Digital Commons Network^™

Prognostic, Biological, And Structural Implications Of Flt3-Jmd Point Mutations In Acute Myeloid Leukemia: An Analysis Of Alliance Studies, Nadeen Anabtawi, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

The FLT3 gene frequently undergoes mutations in acute myeloid leukemia (AML), with internal tandem duplications (ITD) and tyrosine kinase domain (TKD) point mutations (PMs) being most common. Recently, PMs and deletions in the FLT3 juxtamembrane domain (JMD) have been identified, but their biological and clinical significance remains poorly understood. We analyzed 1660 patients with de novo AML and found FLT3-JMD mutations, mostly PMs, in 2% of the patients. Patients with FLT3-JMD mutations had a higher relapse rate and shorter disease-free survival than those with FLT3-TKD, whereas their relapse rate, disease-free and overall survival were not significantly different from those of …

Effect Of Midwife-Led Pelvic Floor Muscle Training On Prolapse Symptoms And Quality Of Life In Women With Pelvic Organ Prolapse In Ethiopia: A Cluster-Randomized Controlled Trial, Melese Siyoum, Rahel Nardos, Biniyam Sirak, Theresa Spitznagle, Wondwosen Teklesilasie, Ayalew Astatkie

2020-Current year OA Pubs

BACKGROUND: Pelvic organ prolapse (POP) is a common condition that can significantly impact a woman's quality of life. Pelvic floor muscle training (PFMT) is recommended as a first-line conservative treatment for prolapse, but evidence on its effectiveness from low-resource settings is limited. This study aimed to assess the effect of midwife-led PFMT on prolapse symptoms and health-related quality of life (HRQoL) among women with mild-to-moderate POP in Ethiopia.

METHODS AND FINDINGS: A community-based, parallel-groups, two-arm cluster-randomized controlled trial was conducted in Dale and Wonsho districts of Sidama Region, Ethiopia. Women with symptomatic POP stages I-III were randomized by cluster to …

Discrete Placental Gene Expression Signatures Accompany Diabetic Disease Classifications During Pregnancy, Enrico R Barrozo, Diana A Racusin, Michael D Jochum, Brandon T Garcia, Melissa A Suter, Melanie Delbeccaro, Cynthia Shope, Kathleen Antony, Kjersti M Aagaard

Faculty, Staff and Students Publications

Background: Gestational diabetes mellitus affects up to 10% of pregnancies and is classified into subtypes gestational diabetes subtype A1 (GDMA1) (managed by lifestyle modifications) and gestational diabetes subtype A2 (GDMA2) (requiring medication). However, whether these subtypes are distinct clinical entities or more reflective of an extended spectrum of normal pregnancy endocrine physiology remains unclear.

Objective: Integrated bulk RNA-sequencing (RNA-seq), single-cell RNA-sequencing (scRNA-seq), and spatial transcriptomics harbors the potential to reveal disease gene signatures in subsets of cells and tissue microenvironments. We aimed to combine these high-resolution technologies with rigorous classification of diabetes subtypes in pregnancy. We hypothesized that differences between …

Cerebrotendinous Xanthomatosis Occurs At High Frequency In Ashkenazi Jews, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Cerebrotendinous Xanthomatosis (CTX) is a treatable, inborn error of bile acids metabolism caused by pathogenic variants in CYP27A1. CTX is a multi-organ system disorder that progresses over decades. Clinical features include cerebellar dysfunction, pyramidal tract dysfunction, cognitive deficits and decline, peripheral neuropathy, chronic diarrhea, bilateral cataracts, and tendon xanthomas. Treatment is effective when started early, but diagnostic delays often result in individuals not being diagnosed until after the window of highest treatment efficacy. CTX is documented to occur in most global populations, however, no CTX-causing genetic variants have been reported in Ashkenazi Jews. We conducted a systematic review of every …

Assessing The Predicted Impact Of Single Amino Acid Substitutions In Calmodulin For Cagi6 Challenges, Paola Turina, Giuditta Dal Cortivo, Carlos A Enriquez Sandoval, Emil Alexov, David B Ascher, Giulia Babbi, Constantina Bakolitsa, Rita Casadio, Piero Fariselli, Lukas Folkman, Akash Kamandula, Panagiotis Katsonis, Dong Li, Olivier Lichtarge, Pier Luigi Martelli, Shailesh Kumar Panday, Douglas E V Pires, Stephanie Portelli, Fabrizio Pucci, Carlos H M Rodrigues, Marianne Rooman, Castrense Savojardo, Martin Schwersensky, Yang Shen, Alexey V Strokach, Yuanfei Sun, Junwoo Woo, Predrag Radivojac, Steven E Brenner, Daniele Dell'orco, Emidio Capriotti

Faculty, Staff and Students Publications

Recent thermodynamic and functional studies have been conducted to evaluate the impact of amino acid substitutions on Calmodulin (CaM). The Critical Assessment of Genome Interpretation (CAGI) data provider at University of Verona (Italy) measured the melting temperature (Tm) and the percentage of unfolding (%unfold) of a set of CaM variants (CaM challenge dataset). Thermodynamic measurements for the equilibrium unfolding of CaM were obtained by monitoring far-UV Circular Dichroism as a function of temperature. These measurements were used to determine the Tm and the percentage of protein remaining unfolded at the highest temperature.

The CaM challenge dataset, comprising a total of …

Trends And Disparities In Antiretroviral Therapy Prescription Rates Among Us Medicare Beneficiaries With Hiv, Xiaoying Yu, Yong-Fang Kuo, Ashley A Dike, Tsola Efejuku, Mukaila A Raji, Abbey B Berenson, Thomas P Giordano

Faculty, Staff and Students Publications

Objective: Our objective was to evaluate antiretroviral therapy (ART) prescription rates over time among US Medicare enrolees with HIV and to describe disparities in ART prescription and associated factors.

Method: We constructed successive cross-sectional cohorts including adult enrollees with HIV and fee-for-service coverage and Part D enrolment in US Medicare between 2007 and 2019. We calculated the percentage of receipt of any ART prescription (ART%) in a calendar year by sex, age, and original Medicare entitlement and calculated age-sex standardized ART% over time. We used multivariable logistic regression to assess the association between ART prescription and sociodemographic factors and chronic …

Infantile Myofibromatosis: Small Bumps Pose Big Problems, Hillary C Lee, Amee A Amin, Kudakwashe R Chikwava, Valeria R Smith, Caraciolo J Fernandes

Faculty, Staff and Students Publications

Background

Infantile myofibromatosis (IM) is a disorder characterized by proliferation of benign myofibroblastic tumors that typically manifest as solitary or multiple nodules in the skin, muscle, bone, subcutaneous tissues, and visceral organs and can pose significant morbidity and mortality risks, particularly in cases involving visceral organs or causing functional impairment. These soft tissue lesions are the most prevalent benign fibrous tumors that present before age two and can undergo spontaneous regression or are amenable to surgical resection.

Case

A preterm, male infant was born via Caesarean section to a mother with a trichorionic, triamniotic pregnancy following preterm labor. Within the …

Reply: A Positive Step Toward Cost-Effective And Accessible Hcc Detection Awaits Further Validation, Hashem B El-Serag, Qingchun Jin, Tayob Nabihah

Faculty, Staff and Students Publications

No abstract provided.

Inappropriate Laboratory Testing: Significant Waste Quantified By A Large-Scale Year-Long Study Of Medicare And Commercial Payer Reimbursement, Dave Smart, Jeff Schreier, Ila R Singh

Faculty, Staff and Students Publications

Context.—: Laboratory testing, beyond what is essential for managing health, is considered low-value care, posing patient risks and wasting resources. Measuring excess testing on a national level is crucial to identify waste and optimize healthcare resource allocation for maximum impact.

Objective.—: To measure inappropriate laboratory testing and its cost across Medicare and many US commercial payers.

Design.—: A retrospective analysis on 2019 claims data measured the frequency of 4 commonly used laboratory tests among 64 million individuals with Medicare and 168 million with commercial insurance. Tests included 25-hydroxy vitamin D, prostate-specific antigen, lipid panel, and hemoglobin A1c. Clinical guidelines, medical …

Exploring The Differences Between Brca Mutated And Hrwild-Type High Grade Serous Ovarian Cancer: A Multiomic Analysis, Ayesha B Alvero, Sharon Wu, Alex Farrell, Seongho Kim, John J Wallbillich, Ira Winer, Robert Morris, David Spetzler, Matthew L Anderson, Alberto Puccini, Nathaniel L Jones, Thomas J Herzog, Premal H Thaker, Gil Mor, Radhika P Gogoi

2020-Current year OA Pubs

OBJECTIVE: The purpose of this study was to evaluate the transcriptomic profile of BRCA1 mutant (BRCA1mut) and BRCA2 mutant (BRCA2mut) HGSOC compared to homologous recombination wild-type (HRwt) tumors utilizing the CARIS database.

METHODS: Next-generation and Whole Transcriptome Sequencing (WTS; Caris Life Sciences, Phoenix, AZ) was performed on a total of 2745 HGSOC tumor samples. BRCA mutations were defined as variants resulting in loss-of-function of the protein and HRwt was defined as samples wildtype for aberrations in both BRCA1 and BRCA2, as well as for 28 other HR genes. HRwt group was further classified into HRwt/LOH-low (< 16 %) and HRwt/LOH-high (≥16 %). Genomic analysis consists of mutation analysis and measurements of TMB and MSI. Transcriptomic analysis included identification of Differentially expressed genes (DEGs), GSEA and immune deconvolution.

RESULTS: We identified 519 …

Integrative Analysis Of The 3d Genome And Epigenome In Mouse Embryonic Tissues, Miao Yu, Yang E Li, Et Al.

2020-Current year OA Pubs

While a rich set of putative cis-regulatory sequences involved in mouse fetal development have been annotated recently on the basis of chromatin accessibility and histone modification patterns, delineating their role in developmentally regulated gene expression continues to be challenging. To fill this gap, here we mapped chromatin contacts between gene promoters and distal sequences across the genome in seven mouse fetal tissues and across six developmental stages of the forebrain. We identified 248,620 long-range chromatin interactions centered at 14,138 protein-coding genes and characterized their tissue-to-tissue variations and developmental dynamics. Integrative analysis of the interactome with previous epigenome and transcriptome datasets …

Spatial Proteomics Of Onchocerca Volvulus With Pleomorphic Neoplasms Shows Local And Systemic Dysregulation Of Protein Expression, Lucia S. Di Maggio, Kerstin Fischer, Bruce A. Rosa, Devyn Yates, Byoung-Kyu Cho, Jessica Lukowski, Antonia Zamacona Calderon, Minsoo Son, Young Ah Goo, Nicholas O. Opoku, Gary J. Weil, Makedonka Mitreva, Peter U. Fischer

2020-Current year OA Pubs

Onchocerca volvulus is the agent of onchocerciasis (river blindness) and targeted by WHO for elimination though mass drug administration with ivermectin. A small percentage of adult female worms develop pleomorphic neoplasms (PN) which occur more frequently after ivermectin treatment. Worms with PN have a lower life expectancy and improved understanding of proteins expressed in PN and their impact on different tissues could help elucidate the mechanisms of macrofilaricidal activity of ivermectin. Within paraffin embedded nodules removed after ivermectin treatment, we detected 24 (5.6%) O. volvulus females with PN. To assess the protein inventory of the PN and identify proteins potentially …

Local Genetic Covariance Analysis With Lipid Traits Identifies Novel Loci For Early-Onset Alzheimer's Disease, Nicholas R. Ray, Joseph Bradley, Elanur Yilmaz, Caghan Kizil, Jiji T. Kurup, Eden R. Martin, Hans-Ulrich Klein, Brian W Kunkle, David A. Bennett, Philip L. De Jager, Alzheimer’S Disease Genetics Consortium, Gary W. Beecham, Carlos Cruchaga, Christiane Reitz

2020-Current year OA Pubs

The genetic component of early-onset Alzheimer disease (EOAD), accounting for ~10% of all Alzheimer's disease (AD) cases, is largely unexplained. Recent studies suggest that EOAD may be enriched for variants acting in the lipid pathway. The current study examines the shared genetic heritability between EOAD and the lipid pathway using genome-wide multi-trait genetic covariance analyses. Summary statistics were obtained from the GWAS meta-analyses of EOAD by the Alzheimer's Disease Genetics Consortium (n=19,668) and five blood lipid traits by the Global Lipids Genetics Consortium (n=1,320,016). The significant results were compared between the EOAD and lipids GWAS and genetic covariance analyses were …

Effect Of Telemedicine Support For Intraoperative Anaesthesia Care On Postoperative Outcomes: The Tectonics Randomised Clinical Trial, Christopher R King, Bradley A Fritz, Stephen H Gregory, Thaddeus P Budelier, Arbi Ben Abdallah, Alex Kronzer, Daniel L Helsten, Brian Torres, Sherry L Mckinnon, Sandhya Tripathi, Mohamed Abdelhack, Shreya Goswami, Arianna Montes De Oca, Divya Mehta, Miguel A Valdez, Evangelos Karanikolas, Omokhaye Higo, Paul Kerby, Bernadette Henrichs, Troy S Wildes, Mary C Politi, Joanna Abraham, Michael S Avidan, Thomas Kannampallil

2020-Current year OA Pubs

BACKGROUND: Telemedicine may help improve care quality and patient outcomes. Telemedicine for intraoperative decision support has not been rigorously studied.

METHODS: This was a single-centre randomised clinical trial of unselected adult surgical patients. Patients were randomised to receive usual care or decision support from a telemedicine service, which provided real-time recommendations to intraoperative anaesthesia clinicians based on case reviews and physiological alerts. ORs were randomised 1:1. The co-primary outcomes were 30-day all-cause mortality, respiratory failure, acute kidney injury, and delirium in the intensive care unit, analysed by intention to treat.

RESULTS: Between July 1, 2019, and January 31, 2023, a …

Combining Radioembolization And Immune Checkpoint Inhibitors For The Treatment Of Hepatocellular Carcinoma: The Quest For Synergy, Christopher D Malone, Suryansh Bajaj, Aiwu He, Kabir Mody, Ryan M Hickey, Ammar Sarwar, Sunil Krishnan, Tushar C Patel, Beau B Toskich

2020-Current year OA Pubs

Hepatocellular carcinoma is a leading and increasing contributor to cancer-related death worldwide. Recent advancements in both liver-directed therapies in the form of yttrium-90 (

Relationships Between Brain Glucose Metabolism Patterns And Impaired Glycemic Status: A Systematic Review Of Fdg-Pet Studies With A Focus On Alzheimer's Disease, Setareh Soltani, Mahsa Dolatshahi, Sara Soltani, Kian Khazaei, Maryam Rahmani, Cyrus A Raji

2020-Current year OA Pubs

It is well-established that individuals with type 2 diabetes have an increased risk of developing cognitive impairment and Alzheimer's disease (AD). However, it is not fully determined how insulin resistance and type 2 diabetes are related to AD-related brain glucose metabolism abnormalities. For this aim, we performed a systematic review of the studies investigating the association between cerebral glucose metabolism and glycemic status, including diabetes, insulin resistance, or hyperglycemia. Medline, Embase, and Cochrane databases were searched (till February 2, 2025). All English full-text papers studying 18F-FDG-PET that investigated the association between cerebral FDG uptake or cerebral metabolism rate and glycemic …

Detection Of Alternative Lengthening Of Telomeres Via Chromogenic In Situ Hybridization For The Prognostication Of Pannets And Other Neoplasms, Christopher M Heaphy, Ta-Chiang Liu, Dengfeng Cao, Et Al.

2020-Current year OA Pubs

Molecular studies have shown alternative lengthening to telomeres (ALT) to be an important prognostic biomarker of shorter relapse-free survival (RFS) for patients with pancreatic neuroendocrine tumors (PanNETs) and other neoplasms. However, the preferred method of detecting ALT in tissue is by fluorescence in situ hybridization (FISH), which has several clinical limitations. These issues necessitate the creation of a chromogenic ALT assay that can be easily implemented into routine practice. A chromogenic in situ hybridization (CISH) assay was developed using genetically modified osteosarcoma cell lines, 20 normal pancreata, 20 ALT-positive PanNETs, and 20 ALT-negative PanNETs. Thereafter, it was validated on a …

Prehospital Cricothyrotomy: A Narrative Review Of Technical, Educational, And Operational Considerations For Procedure Optimization, Aaron J Lacy, Michael J Kim, James L Li, Alexander Croft, Erin E Kane, Jason C Wagner, Philip W Walker, Christine M Brent, Jeremy J Brywczynski, Amanda C Mathews, Brit Long, Alex Koyfman, Bridgette Svancarek

2020-Current year OA Pubs

BACKGROUND: Definitive airway management is a requisite skill in the prehospital setting, most often accomplished with either an endotracheal tube or supraglottic airway. When clinicians encounter a cannot oxygenate and cannot ventilate scenario, a patient's airway still must be secured. Prehospital cricothyrotomy is a high acuity, low frequency procedure used to secure the airway through the anterior neck. Patients who require cricothyrotomy often have significant comorbid conditions and mortality, and there can be a high rate of procedural complications. The ability to perform a cricothyrotomy is within the scope of practice for many prehospital clinicians and mastery of the procedure …

Cagi6 Id Panel Challenge: Assessment Of Phenotype And Variant Predictions In 415 Children With Neurodevelopmental Disorders (Ndds), Maria Cristina Aspromonte, Alessio Del Conte, Shaowen Zhu, Wuwei Tan, Yang Shen, Yexian Zhang, Qi Li, Maggie Haitian Wang, Giulia Babbi, Samuele Bovo, Pier Luigi Martelli, Rita Casadio, Azza Althagafi, Sumyyah Toonsi, Maxat Kulmanov, Robert Hoehndorf, Panagiotis Katsonis, Amanda Williams, Olivier Lichtarge, Su Xian, Wesley Surento, Vikas Pejaver, Sean D Mooney, Uma Sunderam, Rajgopal Srinivasan, Alessandra Murgia, Damiano Piovesan, Silvio C E Tosatto, Emanuela Leonardi

Faculty, Staff and Students Publications

The Genetics of Neurodevelopmental Disorders Lab in Padua provided a new intellectual disability (ID) Panel challenge for computational methods to predict patient phenotypes and their causal variants in the context of the Critical Assessment of the Genome Interpretation, 6th edition (CAGI6). Eight research teams submitted a total of 30 models to predict phenotypes based on the sequences of 74 genes (VCF format) in 415 pediatric patients affected by Neurodevelopmental Disorders (NDDs). NDDs are clinically and genetically heterogeneous conditions, with onset in infant age. Here, we assess the ability and accuracy of computational methods to predict comorbid phenotypes based on clinical …

Trends In Kidney Allograft Failure Among First-Time Transplant Recipients In The United States, Pascale Khairallah, Elizabeth C Lorenz, Amy Waterman, Nidhi Aggarwal, Akshta Pai, Wolfgang C Winkelmayer, Jingbo Niu

Faculty, Staff and Students Publications

Rationale & objective: The management and outcomes of kidney transplant recipients have evolved over the past 3 decades. This study of US patients whose first kidney allograft failed examined long-term trends in subsequent waitlisting, retransplantation, and all-cause mortality.

Study design: Retrospective cohort study.

Setting & participants: Patients recorded in the US Renal Data System (USRDS) whose first kidney allograft failed between 1990 and 2019.

Exposure: The 5-year period in which the allograft failure occurred: 1990-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014, or 2015-2019.

Outcome: (1) Waitlisting for retransplantation, (2) retransplantation, and (3) all-cause mortality following first allograft failure.

Analytical approach: Competing risk …

Use Of Robust Norming To Create A Sensitive Cognitive Summary Score In De Novo Parkinson's Disease: An Illustrative Example, Daniel Weintraub, Michael C Brumm, Ryan Kurth, Michele K York

Faculty, Staff and Students Publications

Background: Cognitive impairment is common at all stages of Parkinson's disease (PD), but there is no consensus on which neuropsychological tests to use or how to interpret cognitive battery results. A cognitive summary score (CSS) combines the richness of a neuropsychological battery with the simplicity of a single score.

Objective: The objective of this study was to determine whether a CSS created using robust norming can detect early cognitive deficits in de novo, untreated PD.

Methods: Baseline cognitive data from PD participants and healthy control participants (HCs) in the Parkinson's Progression Markers Initiative were used to (1) create a robust …

High-Dose Methotrexate Usage Without Drug-Level Monitoring In Advanced Pediatric Mature B-Cell Non-Hodgkin Lymphoma In A Resource-Limited Setting In Malawi, Rizine R Mzikamanda, Loviisa Mulanje, Casey L Mcatee, Apatsa Matatiyo, Zoe Mwale, Grace Chirwa, Watipaso Wanda, Atupele Miranda Mpasa, Stella Wachepa, Minke H W Huibers, Steve Martin, Tamiwe Tomoka, Maurice Mulenga, Yuri Fedoriw, Gugulethu Mapurisa, Julie M Gastier Foster, Nader El-Mallawany, Katherine D Westmoreland, Peter Wasswa, Carl E Allen, Nmazuo Ozuah

Faculty, Staff and Students Publications

Purpose: Excellent survival for advanced (stages II with high lactate dehydrogenase, III, and IV) pediatric mature B-cell non-Hodgkin lymphoma (MB-NHL) has been achieved with intensive regimens, but adoption in sub-Saharan Africa is limited by inadequate supportive care. We provide real-world data on treating advanced MB-NHL with high-dose methotrexate (HD-MTX; ≥1,000 mg/m2/cycle) where real-time serum MTX monitoring is unavailable.

Methods: We identified two cohorts-a retrospective (January 2017-December 2020) cohort treated with 1,000 or 3,000 mg/m2/cycle of HD-MTX and a prospective (July 2022-July 2023) cohort-with a modified LMB96 protocol containing 3,000 mg/m2/cycle of HD-MTX. All doses of HD-MTX were given over 3 …

Pilot Screening For Prodromal Parkinson’S Disease In Post-9/11 Veterans With Probable Rapid Eye Movement Sleep Behavior Disorder, Melissa B Jones, Dakota Broadway, Taryn White, George R Jackson, Supriya Singh, Ruosha Li, Erik K St Louis, Laura E Marsh, Ricardo E Jorge

Faculty, Staff and Students Publications

This pilot examined prodromal markers in post-9/11 Veterans with TBI and probable REM sleep behavior disorder (N = 12). RBD was confirmed in 5 of 10 (50 %) participants with polysomnography. Veterans with subthreshold parkinsonism had lower olfactory scores. Future studies should quantify REM sleep without atonia and include broader markers.

Multiethnic Growth Standards For Fetal Body Composition And Organ Volumes Derived From 3d Ultrasonography, Katherine L Grantz, Wesley Lee, Lauren M Mack, Magdalena Sanz Cortes, Luis F Goncalves, Jimmy Espinoza, Roger B Newman, William A Grobman, Ronald J Wapner, Karin Fuchs, Mary E D'Alton, Daniel W Skupski, John Owen, Anthony Sciscione, Deborah A Wing, Michael P Nageotte, Angela C Ranzini, Edward K Chien, Sabrina Craigo, Seth Sherman, Robert E Gore-Langton, Dian He, Fasil Tekola-Ayele, Cuilin Zhang, Jagteshwar Grewal, Zhen Chen

Faculty, Staff and Student Publications

Background: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort.

Objective: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by 3-dimensional ultrasonography and compare growth trajectories with …

Long Covid Illness: Disparities In Understanding And Receipt Of Care In Emergency Department Populations, Robert M Rodriguez, Karen Reyes, Vijaya Arun Kumar, Brian Chinnock, Stephanie A Eucker, Kristin L Rising, Zubaid Rafique, Michael Gottlieb, Graham Nichol, Dana Morse, Melanie Molina, Mireya I Arreguin, Lindsey Shughart, Christopher Conn, Svea Eckstrand, Heba Mesbah, Lauren Chakraborty, Robert D Welch

Faculty, Staff and Students Publications

Study objective: Most long coronavirus disease (long COVID) studies rely on traditional surveillance methods that miss underserved populations who use emergency departments (EDs) as their primary health care source. In medically underserved ED populations, we sought to determine (1) whether there are gaps in awareness and self-declared understanding about long COVID illness, and (2) the prevalence, impact on school/work attendance, and receipt of care for long COVID symptoms.

Methods: This study was a cross-sectional, convenience sample survey study of adult patients at 11 geographically representative US EDs from December 2022 to October 2023. Awareness and self-declared understanding about long COVID …

Patient Consent And The Right To Notice And Explanation Of Ai Systems Used In Health Care, Meghan E Hurley, Benjamin H Lang, Kristin Marie Kostick-Quenet, Jared N Smith, Jennifer Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

Given the need for enforceable guardrails for artificial intelligence (AI) that protect the public and allow for innovation, the U.S. Government recently issued a Blueprint for an AI Bill of Rights which outlines five principles of safe AI design, use, and implementation. One in particular, the right to notice and explanation, requires accurately informing the public about the use of AI that impacts them in ways that are easy to understand. Yet, in the healthcare setting, it is unclear what goal the right to notice and explanation serves, and the moral importance of patient-level disclosure. We propose three normative functions …

Assessing The Predicted Impact Of Single Amino Acid Substitutions In Mapk Proteins For Cagi6 Challenges, Paola Turina, Maria Petrosino, Carlos A Enriquez Sandoval, Leonore Novak, Alessandra Pasquo, Emil Alexov, Muttaqi Ahmad Alladin, David B Ascher, Giulia Babbi, Constantina Bakolitsa, Rita Casadio, Jianlin Cheng, Piero Fariselli, Lukas Folkman, Akash Kamandula, Panagiotis Katsonis, Minghui Li, Dong Li, Olivier Lichtarge, Sajid Mahmud, Pier Luigi Martelli, Debnath Pal, Shailesh Kumar Panday, Douglas E V Pires, Stephanie Portelli, Fabrizio Pucci, Carlos H M Rodrigues, Marianne Rooman, Castrense Savojardo, Martin Schwersensky, Yang Shen, Alexey V Strokach, Yuanfei Sun, Junwoo Woo, Predrag Radivojac, Steven E Brenner, Roberta Chiaraluce, Valerio Consalvi, Emidio Capriotti

Faculty, Staff and Students Publications

New thermodynamic and functional studies have been recently conducted to evaluate the impact of amino acid substitutions on the Mitogen Activated Protein Kinases 1 and 3 (MAPK1/3). The Critical Assessment of Genome Interpretation (CAGI) data provider, at Sapienza University of Rome, measured the unfolding free energy and the enzymatic activity of a set of variants (MAPK challenge dataset). Thermodynamic measurements for the denaturant-induced equilibrium unfolding of the phosphorylated and unphosphorylated forms of the MAPKs were obtained by monitoring the far-UV circular dichroism and intrinsic fluorescence changes as a function of denaturant concentration. These values have been used to calculate the …

A Multicenter Training And Interrater Reliability Study Of The Based Score For Infantile Epileptic Spasms Syndrome, John R Mytinger, Dara V F Albert, Shawn C Aylward, Christopher W Beatty, Sonam Bhalla, Sonal Bhatia, Guy N Brock, Micheal A Ciliberto, Purva R Choudhari, Daniel J Clark, Jennifer Madan Cohen, Theresa M Czech, Megan M Fredwall, Ernesto Gonzalez-Giraldo, Chellamani Harini, Senyene E Hunter, Amanda G Sandoval Karamian, Akshat Katyayan, Isaac Kistler, Neil Kulkarni, Virginia B Liu, Corinne Mccabe, Thomas Murray, Kerri Neville, Shital H Patel, Spriha Pavuluri, Donald J Phillips, Debopam Samanta, Deepa Sirsi, Emily M Spelbrink, Carl E Stafstrom, Maija Steenari, Danielle S Takacs, Tyler Terrill, Linh Tran, Jorge Vidaurre, Daniel W Shrey

Faculty, Staff and Students Publications

PURPOSE: The best possible outcomes in infantile epileptic spasms syndrome require electroclinical remission; however, determining electrographic remission is not straightforward. Although the determination of hypsarrhythmia has inadequate interrater reliability (IRR), the Burden of AmplitudeS and Epileptiform Discharges (BASED) score has shown promise for the reliable interictal assessment of infantile epileptic spasms syndrome. Our aim was to develop a BASED training program and assess the IRR among learners. We hypothesized moderate or better IRR for the final BASED score and the presence or absence of epileptic encephalopathy (+/-EE).

METHODS: Using a web-based application, 31 learners assessed 12 unmarked EEGs (length 1-6 …

Comprehensive Normalization And Binary Classification Methods For Enhanced Sensitivity And Reproducibility In Luminex Assay Quantitation, B A Burns, C A Shaw, M Chandra, C S Forconi, A M Moormann, V Konduri, V N Tubman, W K Decker

Faculty, Staff and Students Publications

The Luminex assay is a powerful tool for large-scale quantitation of antibody levels and cytokines, but its utility can be limited by issues of specificity, sensitivity, and reproducibility. The corrections for background fluorescence and machine drift are essential steps in the normalization process. However, traditional methods often oversimplify these steps, failing to account for the complexity of the data, leading to the introduction of error and decreasing the sensitivity and reproducibility of the analysis. Furthermore, conventional methods to determine cut-points in binary measures do not consider the true distribution of the data, leading to arbitrary cut-points that compromise the integrity …

Impact Of Mass Drug Administration With Ivermectin, Diethylcarbamazine, And Albendazole For Lymphatic Filariasis On Hookworm And Strongyloides Stercoralis Infections In Papua New Guinea, Jannet A. Tobon Ramos, Tobias Maure, Lenore Carias, Daphne Lew, Charles Goss, Anna Samuel, Livingstone Tavul, Peter U. Fischer, Gary J. Weil, Moses Laman, Leanne J. Robinson, William Pomat, Christopher L. King

2020-Current year OA Pubs

BACKGROUND: Persons with lymphatic filariasis (LF) are often co-infected with soil-transmitted helminths. A single co-administered dose of ivermectin/diethylcarbamazine/albendazole (IDA) is recommended by WHO for mass drug administration (MDA) for LF instead of diethylcarbamazine/albendazole (DA) in Papua New Guinea (PNG). We compared the effectiveness of a single round of MDA with IDA or DA on hookworm and strongyloidiasis in PNG.

METHODOLOGY/PRINCIPAL FINDINGS: This study was conducted as part of a cluster randomized trial of MDA with IDA versus DA for LF in individuals willing to provide stool and blood samples at baseline and 12 months after MDA. Participants from 23 villages …