation Methods And Implementation Over The Past Two Decades; An Incomplete Shift Towards Deep Learning, Maryam Rahmani, Donna Dierker, Lauren Yaeger, Patrick H Luckett, Andrei G Vlassenko, Christopher Owens, Hussain Jafri, Kyle Womack, Tammie L S Benzinger, Jin-Moo Lee, John C Morris, Manu S Goyal, Jeremy F Strain, Et Al.

2020-Current year OA Pubs

This systematic review examines the prevalence, underlying mechanisms, cohort characteristics, evaluation criteria, and cohort types in white matter hyperintensity (WMH) pipeline and implementation literature spanning the last two decades. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we categorized WMH segmentation tools based on their methodologies from January 1, 2000, to November 18, 2022. Inclusion criteria involved articles using openly available techniques with detailed descriptions, focusing on WMH as a primary outcome. Our analysis identified 1007 visual rating scales, 118 pipeline development articles, and 509 implementation articles. These studies predominantly explored aging, dementia, psychiatric disorders, and small …

Deletion Of Tissue Factor Pathway Inhibitor Isoform Beta Or Gamma, But Not Alpha, Improves Clotting In Hemophilic Mice, Irem Eldem, Lilian Antunes-Heck, Renumathi Subramanian, Nina M Lasky, Katrina Ashworth, Jorge Di Paola, Thomas J Girard

2020-Current year OA Pubs

BACKGROUND: Tissue factor pathway inhibitor (TFPI) regulates tissue factor-triggered coagulation. Humans and mice express transcripts encoding for multidistributed (endothelial, platelet, and plasma) 3-Kunitz domain TFPIα and endothelial membrane-anchored 2-Kunitz TFPIβ. Mice express a third transcript, γ, that encodes plasma lipoprotein-associated 2-Kunitz TFPI. In humans, proteolysis of α and/or β produces plasma lipoprotein-associated 2-Kunitz TFPI at lower levels. In clinical trials, monoclonal antibodies that target all TFPI isoforms extend coagulation and correct bleeding in hemophilic patients but with some thrombosis risks.

OBJECTIVES: To determine the impact of TFPI isoform-specific deletions on promoting clotting in hemophilic mice.

METHODS: Engineered TFPI isoform-specific, hemophilic …

Feasibility Of Interdisciplinary Evaluation In Non-Arthritic Hip Pain: A Randomized Trial, Sarah Depp, Lindsey Brown, Catherine Quatman-Yates, Randi Foraker, Emily S Patterson, W Kelton Vasileff, Stephanie Di Stasi

2020-Current year OA Pubs

BACKGROUND: Physical therapy and orthopaedic surgery are two common treatments for non-arthritic hip pain. Interdisciplinary evaluation across these disciplines may produce a more supportive treatment-planning process; however, the feasibility of such an evaluation remains unknown.

HYPOTHESIS OBJECTIVE: To assess the feasibility of an interdisciplinary evaluation with an orthopaedic surgeon and physical therapist for non-arthritic hip pain.

STUDY DESIGN: Observational feasibility study of a randomized controlled trial.

METHODS: Participants were randomized to an interdisciplinary (surgeon + physical therapist) or standard (surgeon) evaluation in a hip preservation clinic. Recruitment rate was recorded. Retention rate was calculated for all variables of interest. Enrollment …

Three- And Seven-Month Prostate-Specific Antigen Levels As Prognostic Markers For Overall Survival In Metastatic Hormone-Sensitive Prostate Cancer: Results From Swog S1216, A Phase 3 Randomized Trial Of Androgen Deprivation Plus Orteronel Or Bicalutamide, Mamta Parikh, Russell K Pachynski, Et Al.

2020-Current year OA Pubs

BACKGROUND: A robust decrease in prostate-specific antigen (PSA) in response to androgen deprivation therapy (ADT) has been evaluated as a prognostic factor in patients with metastatic hormone-sensitive prostate cancer (mHSPC) since 2006, but the treatment of mHSPC has since evolved to include intensified therapy.

OBJECTIVE: We assessed the association of PSA levels at 3 (PSA-3mo) and 7 (PSA-7mo) mo with overall survival (OS) in patients with mHSPC treated with ADT combined with either bicalutamide or orteronel in the S1216 phase 3 clinical trial.

DESIGN, SETTING, AND PARTICIPANTS: PSA responses to treatment of patients in the S1216 trial were categorized as: …

Practices Affecting Macitentan And Selexipag Patient Persistence Rates Utilizing Pulmonary Arterial Hypertension Clinical Site And Patient Perspectives (Persist): A Us Qualitative Analysis, Oksana A Shlobin, Gary Bruce, Gabriela Gomez-Rendon, Martha Kingman, Mohammad Rahman, Frances Rogers, Sean Studer, Tobore Tobore, Colleen Mcevoy

2020-Current year OA Pubs

This real-world study explored factors affecting persistence with macitentan and selexipag treatment from the perspective of 23 healthcare professionals (HCPs) and 134 patients with pulmonary arterial hypertension between 2019 and 2022. Continuous patient/HCP communication and education were key drivers of persistence, as were early discussion and management of side effects.

Continuous Adaptation Of Conversation Aids For Uterine Fibroids Treatment Options In A Four-Year Multi-Center Implementation Project, Danielle Schubbe, Tessa Madden, Et Al.

2020-Current year OA Pubs

BACKGROUND: Fibroids are non-cancerous uterine growths that can cause symptoms impacting quality of life. The breadth of treatment options allows for patient-centered preference. While conversation aids are known to facilitate shared decision making, the implementation of these aids for uterine fibroids treatments is limited. We aimed to develop two end-user-acceptable uterine fibroids conversation aids for an implementation project. Our second aim was to outline the adaptations that were made to the conversation aids as implementation occurred.

METHODS: We used a multi-phase user-centered participatory approach to develop a text-based and picture-enhanced conversation aid for uterine fibroids. We conducted a focus group …

Assessing The Response Results Of An Mhealth-Based Patient Experience Survey Among People Receiving Hiv Care In Lusaka, Zambia: Cohort Study, Jacob Mutale, Kombatende Sikombe, Boroma Mwale, Mwansa Lumpa, Sandra Simbeza, Chama Bukankala, Njekwa Mukamba, Aaloke Mody, Laura K Beres, Charles B Holmes, Carolyn Bolton Moore, Elvin H Geng, Izukanji Sikazwe, Jake M Pry

2020-Current year OA Pubs

BACKGROUND: This pilot study evaluates the effectiveness of mobile talk-time incentives in maintaining participation in a longitudinal mobile health (mHealth) data collection program among people living with HIV in Lusaka, Zambia. While mHealth tools, such as mobile phone surveys, provide vital health feedback, optimal incentive strategies to ensure long-term engagement remain limited. This study explores how different incentive levels affect response rates in multiple survey rounds, providing insights into effective methods for encouraging ongoing participation, especially in the context of Zambia's prepaid mobile system and multi-SIM usage, a common practice in sub-Saharan Africa.

OBJECTIVE: This study aimed to assess the …

Negative Effect Of Treatment With Mglur5 Negative Allosteric Modulator Afq056 On Blood Biomarkers In Young Individuals With Fragile X Syndrome, Dragana Protic, Stephanie Morris, Et Al.

2020-Current year OA Pubs

BACKGROUND: Fragile X syndrome, with an approximate incidence rate of 1 in 4000 males to 1 in 8000 females, is the most prevalent genetic cause of heritable intellectual disability and the most common monogenic cause of autism spectrum disorder. The full mutation of the Fragile X Messenger Ribonucleoprotein-1 gene, characterized by an expansion of CGG trinucleotide repeats (>200 CGG repeats), leads to fragile X syndrome. Currently, there are no targeted treatments available for fragile X syndrome. In a recent large multi-site trial, FXLEARN, the effects of the mGluR5 negative allosteric modulator, AFQ056 (mavoglurant), were investigated, but did not show …

How To Utilize Current Guidelines To Manage Patients With Cancer At High Risk For Heart Failure, Michelle Bloom, Jose A Alvarez-Cardona, Sarju Ganatra, Ana Barac, Iskra Pusic, Daniel Lenihan, Susan Dent

2020-Current year OA Pubs

Heart failure (HF) in patients with cancer is associated with high morbidity and mortality. The success of cancer therapy has resulted in an exponential rise in the population of cancer survivors, however cardiovascular disease (CVD) is now a major life limiting condition more than 5 years after cancer diagnosis [Sturgeon, Deng, Bluethmann, et al 40(48):3889-3897, 2019]. Prevention and early detection of CVD, including cardiomyopathy (CM) and HF is of paramount importance. The European Society of Cardiology (ESC) published guidelines on Cardio-Oncology (CO) [Lyon, López-Fernández, Couch, et al 43(41):4229-4361, 2022] detailing cardiovascular (CV) risk stratification, prevention, monitoring, diagnosis, and treatment throughout …

Inorganic Polyphosphate Promotes Colorectal Cancer Growth Via Trpm8 Receptor Signaling Pathway, Valentina Arrè, Chen Shen, Et Al.

2020-Current year OA Pubs

BACKGROUND: Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high-energy-supply molecules that assure tumor growth. A still less studied macromolecule is inorganic polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds of repeated orthophosphate units, iPolyP is essential for a wide variety of functions in mammalian cells, including the regulation of proliferative signaling pathways. Some evidence has suggested its involvement in carcinogenesis, although more studies need to be pursued. Moreover, iPolyP regulates several homeostatic processes in animals, spanning from energy metabolism to blood coagulation and tissue regeneration.

RESULTS: …

Safety Of Dostarlimab In Combination With Chemotherapy In Patients With Primary Advanced Or Recurrent Endometrial Cancer In A Phase Iii, Randomized, Placebo-Controlled Trial (Engot-En6-Nsgo/Gog-3031/Ruby), Annika Auranen, Matthew A Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.

OBJECTIVES: The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.

DESIGN: RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared …

A Multicenter, Randomized, Non-Comparative, Phase Ii Study Of Nivolumab ± Ipilimumab For Patients With Metastatic Sarcoma (Alliance A091401): Expansion Cohorts And Correlative Analyses, Nathan D Seligson, James L Chen, Austin C Goodrich, Brian A Van Tine, Jordan D Campbell, Allison L Richards, Cristina R Antonescu, David A Liebner, Mohammed M Milhem, Howard Streicher, William D Tap, Gary K Schwartz, Suzanne George, Sandra P D'Angelo

2020-Current year OA Pubs

BACKGROUND: In this open-label, randomized, non-comparative, multicenter phase II study (Alliance A091401) we report on three expansion cohorts treated with nivolumab (N) with and without ipilimumab (N+I) and provide a multi-omic correlative analysis of actionable biomarkers.

METHODS: Patients were randomized (non-comparative) to receive either N or N+I. The primary endpoint was a 6-month confirmed response rate (CRR) defined by Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included treatment-related adverse events (TRAEs), progression-free survival, and overall survival. Multi-omic correlative analyses were conducted using samples from both the primary and expansion cohorts.

RESULTS: A total of 66 patients were …

Awareness Of, Willingness To Use, And Experiences With Pre-Exposure Prophylaxis Among Youth In Nigeria, Titilola Gbaja-Biamila, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Youth (ages 14-24) in Nigeria have disproportionately high rates of new HIV infection. Pre-exposure prophylaxis could substantially reduce new infections among youth but has not been scaled up. This cross-sectional study aimed to assess Pre-exposure prophylaxis awareness, willingness to use, and prior use of Pre-exposure prophylaxis among youth in Nigeria.

METHODS: This is a secondary analysis of cross-sectional data from a quasi-experimental pilot study (clinical trial NCT04070287). The analysis focused on Pre-exposure prophylaxis awareness, willingness to use, and prior use among 324 youth recruited between September 2019 to March 2020. Descriptive statistics were calculated as frequencies and percentages for …

Length-Scale Study In Deep Learning Prediction For Non-Small Cell Lung Cancer Brain Metastasis, Haowen Zhou, Siyu Lin, Mark Watson, Cory T Bernadt, Oumeng Zhang, Ling Liao, Ramaswamy Govindan, Richard J Cote, Changhuei Yang

2020-Current year OA Pubs

Deep learning-assisted digital pathology has demonstrated the potential to profoundly impact clinical practice, even surpassing human pathologists in performance. However, as deep neural network (DNN) architectures grow in size and complexity, their explainability decreases, posing challenges in interpreting pathology features for broader clinical insights into physiological diseases. To better assess the interpretability of digital microscopic images and guide future microscopic system design, we developed a novel method to study the predictive feature length-scale that underpins a DNN's predictive power. We applied this method to analyze a DNN's capability in predicting brain metastasis from early-stage non-small-cell lung cancer biopsy slides. This …

A Basally Active Cgas-Sting Pathway Limits Sars-Cov-2 Replication In A Subset Of Ace2 Positive Airway Cell Models, Maritza Puray-Chavez, Jenna E Eschbach, Ming Xia, Kyle M Lapak, Qianzi Zhou, Ria Jasuja, Jiehong Pan, Jian Xu, Zixiang Zhou, Shawn Mohammed, Qibo Wang, Dana Q Lawson, Sanja Djokic, Gaopeng Hou, Siyuan Ding, Steven L Brody, Michael B Major, Dennis Goldfarb, Sebla B Kutluay

2020-Current year OA Pubs

Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks. SARS-CoV-2 replication in STING knockout cell lines and primary airway cultures induces ISG expression but only in uninfected bystander cells, demonstrating efficient antagonism …

Crinophagic Granules In Pancreatic Β Cells Contribute To Mouse Autoimmune Diabetes By Diversifying Pathogenic Epitope Repertoire, Hao Hu, Anthony N Vomund, Orion J Peterson, Neetu Srivastava, Tiandao Li, Lisa Kain, Wandy L Beatty, Bo Zhang, Chyi-Song Hsieh, Luc Teyton, Cheryl F Lichti, Emil R Unanue, Xiaoxiao Wan

2020-Current year OA Pubs

Autoimmune attack toward pancreatic β cells causes permanent loss of glucose homeostasis in type 1 diabetes (T1D). Insulin secretory granules store and secrete insulin but are also thought to be tissue messengers for T1D. Here, we show that the crinophagic granules (crinosome), a minor set of vesicles formed by fusing lysosomes with the conventional insulin dense-core granules (DCG), are pathogenic in T1D development in mouse models. Pharmacological inhibition of crinosome formation in β cells delays T1D progression without affecting the dominant DCGs. Mechanistically, crinophagy inhibition diminishes the epitope repertoire in pancreatic islets, including cryptic, modified and disease-relevant epitopes derived from …

Massively Parallel Characterization Of Insulator Activity Across The Genome, Clarice K Y Hong, Yawei Wu, Alyssa A Erickson, Jie Li, Arnold J Federico, Barak A Cohen

2020-Current year OA Pubs

A key question in regulatory genomics is whether cis-regulatory elements (CREs) are modular elements that can function anywhere in the genome, or whether they are adapted to certain genomic locations. To distinguish between these possibilities we develop MPIRE (Massively Parallel Integrated Regulatory Elements), a technology for recurrently assaying CREs at thousands of defined locations across the genome in parallel. MPIRE allows us to separate the intrinsic activity of CREs from the effects of their genomic environments. We apply MPIRE to assay three insulator sequences at thousands of genomic locations and find that each insulator functions in locations with distinguishable properties. …

Nur77 Protects The Bladder Urothelium From Intracellular Bacterial Infection, Christina A Collins, Chevaughn Waller, Ekaterina Batourina, Lokesh Kumar, Cathy L Mendelsohn, Nicole M Gilbert

2020-Current year OA Pubs

Intracellular infections by Gram-negative bacteria are a significant global health threat. The nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) was recently shown to sense cytosolic bacterial lipopolysaccharide (LPS). However, the potential role for Nur77 in controlling intracellular bacterial infection has not been examined. Here we show that Nur77 protects against intracellular infection in the bladder by uropathogenic Escherichia coli (UPEC), the leading cause of urinary tract infections (UTI). Nur77 deficiency in mice promotes the formation of UPEC intracellular bacterial communities (IBCs) in the cells lining the bladder lumen, leading to persistent infection in bladder tissue. Conversely, treatment with …

Treatment Outcomes Among Patients With A Positive Candida Culture Close To Randomization Receiving Rezafungin Or Caspofungin In The Restore Study, Alex Soriano, Marin Kollef, Et Al.

2020-Current year OA Pubs

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned subgroup analyses for patients with a positive culture close to randomization in ReSTORE.

METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before …

Durations Of Antibiotic Treatment For Acute Otitis Media And Variability In Prescribed Durations Across Two Large Academic Health Systems, Sophie E Katz, Timothy C Jenkins, Amy B Stein, Gale Thomas, Nancy Koenig, Gary Lucas Starnes, Jason G Newland, Ritu Banerjee, Holly M Frost

2020-Current year OA Pubs

BACKGROUND: Acute otitis media (AOM) accounts for roughly 25% of antibiotics prescribed to children annually. Despite national guidelines that recommend short (5-7 days) durations of antibiotics for children 2 years and older with AOM, most receive long (10 day) courses. This study aims to evaluate antibiotic durations prescribed for children aged 2-17 years with uncomplicated AOM across two pediatric academic health systems, and to assess the variability in prescribed durations between and within each system.

METHODS: Electronic medical record data from 135 care locations at two health systems were retrospectively analyzed. Outpatient encounters for children aged 2-17 years with a …

Evaluating Generative Ai's Ability To Identify Cancer Subtypes In Publicly Available Structured Genetic Datasets, Ethan Hillis, Kriti Bhattarai, Zachary Abrams

2020-Current year OA Pubs

BACKGROUND: Genetic data play a crucial role in diagnosing and treating various diseases, reflecting a growing imperative to integrate these data into clinical care. However, significant barriers such as the structure of electronic health records (EHRs), insurance costs for genetic testing, and the interpretability of genetic results impede this integration.

METHODS: This paper explores solutions to these challenges by combining recent technological advances with informatics and data science, focusing on the diagnostic potential of artificial intelligence (AI) in cancer research. AI has historically been applied in medical research with limited success, but recent developments have led to the emergence of …

Spatiotemporal Relationships Between Neuronal, Metabolic, And Hemodynamic Signals In The Awake And Anesthetized Mouse Brain, Xiaodan Wang, Jonah A Padawer-Curry, Annie R Bice, Byungchan Kim, Zachary P Rosenthal, Jin-Moo Lee, Manu S Goyal, Shannon L Macauley, Adam Q Bauer

2020-Current year OA Pubs

Neurovascular coupling (NVC) and neurometabolic coupling (NMC) provide the basis for functional magnetic resonance imaging and positron emission tomography to map brain neurophysiology. While increases in neuronal activity are often accompanied by increases in blood oxygen delivery and oxidative metabolism, these observations are not the rule. This decoupling is important when interpreting brain network organization (e.g., resting-state functional connectivity [RSFC]) because it is unclear whether changes in NMC/NVC affect RSFC measures. We leverage wide-field optical imaging in Thy1-jRGECO1a mice to map cortical calcium activity in pyramidal neurons, flavoprotein autofluorescence (representing oxidative metabolism), and hemodynamic activity during wake and ketamine/xylazine anesthesia. …

The Trim4 E3 Ubiquitin Ligase Degrades Tpl2 And Is Modulated By Oncogenic Kras, Sapana Bansod, Paarth B Dodhiawala, Yutong Geng, Ashenafi Bulle, Peng Liu, Lin Li, Reid Townsend, Patrick M Grierson, Jason M Held, Hema Adhikari, Kian-Huat Lim

2020-Current year OA Pubs

Loss-of-function mutations in the C terminus of TPL2 kinase promote oncogenesis by impeding its proteasomal degradation, leading to sustained protein expression. However, the degradation mechanism for TPL2 has remained elusive. Through proximity-dependent biotin identification (BioID), we uncovered tripartite motif-containing 4 (TRIM4) as the E3 ligase that binds and degrades TPL2 by polyubiquitination of lysines 415 and 439. The naturally occurring TPL2 mutants R442H and E188K exhibit impaired TRIM4 binding, enhancing their stability. We further discovered that TRIM4 itself is stabilized by another E3 ligase, TRIM21, which in turn is regulated by KRAS. Mutant KRAS recruits RNF185 to degrade TRIM21 and …

Conformational Ensembles In Klebsiella Pneumoniae Fimh Impact Uropathogenesis, Edward D B Lopatto, Jerome S Pinkner, Denise A Sanick, Robert F Potter, Lily X Liu, Jesús Bazán Villicaña, Kevin O Tamadonfar, Yijun Ye, Maxwell I Zimmerman, Nathaniel C Gualberto, Karen W Dodson, James W Janetka, David A Hunstad, Scott J Hultgren

2020-Current year OA Pubs

No abstract provided.