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Full-Text Articles in Entire DC Network
Donor-Specific Transplant Outcomes From Bmt Ctn 1702: A Multicenter Prospective Biologic Assignment Trial, Asad Bashey, Iskra Pusic, Et Al.
Donor-Specific Transplant Outcomes From Bmt Ctn 1702: A Multicenter Prospective Biologic Assignment Trial, Asad Bashey, Iskra Pusic, Et Al.
2020-Current year OA Pubs
Newer approaches to control alloreactivity may produce similar transplant outcomes using HLA-mismatched donors vs HLA-matched unrelated donors (MUD). However, prospective comparisons are lacking. BMT CTN 1702 used a donor search prognosis score to assign patients to an 8/8 HLA MUD or the center's preference of haploidentical related donors (HAPLO), mismatched unrelated donors (MMUD), or umbilical cord blood (UCB). Outcomes of MUD were compared to HAPLO, MMUD, and UCB transplantation after adjusting for covariates. Patients (n = 1179 [93% adults]) underwent transplantation with MUD (n = 772), HAPLO (n = 254), MMUD (n = 112), and UCB (n = 41) at …
Compbio And Miras-A Multi-Omic Analysis Platform Built On A Memory-Based Intelligence Engine, Ruteja A Barve, Chad E Storer, Wayne D Hoxsie, Curtis Marcum, Joshua F Mcmichael, Jared M Lalmansingh, Brittany K Smith, Mark R Johnson, Daniel J Kuster, Richard D Head
Compbio And Miras-A Multi-Omic Analysis Platform Built On A Memory-Based Intelligence Engine, Ruteja A Barve, Chad E Storer, Wayne D Hoxsie, Curtis Marcum, Joshua F Mcmichael, Jared M Lalmansingh, Brittany K Smith, Mark R Johnson, Daniel J Kuster, Richard D Head
2020-Current year OA Pubs
As molecular and cellular technologies have advanced, the need to analyze and interpret the resulting vast and multi-modal data into actionable intelligence has become a rate-limiting factor in scientific advancement. While traditional knowledgebase-pathway tools and LLM-based AI tools provide a degree of support in data interpretation, both exhibit known limitations. Presented here is the CompBio multi-omic analysis platform built upon Memory-based Intelligent Reasoning System (MIRaS), an associative reasoning engine grounded in episodic and semantic memory, capable of inferring biological relationships directly from stored knowledge rather than from model training. The MIRaS system is not dependent on human-curated pathway knowledgebases, provides …
Premarket Clinical Evidence Strength And Recalls Of High-Risk Therapeutic Medical Devices, Maryam Mooghali, Faaizah Arshad, Vinay K Rathi, Kushal T Kadakia, Alexander O Everhart, Joseph S Ross, Sanket S Dhruva
Premarket Clinical Evidence Strength And Recalls Of High-Risk Therapeutic Medical Devices, Maryam Mooghali, Faaizah Arshad, Vinay K Rathi, Kushal T Kadakia, Alexander O Everhart, Joseph S Ross, Sanket S Dhruva
2020-Current year OA Pubs
IMPORTANCE: High-risk medical devices approved through the US Food and Drug Administration (FDA) premarket approval (PMA) pathway may be supported by limited premarket clinical evidence, leaving uncertainties about safety. Whether device, premarket clinical evidence, or regulatory characteristics are associated with subsequent device recalls is unknown.
OBJECTIVE: To examine the association between device, premarket clinical evidence, and regulatory characteristics and serious recalls among high-risk therapeutic devices.
DESIGN AND SETTING: This cross-sectional study reviewed 193 high-risk therapeutic medical devices approved through the FDA's PMA pathway between January 1, 2014, and December 31, 2023. Data were analyzed between August 2025 and December 2025. …
Sex-Aware Causal Inference Assessment Of The Immune System In Complex Neurodegenerative Diseases, Frida Lona-Durazo, Ross P Byrne, Marc-Olivier Pilon, Michael D Greicius, Marie-Pierre Dubé, Michael E Belloy, Russell L Mclaughlin, Sarah A Gagliano Taliun
Sex-Aware Causal Inference Assessment Of The Immune System In Complex Neurodegenerative Diseases, Frida Lona-Durazo, Ross P Byrne, Marc-Olivier Pilon, Michael D Greicius, Marie-Pierre Dubé, Michael E Belloy, Russell L Mclaughlin, Sarah A Gagliano Taliun
2020-Current year OA Pubs
Sex differences, in terms of prevalence, symptoms and disease progression, are established in the aetiology of complex neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease, but the underlying biology driving these differences remains poorly understood. There is emerging evidence from genetic and functional analyses affirming the role of the immune system in such diseases, but a thorough assessment of sex differences in the link between the immune system and neurodegenerative diseases remains lacking. Here, we applied a robust causal inference approach, two-sample Mendelian randomization, to evaluate the causal effect of immune-related protein levels on three neurodegenerative diseases …
Nextlongiso: A Comprehensive Nextflow Pipeline For Multi-Dimensional Long-Read Rna-Seq Analysis, Jiang Tan, Yuqing Wu, Yidan Sun
Nextlongiso: A Comprehensive Nextflow Pipeline For Multi-Dimensional Long-Read Rna-Seq Analysis, Jiang Tan, Yuqing Wu, Yidan Sun
2020-Current year OA Pubs
SUMMARY: Long-read RNA sequencing technologies, including Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT), enable direct characterization of full-length transcripts and transcriptome complexity. However, analysis of long-read RNA-seq data remains fragmented across multiple tools, limiting the ability to obtain a unified view of transcript structure, expression, and regulatory variation in long-read transcriptomes. We present NextLongIso, a scalable and reproducible Nextflow pipeline that enables coordinated analysis of multiple layers of transcript regulation. Rather than focusing solely on transcript reconstruction, NextLongIso integrates transcript discovery with downstream regulatory analyses to jointly characterize alternative splicing, isoform switching, transcript boundary dynamics (including alternative promoters and …
Effects Of Concurrent Neuropathologies With Alzheimer Disease Neuropathologic Change On Cognitive Decline: Minimal Impact Of Vascular Brain Injury Compared With Other Combinations, Sarah M Yasuda, Charles Mock, Kathryn Gauthreaux, Kwun C G Chan, C Dirk Keene, Jessica E Culhane, Yen-Chi Chen, Walter Kukull
Effects Of Concurrent Neuropathologies With Alzheimer Disease Neuropathologic Change On Cognitive Decline: Minimal Impact Of Vascular Brain Injury Compared With Other Combinations, Sarah M Yasuda, Charles Mock, Kathryn Gauthreaux, Kwun C G Chan, C Dirk Keene, Jessica E Culhane, Yen-Chi Chen, Walter Kukull
2020-Current year OA Pubs
We examined cognitive changes associated with several neuropathologic entities, alone and in combination. We studied 808 participants from the National Alzheimer's Coordinating Center to assess associations between neuropathologic diagnoses (from autopsy) and neuropsychologic test scores (trajectories over time for 5 domains: overall cognition, episodic memory, attention, language, executive function). Neuropathologies included: Alzheimer disease neuropathologic change (ADNC), Lewy body disease (LBD), vascular brain injury (VBI), and limbic-predominant age-related TDP43 encephalopathy neuropathologic change (LATE-NC). Using linear mixed-effects models, we examined trajectories of cognitive decline for ADNC alone compared to ADNC plus LBD, VBI, or LATE-NC. We also examined differences between observed trajectories …
Financial Toxicity And Cost-Related Imaging Nonadherence In Pediatric Outpatient Imaging, Shireen E Hayatghaibi, Gregory L Jordan, Tucker Hansen, Amy E Ensing, Aditi Gupta, Evan A Mihalakakos, Bin Zhang, Pradipta Debnath, Carrie C Coughlin
Financial Toxicity And Cost-Related Imaging Nonadherence In Pediatric Outpatient Imaging, Shireen E Hayatghaibi, Gregory L Jordan, Tucker Hansen, Amy E Ensing, Aditi Gupta, Evan A Mihalakakos, Bin Zhang, Pradipta Debnath, Carrie C Coughlin
2020-Current year OA Pubs
RATIONALE AND OBJECTIVES: Financial toxicity, defined as the financial burden and stress experienced due to medical costs, is increasingly recognized as a key patient-reported outcome and has been linked to cost-related non-adherence in adult populations. However, its prevalence and impact in pediatric imaging are unknown. We examined the prevalence and predictors of financial toxicity among families of children undergoing outpatient imaging and its association with imaging non-adherence.
MATERIALS AND METHODS: We conducted a prospective cross-sectional survey of parental caregivers of children (< 18 years of age) undergoing outpatient imaging at two free standing children's hospitals in the U.S. (July 2024-May 2025). Financial toxicity was measured using the adapted FACIT-COST instrument and scores < 26 indicated high financial toxicity. Multivariable logistic regression examined associations between family characteristics and high financial toxicity.
RESULTS: Among 399 caregivers, the mean FACIT-COST score was 24.6 (SD 10.2), and 49% were categorized as having …
Kirschner Wire Skeletal Fixation In The Hand And Wrist: Risk Of Infection And Predictors Of Progression To Major Complications, Mitchell S Mologne, Julia M Perugini, Nicholas A Calotta, Lindley B Wall, Charles A Goldfarb
Kirschner Wire Skeletal Fixation In The Hand And Wrist: Risk Of Infection And Predictors Of Progression To Major Complications, Mitchell S Mologne, Julia M Perugini, Nicholas A Calotta, Lindley B Wall, Charles A Goldfarb
2020-Current year OA Pubs
PURPOSE: Kirschner wire (K-wire) infections continue to be a challenge in hand surgery. Our purpose was to quantify the frequency of K-wire site infections of the hand and wrist, to tabulate major and minor infectious manifestations, to identify factors that may predispose a patient to major complications, and to generate an updated algorithm for prognostication and treatment of K-wire site infections.
METHODS: Patients treated with K-wires in the fingers, hand, and wrist who developed infections between 2018 and 2024 at our institution were identified. Information regarding patient factors, injury, treatment, and subsequent infectious complications was collected. Variables from single variable …
Achilles Tendon Injuries In Major League Soccer: A 10-Year Analysis Of Injury Rate, Return To Play, And Performance Metrics, Brian Forsythe, Catherine Hand, Francis Hand, Henry Eilen, Matthew Varano, Jared Sasaki, Camden Bohn, Anne Timmermann, Lauren Fertig, Eric Giza, Robert H Brophy, Bert Mandelbaum, Kirk Mccullough
Achilles Tendon Injuries In Major League Soccer: A 10-Year Analysis Of Injury Rate, Return To Play, And Performance Metrics, Brian Forsythe, Catherine Hand, Francis Hand, Henry Eilen, Matthew Varano, Jared Sasaki, Camden Bohn, Anne Timmermann, Lauren Fertig, Eric Giza, Robert H Brophy, Bert Mandelbaum, Kirk Mccullough
2020-Current year OA Pubs
BACKGROUND: Injuries to the Achilles tendon, such as tears or ruptures, are commonly observed among elite athletes. These injuries can be debilitating for professional soccer players, leading to prolonged recovery and potential performance declines.
PURPOSE: To investigate the annual incidence, return-to-play (RTP) duration, and postinjury performance outcomes of Major League Soccer (MLS) players who sustained Achilles tendon injuries from 2010 to 2021.
STUDY DESIGN: Cohort study; Level of evidence, 3.
METHODS: This retrospective matched-cohort study evaluated MLS players with Achilles tendon injuries from 2010 to 2021, identified through the MLS Injury Surveillance database, and compared outcomes, including RTP duration, between …
Language And Sound Exposure Across Neonatal Intensive Care Hospitalization And Relationships With Early Outcome, R Pineda, L J Woodward, Z A Vesoulis, C D Smyser, T E Inder, A M Mathur, B L Schlaggar
Language And Sound Exposure Across Neonatal Intensive Care Hospitalization And Relationships With Early Outcome, R Pineda, L J Woodward, Z A Vesoulis, C D Smyser, T E Inder, A M Mathur, B L Schlaggar
2020-Current year OA Pubs
OBJECTIVES: Examine relationships between quantitative measures of language and sound exposure in the NICU and infant neurobehavior.
STUDY DESIGN: Sixty-four preterm infants (≤28 weeks of gestation) had language and sound exposure measured across four time points: within two weeks of birth and at 30, 34, and 35-41 weeks postmenstrual age (PMA). Neurobehavior was assessed at 35-41 weeks PMA using the NICU Network Neurobehavioral Scales.
RESULTS: Higher average decibel levels in the NICU environment were associated with lower infant orientation scores (p = 0.04, β = -0.33). Higher peak decibel levels were associated with greater hypertonia (p = 0.01, β = …
A Multistate Analysis Of Longitudinal Care Outcomes Among People Newly Linked To Human Immunodeficiency Virus Care In Missouri, Aditi Ramakrishnan, Daniel Vo, Ernie-Paul Barrette, Rachel M Presti, William G Powderly, Anne Trolard, Corey Grejtak-Heaps, Elvin H Geng, Aaloke Mody, Lindsey M Filiatreau
A Multistate Analysis Of Longitudinal Care Outcomes Among People Newly Linked To Human Immunodeficiency Virus Care In Missouri, Aditi Ramakrishnan, Daniel Vo, Ernie-Paul Barrette, Rachel M Presti, William G Powderly, Anne Trolard, Corey Grejtak-Heaps, Elvin H Geng, Aaloke Mody, Lindsey M Filiatreau
2020-Current year OA Pubs
BACKGROUND: Advancing the HIV response in Missouri, an Ending the HIV Epidemic priority state, requires stronger characterization of treatment gaps. Routine cross-sectional reporting may fail to capture important gaps in care that longitudinal methods can reveal.
METHODS: We characterized clinic engagement and viral suppression among people with Human Immunodeficiency Virus (HIV) aged ≥18 years who were newly linked to clinic in St Louis, Missouri, between 1 January 2015 and 15 March 2020. Using multistate analytic methods that capture change over time, we estimated the prevalence of individuals in 9 mutually exclusive and exhaustive states over 3 years following linkage to …
Mll3 And Mll4 Sustain Hematopoietic Stem Cell Multipotency By Opposing A B-Cell Default State, Helen C Wang, Ran Chen, Wei Yang, Rohini Muthukumar, Tingting Hu, Riddhi M Patel, Emily B Casey, Elisabeth Denby, Run Zhang, Guojia Xie, Kai Ge, Grant A Challen, Jeffrey J Bednarski, Jeffrey A Magee
Mll3 And Mll4 Sustain Hematopoietic Stem Cell Multipotency By Opposing A B-Cell Default State, Helen C Wang, Ran Chen, Wei Yang, Rohini Muthukumar, Tingting Hu, Riddhi M Patel, Emily B Casey, Elisabeth Denby, Run Zhang, Guojia Xie, Kai Ge, Grant A Challen, Jeffrey J Bednarski, Jeffrey A Magee
2020-Current year OA Pubs
Hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) are sustained by networks of transcription factors and epigenetic regulators that prime lineage-specific programs yet maintain multipotency. Two epigenetic regulators, MLL3 and MLL4, play important but distinct roles in maintaining this balance. MLL3 promotes HSC differentiation, whereas MLL4 opposes differentiation. These activities are essential for both normal homeostasis and leukemia suppression, yet it is not clear how MLL3 and MLL4 regulate HSC and MPP gene expression to control HSC/MPP fate decisions. To resolve these mechanisms, we performed an extensive series of single-cell genomic studies after conditionally deleting Mll3, Mll4 or both genes …
Acute Opioid Responses Are Modulated By Dynamic Interactions Of Oprm1 And Fgf12, Paige M Lemen, Alexander S Hatoum, Arpana Agrawal, Et Al.
Acute Opioid Responses Are Modulated By Dynamic Interactions Of Oprm1 And Fgf12, Paige M Lemen, Alexander S Hatoum, Arpana Agrawal, Et Al.
2020-Current year OA Pubs
We generated time-series data for 105 morphine- and naloxone-related traits across ~700 BXD mice (64 diverse strains for both sexes) for 3 hr after a single morphine injection. Variations in responses were mapped using genome sequencing-based genotypes. The locomotor responses to morphine mapped to the µ opioid receptor gene (
Loss Of Nemp1 Disrupts Female Meiosis And Activates A Conserved Atm-Chk2 Checkpoint, Bilal Ahmad Hakim, Yonit Tsatskis, Ling Zhang, Esther Choi, Ying Zhang, Didier Hodzic, Que Wu, Muyun Zhang, Maryam Pashaei, Kyungwon Ha, Jannette Rusch, Julie A Brill, Miguel Angel Brieño-Enríquez, Andrea Jurisicova, Helen Mcneill
Loss Of Nemp1 Disrupts Female Meiosis And Activates A Conserved Atm-Chk2 Checkpoint, Bilal Ahmad Hakim, Yonit Tsatskis, Ling Zhang, Esther Choi, Ying Zhang, Didier Hodzic, Que Wu, Muyun Zhang, Maryam Pashaei, Kyungwon Ha, Jannette Rusch, Julie A Brill, Miguel Angel Brieño-Enríquez, Andrea Jurisicova, Helen Mcneill
2020-Current year OA Pubs
Female germ cells must preserve the integrity of their genome and generate genetic diversity via meiotic recombination. This challenging process is error prone. Highly conserved checkpoint pathways detect errors in recombination and DNA damage, inducing the death of defective oocytes. Nuclear Envelope Membrane Protein (NEMP) homologs are highly conserved proteins critical for fertility in flies, worms, fish and mice. They localize to the inner nuclear envelope where they provide mechanical support. However, why NEMP homologs are specifically required for fertility is still unclear. Using both Drosophila and mouse models, we establish that loss of NEMP homologs leads to activation of …
Performance Evaluation Of The Xpert® Hcv Test On Fingerstick Blood In A Prospective Observational Clinical Study At Clia-Waived Sites In The United States, Jennifer R Havens, L Madeline Mccrary, Et Al.
Performance Evaluation Of The Xpert® Hcv Test On Fingerstick Blood In A Prospective Observational Clinical Study At Clia-Waived Sites In The United States, Jennifer R Havens, L Madeline Mccrary, Et Al.
2020-Current year OA Pubs
BACKGROUND: A major barrier to hepatitis C virus (HCV) elimination in the United States is the lack of a point-of-care test to confirm the presence of HCV RNA. The purpose of this clinical trial was to evaluate the performance of the Xpert® HCV test at CLIA-waived sites in the United States.
METHODS: Participants at risk and/or with signs/symptoms of HCV infection provided fingerstick blood that was tested on the Xpert® HCV test and venous blood tested using the cobas® HCV and Elecsys® Anti-HCV II tests. Fingerstick blood was collected at CLIA-waived sites by individuals self-trained on collection procedures.
RESULTS: Participants …
The Best Of Both Worlds: How Combining A Large Language Model And A Rule-Based Algorithm Makes Catheter-Associated Urinary Tract Infection Surveillance More Efficient, Joshua Nordman, Claire Najjuuko, Nicholas Jeschke, Rachael E Snyders, Maria Cristina Vazquez Guillamet, Hilary Babcock, Patrick Reich, Andrew Atkinson, Jonas Marschall, Abby Sung, Et Al.
The Best Of Both Worlds: How Combining A Large Language Model And A Rule-Based Algorithm Makes Catheter-Associated Urinary Tract Infection Surveillance More Efficient, Joshua Nordman, Claire Najjuuko, Nicholas Jeschke, Rachael E Snyders, Maria Cristina Vazquez Guillamet, Hilary Babcock, Patrick Reich, Andrew Atkinson, Jonas Marschall, Abby Sung, Et Al.
2020-Current year OA Pubs
BACKGROUND: Catheter-associated urinary tract infection (CAUTI) surveillance is critical for patient safety. Many healthcare systems use electronic algorithms to flag candidate infection events but still require manual chart review to confirm CAUTI cases. We evaluated the use of a large language model (LLM) to enhance CAUTI surveillance.
METHODS: We analyzed 919 potential CAUTI cases flagged by the electronic surveillance algorithm at Barnes-Jewish Hospital from 2021 to 2024. These cases were previously classified as 291 CAUTIs and 628 non-CAUTIs by trained infection preventionists (IPs). Several approaches for applying the National Healthcare Safety Network (NHSN) CAUTI definition after extracting clinical data from …
Recent Advances In Alzheimer's Disease: From Molecular Mechanisms To Therapeutic Strategies, Michelle D Rudman, Jason D Ulrich, David M Holtzman
Recent Advances In Alzheimer's Disease: From Molecular Mechanisms To Therapeutic Strategies, Michelle D Rudman, Jason D Ulrich, David M Holtzman
2020-Current year OA Pubs
Alzheimer's disease (AD) remains the leading cause of dementia worldwide and an escalating global health crisis. The hallmark amyloid plaques and neurofibrillary tangles (NFT) are now known to be accompanied by a complex array of pathologies that culminate in neurodegeneration and cognitive decline. New disease-modifying therapies for AD can now slow cognitive decline through the removal of amyloid plaques from the brain, but treatments to stop or prevent cognitive impairment remain elusive. In this review, we summarize the most recent updates in AD research on pathologic disease mechanisms and therapeutic strategies, highlighting advancements in apolipoprotein E (APOE) biology, neuroimmunology, biomarker …
Tgf-Β Drives The Conversion Of Conventional Nk Cells Into Uterine Tissue-Resident Nk Cells To Support Murine Pregnancy, Josselyn D Barahona, Liping Yang, D Michael Nelson, Wayne M Yokoyama
Tgf-Β Drives The Conversion Of Conventional Nk Cells Into Uterine Tissue-Resident Nk Cells To Support Murine Pregnancy, Josselyn D Barahona, Liping Yang, D Michael Nelson, Wayne M Yokoyama
2020-Current year OA Pubs
Tissue microenvironments shape lymphocyte differentiation to align immune function with local physiological demands. Uterine natural killer (NK) cells are critical for reproductive success, yet the molecular cues in the uterus that instruct their specialized identities remain incompletely understood. Here, we identify a TGF-β-dependent differentiation pathway by which circulating conventional NK cells convert into uterine tissue-resident NK cells during murine pregnancy. Loss of TGF-β receptor II expression in
Trends In Lung Cancer Survival: Superior Outcomes In Us Veterans Compared With The General Population, Nikki E Rossetti, Brendan T Heiden, Steven Tohmasi, Nahom Seyoum, Theodore Thomas, Whitney S Brandt, Sara Malone, Yan Yan, Ana Baumann, Su-Hsin Chang, Daniel Kreisel, Ruben Nava, Bryan Meyers, Benjamin Kozower, Varun Puri, Et Al.
Trends In Lung Cancer Survival: Superior Outcomes In Us Veterans Compared With The General Population, Nikki E Rossetti, Brendan T Heiden, Steven Tohmasi, Nahom Seyoum, Theodore Thomas, Whitney S Brandt, Sara Malone, Yan Yan, Ana Baumann, Su-Hsin Chang, Daniel Kreisel, Ruben Nava, Bryan Meyers, Benjamin Kozower, Varun Puri, Et Al.
2020-Current year OA Pubs
BACKGROUND: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality in the United States, but survival outcomes are shifting with evolving therapies and screening. Recent findings suggest that survival improvements vary across health-care systems, with favorable trends observed in the Veterans Health Administration (VHA). We sought to compare NSCLC survival trends across US health systems.
METHODS: We conducted a retrospective cohort study of patients with NSCLC (2007-2019) using data from the VHA and the National Cancer Database (NCDB), representing the non-VHA US general population. The primary exposure was health system (VHA vs non-VHA), and the primary outcome …
Multiple Event Segmentation Mechanisms In The Human Brain, Tan T Nguyen, Joset A Etzel, Matthew A Bezdek, Jeffrey M Zacks
Multiple Event Segmentation Mechanisms In The Human Brain, Tan T Nguyen, Joset A Etzel, Matthew A Bezdek, Jeffrey M Zacks
2020-Current year OA Pubs
The human brain segments continuous experience into discrete events, with theoretical accounts proposing two distinct mechanisms: creating boundaries at points of high
Subunit Composition Of The Katp Channels That Modulate Contractility Of Skeletal Muscle During Fatigue, Rosa Scala, Yuezhou Chen, Berk Mizrak, Gretchen A Meyer, Colin G Nichols
Subunit Composition Of The Katp Channels That Modulate Contractility Of Skeletal Muscle During Fatigue, Rosa Scala, Yuezhou Chen, Berk Mizrak, Gretchen A Meyer, Colin G Nichols
2020-Current year OA Pubs
ATP-sensitive potassium (KATP) channels are among the most expressed ion channels in skeletal muscle sarcolemma. While all KATP subunits can be detected in skeletal muscles, transcripts are enriched for KCNJ11 and ABCC9, suggesting that noncanonical Kir6.2/SUR2A assembly may constitute the majority of sarcolemmal KATP channels, but there has been no systematic dissection of KATP makeup in skeletal muscles. Here, we used a unique collection of murine lines selectively lacking specific channel-forming subunits (knockout, KO), and combined a genetic and pharmacological approach to determine which subunits of KATP channels are functionally relevant for skeletal muscle contraction. Under fatiguing conditions, isometric tetanic …
Long-Term Inactivation Mediated By Different Fgf-A Homologues On Heterologously Expressed Nav1.2 Currents, Yenisleidy Lorenzo-Ceballos, Pedro L Martinez-Espinosa, Xiao-Ming Xia, Christopher J Lingle
Long-Term Inactivation Mediated By Different Fgf-A Homologues On Heterologously Expressed Nav1.2 Currents, Yenisleidy Lorenzo-Ceballos, Pedro L Martinez-Espinosa, Xiao-Ming Xia, Christopher J Lingle
2020-Current year OA Pubs
A-isoforms of cytosolic growth factor homologous factors (FGF11-14) mediate long-term inactivation (LTI) of voltage-dependent sodium (NaV) channels. LTI is a rapid onset process that is competitive with the fast inactivation (IF) intrinsic to NaV channels, with little or no interconversion between inactivated states. Since recovery from LTI is orders of magnitude slower than recovery from IF, repetitive depolarizations lead to use-dependent accumulation of NaV channels in slow recovery states, thereby limiting NaV availability during trains of action potentials. Of the two or more N-terminal splice variants of the various FGF homologues, LTI specifically arises only from the A-isoform of each …
A Conserved Mechanism For Dimerization And Activation Of Superfamily 1a Uvrd-Family Helicases, Binh Nguyen, Kacey N Mersch, Ankita Chadda, Eric A Galburt, Timothy M Lohman
A Conserved Mechanism For Dimerization And Activation Of Superfamily 1a Uvrd-Family Helicases, Binh Nguyen, Kacey N Mersch, Ankita Chadda, Eric A Galburt, Timothy M Lohman
2020-Current year OA Pubs
DNA helicases are ATP-dependent motor proteins that catalyze duplex DNA unwinding and are involved in DNA repair, recombination, and replication restart. Prominent members of the non-hexameric SF1A UvrD-family helicases are Escherichia coli UvrD, Rep, Bacillus stearothermophilus PcrA, and Mycobacterium tuberculosis (Mtb) UvrD1. SF1A monomers are processive 3'-to-5' single-stranded DNA translocases but need to be activated to become DNA helicases. One mechanism of activation is dimerization. Whereas Rep, UvrD, and PcrA form non-covalent dimers, the Mtb UvrD1 helicase forms a redox-dependent covalent dimer. Dimerization of Mtb UvrD1 occurs between the same regulatory domain (2B) within each subunit stabilized by a disulfide …
Extending The Fundamental Theorem Of Biomedical Informatics For The Ai Era, Philip R O Payne, Jonathan H Chen, Christopher A Longhurst
Extending The Fundamental Theorem Of Biomedical Informatics For The Ai Era, Philip R O Payne, Jonathan H Chen, Christopher A Longhurst
2020-Current year OA Pubs
BACKGROUND: Charles Friedman's Fundamental Theorem of Biomedical Informatics holds that a person working in partnership with an information resource outperforms that same person unassisted. Since its publication, advances in artificial intelligence (AI), adaptive learning systems, and large-scale data infrastructures have transformed the biomedical ecosystem, extending informatics beyond clinical care into domains such as public health, consumer health, translational science, and the broader life sciences. Such expansion has further underscored the importance of the Fundamental Theorem while also elucidating ways it can be expanded to meet current needs.
OBJECTIVE: To reassess and extend the Fundamental Theorem for the AI era in …
Multi-Center Comparison Of Corticotropin Releasing Hormone Vs. Desmopressin Stimulation Responses In Inferior Petrosal Sinus Sampling For Cushing's Disease, Samuel A Tenhoeve, Julie M Silverstein, Albert H Kim, Et Al.
Multi-Center Comparison Of Corticotropin Releasing Hormone Vs. Desmopressin Stimulation Responses In Inferior Petrosal Sinus Sampling For Cushing's Disease, Samuel A Tenhoeve, Julie M Silverstein, Albert H Kim, Et Al.
2020-Current year OA Pubs
OBJECTIVES: Inferior petrosal sinus sampling (IPSS) is important for confirming Cushing's Disease (CD). Due to lack of corticotropin releasing hormone (CRH) availability, desmopressin/DDAVP is being used as the alternative stimulating agent but has limited data regarding testing cutoffs.
DESIGN: We compared the stimulation profiles of desmopressin and CRH in patients with CD.
METHODS: Data from the multi-center Registry of Adenomas of the PItuitary and Related Disorders (RAPID) was evaluated. 93 patients with CD confirmed by pathology or biochemical remission that underwent IPSS testing prior to surgical resection (desmopressin [n = 57], CRH [n = 36] or both [n = 1]). …
A Call To Investigate The Association Between Histoplasmosis And Fatigue, Christian Hendrix, Julio Zuniga-Moya, Andrej Spec, Patrick Mazi
A Call To Investigate The Association Between Histoplasmosis And Fatigue, Christian Hendrix, Julio Zuniga-Moya, Andrej Spec, Patrick Mazi
2020-Current year OA Pubs
Historically, infections are subjectively associated with fatigue, a common yet poorly delineated syndrome. The impact on patient quality of life is the ultimate justification to evaluate fatigue in patients with infections. While fungal infections are subjectively associated with fatigue, there are minimal quantifiable fungal research outcomes that evaluate histoplasmosis and fatigue.
Evaluation Of The Impact Of A Pathology Trainee-Driven Manual Review Process For Reference Testing At A Large Academic Center, Carly Maucione, Christopher W Farnsworth, Mark A Zaydman
Evaluation Of The Impact Of A Pathology Trainee-Driven Manual Review Process For Reference Testing At A Large Academic Center, Carly Maucione, Christopher W Farnsworth, Mark A Zaydman
2020-Current year OA Pubs
BACKGROUND: Increasing reliance on and complexity of laboratory testing necessitates laboratory stewardship initiatives to ensure appropriate test ordering, especially as reference testing costs continue to rise. Prospective manual review processes, although demanding of resources, have been shown to be cost-effective, but literature addressing the value of such a process is lacking.
METHODS: The pathology trainee-driven manual review process of 444 chemistry and microbiology tests on approval at a large academic center was reviewed. Data were extracted from an internal-use call-log and analyzed for test volumes, cancellation rates, and cost savings. A hypergeometric distribution was used to model random variation in …
Modern Molecular Profiling Recontextualizes The Nrg/Rtog 0539 Trial And Reveals Hidden High-Risk And Radiotherapy-Resistant Meningiomas, Leeor S Yefet, Clifford Robinson, Et Al.
Modern Molecular Profiling Recontextualizes The Nrg/Rtog 0539 Trial And Reveals Hidden High-Risk And Radiotherapy-Resistant Meningiomas, Leeor S Yefet, Clifford Robinson, Et Al.
2020-Current year OA Pubs
BACKGROUND: Meningiomas exhibit clinical heterogeneity. Radiotherapy (RT) remains the only adjuvant therapy, but tumor-control is variable, and biomarkers are limited. NRG/RTOG-0539 is the first prospective phase 2 trial to stratify meningioma patients for adjuvant RT based on clinical risk. Here, we apply modern molecular tools to this cohort and identify correlates of RT response.
METHODS: Tumor tissue from 100 RTOG-0539 patients was profiled using DNA methylation arrays, RNA sequencing, and whole-exome sequencing. Recurrence scores, Molecular Groups, gene expression, and copy number alterations were compared across clinical groups and between RT responders and non-responders; non-response was defined as progression or death …
Delayed Diagnosis Of A Rare Metabolic Disorder In Adulthood, Isaiah K Mensah, Angie Carreno Martinez, Taylor Wilson, Miguel Valdez, Maria Laura Duque Lasio
Delayed Diagnosis Of A Rare Metabolic Disorder In Adulthood, Isaiah K Mensah, Angie Carreno Martinez, Taylor Wilson, Miguel Valdez, Maria Laura Duque Lasio
2020-Current year OA Pubs
No abstract provided.
Laser Interstitial Thermal Therapy Enhances Bidirectional Blood-Brain Barrier Permeability In Glioblastoma, Ryan T Cleary, Yiwei Fu, David Giles, Jinyun Yuan, Diogo P Moniz Garcia, Danny Palmer, Rowland H Han, Timothy Woodiwiss, Alicia B Yang, Dimitrios Mathios, Hong Chen, Albert H Kim
Laser Interstitial Thermal Therapy Enhances Bidirectional Blood-Brain Barrier Permeability In Glioblastoma, Ryan T Cleary, Yiwei Fu, David Giles, Jinyun Yuan, Diogo P Moniz Garcia, Danny Palmer, Rowland H Han, Timothy Woodiwiss, Alicia B Yang, Dimitrios Mathios, Hong Chen, Albert H Kim
2020-Current year OA Pubs
BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for glioblastoma that increases blood-brain barrier (BBB) permeability. However, the mechanisms and spatiotemporal features of this effect remain unclear. It is also unknown whether LITT promotes release of circulating tumor DNA (ctDNA).
METHODS: Using our previously developed LITT mouse model, we employed single-cell RNA-sequencing (scRNA-seq) to investigate gene expression changes in endothelial cells following LITT in the naive mouse brain. Brains were also harvested at multiple time points to assess LITT effects on tight junction (TJ) integrity and transcytosis via immunofluorescence and transmission electron microscopy. Human glioblastoma tissues were …