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Full-Text Articles in Medicine and Health Sciences

An Iron-Rich Subset Of Macrophages Promotes Tumor Growth Through A Bach1-Ednrb Axis, Ian W Folkert, Mai T Dang, Et Al. Oct 2024

An Iron-Rich Subset Of Macrophages Promotes Tumor Growth Through A Bach1-Ednrb Axis, Ian W Folkert, Mai T Dang, Et Al.

2020-Current year OA Pubs

We define a subset of macrophages in the tumor microenvironment characterized by high intracellular iron and enrichment of heme and iron metabolism genes. These iron-rich tumor-associated macrophages (iTAMs) supported angiogenesis and immunosuppression in the tumor microenvironment and were conserved between mice and humans. iTAMs comprise two additional subsets based on gene expression profile and location-perivascular (pviTAM) and stromal (stiTAM). We identified the endothelin receptor type B (Ednrb) as a specific marker of iTAMs and found myeloid-specific deletion of Ednrb to reduce tumor growth and vascular density. Further studies identified the transcription factor Bach1 as a repressor of the iTAM transcriptional …


Machine Learning And Bayesian Network Analyses Identifies Associations With Insomnia In A National Sample Of 31,285 Treatment-Seeking College Students, Adam Calderon, Seung Yeon Baik, Matthew H S Ng, Ellen E Fitzsimmons-Craft, Daniel Eisenberg, Denise E Wilfley, C Barr Taylor, Michelle G Newman Oct 2024

Machine Learning And Bayesian Network Analyses Identifies Associations With Insomnia In A National Sample Of 31,285 Treatment-Seeking College Students, Adam Calderon, Seung Yeon Baik, Matthew H S Ng, Ellen E Fitzsimmons-Craft, Daniel Eisenberg, Denise E Wilfley, C Barr Taylor, Michelle G Newman

2020-Current year OA Pubs

BACKGROUND: A better understanding of the relationships between insomnia and anxiety, mood, eating, and alcohol-use disorders is needed given its prevalence among young adults. Supervised machine learning provides the ability to evaluate which mental disorder is most associated with heightened insomnia among U.S. college students. Combined with Bayesian network analysis, probable directional relationships between insomnia and interacting symptoms may be illuminated.

METHODS: The current exploratory analyses utilized a national sample of college students across 26 U.S. colleges and universities collected during population-level screening before entering a randomized controlled trial. We used a 4-step statistical approach: (1) at the disorder level, …


25-Hydroxycholesterol Promotes Brain Cytokine Production And Leukocyte Infiltration In A Mouse Model Of Lipopolysaccharide-Induced Neuroinflammation, Johnathan Romero, Danira Toral-Rios, Jinsheng Yu, Steven M Paul, Anil G Cashikar Oct 2024

25-Hydroxycholesterol Promotes Brain Cytokine Production And Leukocyte Infiltration In A Mouse Model Of Lipopolysaccharide-Induced Neuroinflammation, Johnathan Romero, Danira Toral-Rios, Jinsheng Yu, Steven M Paul, Anil G Cashikar

2020-Current year OA Pubs

Neuroinflammation has been implicated in the pathogenesis of several neurologic and psychiatric disorders. Microglia are key drivers of neuroinflammation and, in response to different inflammatory stimuli, overexpress a proinflammatory signature of genes. Among these, Ch25h is a gene overexpressed in brain tissue from Alzheimer's disease as well as various mouse models of neuroinflammation. Ch25h encodes cholesterol 25-hydroxylase, an enzyme upregulated in activated microglia under conditions of neuroinflammation, that hydroxylates cholesterol to form 25-hydroxycholesterol (25HC). 25HC can be further metabolized to 7α,25-dihydroxycholesterol, which is a potent chemoattractant of leukocytes. We have previously shown that 25HC increases the production and secretion of …


Genetic And Clinical Correlates Of Two Neuroanatomical Ai Dimensions In The Alzheimer's Disease Continuum, Junhao Wen, Aristeidis Sotiras, Daniel S Marcus, Pamela Lamontagne, Tammie L Benzinger, John C Morris, Et Al. Oct 2024

Genetic And Clinical Correlates Of Two Neuroanatomical Ai Dimensions In The Alzheimer's Disease Continuum, Junhao Wen, Aristeidis Sotiras, Daniel S Marcus, Pamela Lamontagne, Tammie L Benzinger, John C Morris, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) is associated with heterogeneous atrophy patterns. We employed a semi-supervised representation learning technique known as Surreal-GAN, through which we identified two latent dimensional representations of brain atrophy in symptomatic mild cognitive impairment (MCI) and AD patients: the "diffuse-AD" (R1) dimension shows widespread brain atrophy, and the "MTL-AD" (R2) dimension displays focal medial temporal lobe (MTL) atrophy. Critically, only R2 was associated with widely known sporadic AD genetic risk factors (e.g., APOE ε4) in MCI and AD patients at baseline. We then independently detected the presence of the two dimensions in the early stages by deploying the trained …


Cell Type-Specific Epigenetic Priming Of Gene Expression In Nucleus Accumbens By Cocaine, Philipp Mews, Yentl Van Der Zee, Ashik Gurung, Molly Estill, Rita Futamura, Hope Kronman, Aarthi Ramakrishnan, Meagan Ryan, Abner A Reyes, Benjamin A Garcia, Caleb J Browne, Simone Sidoli, Li Shen, Eric J Nestler Oct 2024

Cell Type-Specific Epigenetic Priming Of Gene Expression In Nucleus Accumbens By Cocaine, Philipp Mews, Yentl Van Der Zee, Ashik Gurung, Molly Estill, Rita Futamura, Hope Kronman, Aarthi Ramakrishnan, Meagan Ryan, Abner A Reyes, Benjamin A Garcia, Caleb J Browne, Simone Sidoli, Li Shen, Eric J Nestler

2020-Current year OA Pubs

A hallmark of addiction is the ability of drugs of abuse to trigger relapse after periods of prolonged abstinence. Here, we describe an epigenetic mechanism whereby chronic cocaine exposure causes lasting chromatin and downstream transcriptional modifications in the nucleus accumbens (NAc), a critical brain region controlling motivation. We link prolonged withdrawal from cocaine to the depletion of the histone variant H2A.Z, coupled with increased genome accessibility and latent priming of gene transcription, in D1 dopamine receptor-expressing medium spiny neurons (D1 MSNs) that relate to aberrant gene expression upon drug relapse. The histone chaperone ANP32E removes H2A.Z from chromatin, and we …


A New Era Of Data-Driven Cancer Research And Care: Opportunities And Challenges, Felicia Gomez, Arpad M Danos, Joshua F Mcmichael, Malachi Griffith, Obi L Griffith, Et Al. Oct 2024

A New Era Of Data-Driven Cancer Research And Care: Opportunities And Challenges, Felicia Gomez, Arpad M Danos, Joshua F Mcmichael, Malachi Griffith, Obi L Griffith, Et Al.

2020-Current year OA Pubs

People diagnosed with cancer and their formal and informal caregivers are increasingly faced with a deluge of complex information, thanks to rapid advancements in the type and volume of diagnostic, prognostic, and treatment data. This commentary discusses the opportunities and challenges that the society faces as we integrate large volumes of data into regular cancer care.


Distinct Visual Processing Networks For Foveal And Peripheral Visual Fields, Jie Zhang, Huihui Zhou, Shuo Wang Oct 2024

Distinct Visual Processing Networks For Foveal And Peripheral Visual Fields, Jie Zhang, Huihui Zhou, Shuo Wang

2020-Current year OA Pubs

Foveal and peripheral vision are two distinct modes of visual processing essential for navigating the world. However, it remains unclear if they engage different neural mechanisms and circuits within the visual attentional system. Here, we trained macaques to perform a free-gaze visual search task using natural face and object stimuli and recorded a large number of 14588 visually responsive units from a broadly distributed network of brain regions involved in visual attentional processing. Foveal and peripheral units had substantially different proportions across brain regions and exhibited systematic differences in encoding visual information and visual attention. The spike-local field potential (LFP) …


Nationwide Availability Of And Enrollment In Medicare And Medicaid Dual-Eligible Special Needs Plans With Exclusively Aligned Enrollment, Kenton J Johnston, Michelle Hendricks, Megha Dabas, Eliza Macneal, Jeah Jung, David J Meyers, Jose F Figueroa, Eric T Roberts Oct 2024

Nationwide Availability Of And Enrollment In Medicare And Medicaid Dual-Eligible Special Needs Plans With Exclusively Aligned Enrollment, Kenton J Johnston, Michelle Hendricks, Megha Dabas, Eliza Macneal, Jeah Jung, David J Meyers, Jose F Figueroa, Eric T Roberts

2020-Current year OA Pubs

IMPORTANCE: In 2021, the Centers for Medicare & Medicaid Services designated a new category of dual-eligible special needs plans (D-SNPs) with exclusively aligned enrollment (receive Medicare and Medicaid benefits through the same plan or affiliated plans within the same organization).

OBJECTIVE: To assess the availability of and enrollment in D-SNPs with exclusively aligned enrollment and to compare the characteristics of beneficiaries enrolled in D-SNPs with exclusively aligned enrollment available vs beneficiaries without such enrollment available.

DESIGN, SETTING, AND PARTICIPANTS: Full-benefit beneficiaries enrolled in D-SNPs for 6 months or longer in 2021 or 2022. Availability of and beneficiary enrollment in D-SNPs …


Tirzepatide Prescribing Practices And Efficacy In Patients With Diabetes And Chronic Kidney Disease At A Large Tertiary Care Center In The United States, Sriya Amruta Kosaraju, Rong M Zhang Oct 2024

Tirzepatide Prescribing Practices And Efficacy In Patients With Diabetes And Chronic Kidney Disease At A Large Tertiary Care Center In The United States, Sriya Amruta Kosaraju, Rong M Zhang

2020-Current year OA Pubs

PURPOSE: Chronic kidney disease is a frequent complication of diabetes mellitus. Tirzepatide is the first dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for glycemic control in patients with type 2 diabetes. We present the efficacy and prescribing practices of tirzepatide in a cohort with diabetes and chronic kidney disease in a large tertiary care setting.

METHODS: We retrospectively identified new outpatient tirzepatide prescriptions in adults ≥18 years with diabetes and chronic kidney disease stages 1-5 from 2022 to 2023 across the Barnes Jewish Hospital system (St Louis, Missouri).

RESULTS: We identified 102 subjects with chronic kidney disease …


"I Just Had To Do What I Had To Do": Characterizing Direct And Indirect Prostate Cancer Treatment Costs For Black Survivors And Their Caregivers, Hannah E Rice, Allison J L'Hotta, Amela Siječić, Bettina F Drake, Su-Hsin Chang, Eric H Kim, Robin Wright-Jones, Mellve Shahid, Camille Neal, Ashley J Housten Oct 2024

"I Just Had To Do What I Had To Do": Characterizing Direct And Indirect Prostate Cancer Treatment Costs For Black Survivors And Their Caregivers, Hannah E Rice, Allison J L'Hotta, Amela Siječić, Bettina F Drake, Su-Hsin Chang, Eric H Kim, Robin Wright-Jones, Mellve Shahid, Camille Neal, Ashley J Housten

2020-Current year OA Pubs

UNLABELLED:

HIGHLIGHTS: Direct and indirect costs have a wide-ranging impact on the material, behavioral, and psychosocial aspects of financial well-being of Black prostate cancer survivors and their caregivers.These results emphasize the need for sharing cost information to support medical decision making.Future research should focus on the design of cost-sharing interventions that target the complexities of direct and indirect costs collectively, rather than separately.


Corticosteroid Burst Therapy In Patients With Acute Heart Failure: Design Of The Cortahf Pilot Study, Gad Cotter, Douglas L Mann, Et Al. Oct 2024

Corticosteroid Burst Therapy In Patients With Acute Heart Failure: Design Of The Cortahf Pilot Study, Gad Cotter, Douglas L Mann, Et Al.

2020-Current year OA Pubs

AIMS: Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID-19. Our hypothesis is that in patients with AHF and elevated C-reactive protein (CRP) levels without symptoms or signs of infection, a 7-day course of steroid therapy will lead to reduced inflammation and short-term improvement in quality …


Endosomal Fusion Of Ph-Dependent Enveloped Viruses Requires Ion Channel Trpm7, Catherine A Doyle, Marta E Stremska, Louis-Marie Bloyet, Cassandra E Thompson, Paul W Rothlauf, Sean P J Whelan, Et Al. Oct 2024

Endosomal Fusion Of Ph-Dependent Enveloped Viruses Requires Ion Channel Trpm7, Catherine A Doyle, Marta E Stremska, Louis-Marie Bloyet, Cassandra E Thompson, Paul W Rothlauf, Sean P J Whelan, Et Al.

2020-Current year OA Pubs

The majority of viruses classified as pandemic threats are enveloped viruses which enter the cell through receptor-mediated endocytosis and take advantage of endosomal acidification to activate their fusion machinery. Here we report that the endosomal fusion of low pH-requiring viruses is highly dependent on TRPM7, a widely expressed TRP channel that is located on the plasma membrane and in intracellular vesicles. Using several viral infection systems expressing the envelope glycoproteins of various viruses, we find that loss of TRPM7 protects cells from infection by Lassa, LCMV, Ebola, Influenza, MERS, SARS-CoV-1, and SARS-CoV-2. TRPM7 ion channel activity is intrinsically necessary to …


Postprostatectomy Radiotherapy Timing And Long-Term Health-Related Quality Of Life, Sagar A Patel, Jeff M Michalski, Et Al. Oct 2024

Postprostatectomy Radiotherapy Timing And Long-Term Health-Related Quality Of Life, Sagar A Patel, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The association between radiotherapy (RT) timing after radical prostatectomy and long-term patient-reported health-related quality of life (HRQOL) in men with prostate cancer is unknown.

OBJECTIVE: To measure long-term HRQOL in men with prostate cancer up to 15 years after prostatectomy with or without RT and examine whether early vs late postprostatectomy RT is associated with differences in sexual, urinary, and bowel HRQOL.

DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter, longitudinal cohort analysis using HRQOL data from the PROST-QA (2003-2006) and RP2 consortium (2010-2013) studies was conducted. Men with localized prostate cancer undergoing radical prostatectomy were included. Data were analyzed …


Himal: Multimodal Hierarchical Multi-Task Auxiliary Learning Framework For Predicting Alzheimer's Disease Progression, Sayantan Kumar, Sean C Yu, Andrew Michelson, Thomas Kannampallil, Philip R O Payne Oct 2024

Himal: Multimodal Hierarchical Multi-Task Auxiliary Learning Framework For Predicting Alzheimer's Disease Progression, Sayantan Kumar, Sean C Yu, Andrew Michelson, Thomas Kannampallil, Philip R O Payne

2020-Current year OA Pubs

OBJECTIVE: We aimed to develop and validate a novel multimodal framework

MATERIALS AND METHODS: HiMAL utilized multimodal longitudinal visit data including imaging features, cognitive assessment scores, and clinical variables from MCI patients in the Alzheimer's Disease Neuroimaging Initiative dataset, to predict at each visit if an MCI patient will progress to AD within the next 6 months. Performance of HiMAL was compared with state-of-the-art single-task and multitask baselines using area under the receiver operator curve (AUROC) and precision recall curve (AUPRC) metrics. An ablation study was performed to assess the impact of each input modality on model performance. Additionally, longitudinal …


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 Oct 2024

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 …


Impacts Of Employment Status, Partnership, Cancer Type, And Surgical Treatment On Health-Related Quality Of Life In Irradiated Head And Neck Cancer Survivors, Ching-Rong Lin, Tsung-Min Hung, Eric Yi-Liang Shen, Ann-Joy Cheng, Po-Hung Chang, Shiang-Fu Huang, Chung-Jan Kang, Tuan-Jen Fang, Li-Ang Lee, Chih-Hung Chang, Joseph Tung-Chieh Chang Oct 2024

Impacts Of Employment Status, Partnership, Cancer Type, And Surgical Treatment On Health-Related Quality Of Life In Irradiated Head And Neck Cancer Survivors, Ching-Rong Lin, Tsung-Min Hung, Eric Yi-Liang Shen, Ann-Joy Cheng, Po-Hung Chang, Shiang-Fu Huang, Chung-Jan Kang, Tuan-Jen Fang, Li-Ang Lee, Chih-Hung Chang, Joseph Tung-Chieh Chang

2020-Current year OA Pubs

No abstract provided.


Integrating Audiovisual Immersion Into Pediatric Radiation Therapy Across Multiple Centers: Methodology, Timeliness, And Cost Of The Audiovisual-Assisted Therapeutic Ambience In Radiation Therapy Prospective Multi-Institutional Trial, Justin Oh, Stephanie M Perkins, Et Al. Oct 2024

Integrating Audiovisual Immersion Into Pediatric Radiation Therapy Across Multiple Centers: Methodology, Timeliness, And Cost Of The Audiovisual-Assisted Therapeutic Ambience In Radiation Therapy Prospective Multi-Institutional Trial, Justin Oh, Stephanie M Perkins, Et Al.

2020-Current year OA Pubs

PURPOSE: The Audiovisual-Assisted Therapeutic Ambience in Radiotherapy (AVATAR) trial was a prospective multicenter study (NCT03991156) examining the combination of video immersion with radiation therapy and was successfully conducted through the collaboration of pediatric radiation oncology teams at 10 institutions independent of any pre-existing consortium. We sought to analyze and report the methodology of trial conception and development, process map, and cost.

METHODS AND MATERIALS: The study enrolled patients aged 3 to 10 years preparing to undergo radiation therapy, integrated the combination of AVATAR-based video immersion with radiation therapy at each institution, and offered AVATAR use as an alternative to anesthesia, …


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. Oct 2024

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: …


Dcrm 2.0: Multispecialty Practice Recommendations For The Management Of Diabetes, Cardiorenal, And Metabolic Diseases, Yehuda Handelsman, Samuel Klein, Et Al. Oct 2024

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 …


Clinical And Research Application Of Fluid Biomarkers In Autosomal Dominant Alzheimer's Disease And Down Syndrome, María Carmona-Iragui, Antoinette O'Connor, Jorge Llibre-Guerra, Patrick Lao, Nicholas J Ashton, Juan Fortea, Raquel Sánchez-Valle Oct 2024

Clinical And Research Application Of Fluid Biomarkers In Autosomal Dominant Alzheimer's Disease And Down Syndrome, María Carmona-Iragui, Antoinette O'Connor, Jorge Llibre-Guerra, Patrick Lao, Nicholas J Ashton, Juan Fortea, Raquel Sánchez-Valle

2020-Current year OA Pubs

Autosomal dominant Alzheimer's disease (ADAD) and Down syndrome (DS) constitute genetic forms of Alzheimer's disease (AD). The study of these forms has been crucial in understanding the biomarker changes and disease progression, notably in advancing our knowledge of the natural history of AD. However, some specific characteristics of biomarkers in genetically determined forms and, most importantly, the near full penetrance and predictability of disease onset lead to a very different context of use for biomarkers in these populations. This article delves into the similarities and differences in biomarker profiles between genetically determined AD and sporadic cases, discussing the implications for …


Three Classes Of Propofol Binding Sites On Gabaa Receptors, Zi-Wei Chen, Satyanarayana M Chintala, John Bracamontes, Yusuke Sugasawa, Spencer R Pierce, Balazs R Varga, Edward H Smith, Christopher J Edge, Nicholas P Franks, Wayland W L Cheng, Gustav Akk, Alex S Evers Oct 2024

Three Classes Of Propofol Binding Sites On Gabaa Receptors, Zi-Wei Chen, Satyanarayana M Chintala, John Bracamontes, Yusuke Sugasawa, Spencer R Pierce, Balazs R Varga, Edward H Smith, Christopher J Edge, Nicholas P Franks, Wayland W L Cheng, Gustav Akk, Alex S Evers

2020-Current year OA Pubs

Propofol is a widely used anesthetic and sedative that acts as a positive allosteric modulator of gamma-aminobutyric acid type A (GABA


New Insights Into Innate Immunity In Alzheimer's Disease: From Apoe Protective Variants To Therapies, Yun Chen, David M Holtzman Oct 2024

New Insights Into Innate Immunity In Alzheimer's Disease: From Apoe Protective Variants To Therapies, Yun Chen, David M Holtzman

2020-Current year OA Pubs

Recent discoveries of rare variants of human APOE may shed light on novel therapeutic strategies for Alzheimer's disease (AD). Here, we highlight the newly identified protective variant [APOE3 Christchurch (APOE3ch, R136S)] as an example. We summarize human AD and mouse amyloidosis and tauopathy studies from the past 5 years that have been associated with this R136S variant. We also propose a potential mechanism for how this point mutation might lead to protection against AD pathology, from the molecular level, to cells, to mouse models, and potentially, to humans. Lastly, we extend our discussion of the recent insights gained regarding different …


Prophylactic Antibiotics For Excision Of Premalignant Vulvar Lesions: A Pilot Randomized Controlled Trial, Mary M Mullen, Whitney R Grither, Hannah Millimet, David G Mutch, Andrea R Hagemann, Carolyn K Mccourt, Matthew A Powell, Premal H Thaker, Dineo Khabele, Lindsay M Kuroki Oct 2024

Prophylactic Antibiotics For Excision Of Premalignant Vulvar Lesions: A Pilot Randomized Controlled Trial, Mary M Mullen, Whitney R Grither, Hannah Millimet, David G Mutch, Andrea R Hagemann, Carolyn K Mccourt, Matthew A Powell, Premal H Thaker, Dineo Khabele, Lindsay M Kuroki

2020-Current year OA Pubs

No prospective data have been described to inform guidelines on antibiotic prophylaxis for partial vulvectomies. Thus, we conducted a single-center, pilot, double-blind randomized controlled trial to assess the effectiveness of prophylactic antibiotics to prevent wound complications after partial vulvectomies. Patients were randomly assigned 1:1 to preoperative antibiotics or no preoperative antibiotics. The primary outcome of 30-day postoperative wound complications occurred in 31 (62 %) of all patients, with no differences between groups. The most common wound complications were superficial separation (54.2 % antibiotic prophylaxis vs. 65.3 % no prophylaxis, p = 0.37) and surgical site infection (0 % antibiotic prophylaxis …


The Dallas Donation After Circulatory Death Transplantation Summit: Expanding Donation After Circulatory Death Procedures Through Process Improvement, Broader Utilization, And Innovation, Michele Finotti, William C. Chapman, Et Al. Oct 2024

The Dallas Donation After Circulatory Death Transplantation Summit: Expanding Donation After Circulatory Death Procedures Through Process Improvement, Broader Utilization, And Innovation, Michele Finotti, William C. Chapman, Et Al.

2020-Current year OA Pubs

Despite a significant increase in utilization over the past decade, the number of donation after circulatory death (DCD) organs that are procured and transplanted in the United States (US) remains well below its potential. There is still room for expansion, as utilizing DCD organs to the fullest extent is currently the most viable solution to the persistent mismatch between supply and demand in transplantation. We convened a multidisciplinary transplantation summit to examine various aspects of DCD, with faculty members from around the world with clinical and academic interest in DCD donation and transplantation, including abdominal and cardiothoracic surgeons, organ procurement …


Discovery Of Genomic And Transcriptomic Pleiotropy Between Kidney Function And Soluble Receptor For Advanced Glycation End Products Using Correlated Meta-Analyses: The Long Life Family Study, Mary F Feitosa, Shiow J Lin, Sandeep Acharya, Bharat Thyagarajan, Mary K Wojczynski, Allison L Kuipers, Alexander Kulminski, Kaare Christensen, Joseph M Zmuda, Michael R Brent, Michael A Province Oct 2024

Discovery Of Genomic And Transcriptomic Pleiotropy Between Kidney Function And Soluble Receptor For Advanced Glycation End Products Using Correlated Meta-Analyses: The Long Life Family Study, Mary F Feitosa, Shiow J Lin, Sandeep Acharya, Bharat Thyagarajan, Mary K Wojczynski, Allison L Kuipers, Alexander Kulminski, Kaare Christensen, Joseph M Zmuda, Michael R Brent, Michael A Province

2020-Current year OA Pubs

Patients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end-products (AGEs). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration rate (eGFR) levels are associated with CKD and aging. We evaluated whether eGFR calculated from creatinine and cystatin C share pleiotropic genetic factors with sRAGE. We employed whole-genome sequencing and correlated meta-analyses on combined genome-wide association study (GWAS) p-values in 4182 individuals (age range: 24-110) from the Long Life Family Study (LLFS). We also conducted transcriptome-wide association studies (TWAS) on whole blood in a subset of …


A Modular Chemigenetic Calcium Indicator For Multiplexed In Vivo Functional Imaging, Helen Farrants, Christian Monroy Hernandez, Yao Chen, Et Al. Oct 2024

A Modular Chemigenetic Calcium Indicator For Multiplexed In Vivo Functional Imaging, Helen Farrants, Christian Monroy Hernandez, Yao Chen, Et Al.

2020-Current year OA Pubs

Genetically encoded fluorescent calcium indicators allow cellular-resolution recording of physiology. However, bright, genetically targetable indicators that can be multiplexed with existing tools in vivo are needed for simultaneous imaging of multiple signals. Here we describe WHaloCaMP, a modular chemigenetic calcium indicator built from bright dye-ligands and protein sensor domains. Fluorescence change in WHaloCaMP results from reversible quenching of the bound dye via a strategically placed tryptophan. WHaloCaMP is compatible with rhodamine dye-ligands that fluoresce from green to near-infrared, including several that efficiently label the brain in animals. When bound to a near-infrared dye-ligand, WHaloCaMP shows a 7× increase in fluorescence …


Ms Treatment De-Escalation: Review And Commentary, Krzysztof Selmaj, Hans-Peter Hartung, Marcin P Mycko, Igor Selmaj, Anne H Cross Oct 2024

Ms Treatment De-Escalation: Review And Commentary, Krzysztof Selmaj, Hans-Peter Hartung, Marcin P Mycko, Igor Selmaj, Anne H Cross

2020-Current year OA Pubs

Almost all currently licensed disease-modifying therapies (DMTs) for MS treatment require prolonged if not lifelong administration. Yet, as people age, the immune system has increasingly reduced responsiveness, known as immunosenescence. Many MS DMTs reduce the responsiveness of the immune system, increasing the risks for infections and possibly cancers. As people with MS (pwMS) age, it is recognized that inflammatory MS activity declines. Several studies have addressed de-escalation of DMTs for relapsing MS under special circumstances. Here, we review evidence for de-escalating DMTs as a strategy that is particularly relevant to pwMS of older age. Treatment de-escalation can involve various strategies, …


Type I Ifn Signaling In The Absence Of Irgm1 Promotes M. Tuberculosis Replication In Immune Cells By Suppressing T Cell Responses, Sumanta K Naik, Michael E Mcnehlan, Yassin Mreyoud, Rachel L Kinsella, Asya Smirnov, Chanchal Sur Chowdhury, Samuel R Mckee, Neha Dubey, Reilly Woodson, Darren Kreamalmeyer, Christina L Stallings Oct 2024

Type I Ifn Signaling In The Absence Of Irgm1 Promotes M. Tuberculosis Replication In Immune Cells By Suppressing T Cell Responses, Sumanta K Naik, Michael E Mcnehlan, Yassin Mreyoud, Rachel L Kinsella, Asya Smirnov, Chanchal Sur Chowdhury, Samuel R Mckee, Neha Dubey, Reilly Woodson, Darren Kreamalmeyer, Christina L Stallings

2020-Current year OA Pubs

Polymorphisms in the IRGM gene are associated with susceptibility to tuberculosis in humans. A murine ortholog of Irgm, Irgm1, is also essential for controlling Mycobacterium tuberculosis (Mtb) infection in mice. Multiple processes have been associated with IRGM1 activity that could impact the host response to Mtb infection, including roles in autophagy-mediated pathogen clearance and expansion of activated T cells. However, what IRGM1-mediated pathway is necessary to control Mtb infection in vivo and the mechanistic basis for this control remains unknown. We dissected the contribution of IRGM1 to immune control of Mtb pathogenesis in vivo and found that Irgm1 deletion leads …


Increased Periventricular Thalamic Damage Gradient In Multiple Sclerosis Detected By Quantitative Gradient Echo Mri, Amjad Samara, Biao Xiang, Bradley Judge, John R Ciotti, Dmitriy A Yablonskiy, Anne H Cross, Matthew R Brier Oct 2024

Increased Periventricular Thalamic Damage Gradient In Multiple Sclerosis Detected By Quantitative Gradient Echo Mri, Amjad Samara, Biao Xiang, Bradley Judge, John R Ciotti, Dmitriy A Yablonskiy, Anne H Cross, Matthew R Brier

2020-Current year OA Pubs

OBJECTIVE: Thalamic tissue damage in multiple sclerosis (MS) follows a 'surface-in' gradient from the ventricular surface. The clinical consequences of this gradient are not completely understood. Using quantitative gradient-recalled echo (qGRE) MRI, we evaluated a periventricular thalamic gradient of tissue integrity in MS and its relationship with clinical variables.

METHODS: Structural and qGRE MRI scans were acquired for a cohort of MS patients and healthy controls (HC). qGRE-derived R2t* values were used as a measure of tissue integrity. Thalamic segmentations were divided into 1-mm concentric bands radiating from the ventricular surface, excluding the CSF-adjacent band. Median R2t* values within these …


Liquid Biopsy In Triple-Negative Breast Cancer: Unlocking The Potential Of Precision Oncology, R Mazzeo, J Sears, L Palmero, S Bolzonello, A A Davis, L Gerratana, F Puglisi Oct 2024

Liquid Biopsy In Triple-Negative Breast Cancer: Unlocking The Potential Of Precision Oncology, R Mazzeo, J Sears, L Palmero, S Bolzonello, A A Davis, L Gerratana, F Puglisi

2020-Current year OA Pubs

In the era of precision oncology, the management of triple-negative breast cancer (TNBC) is rapidly changing and becoming more complicated with a variety of chemotherapy, immunotherapy, and targeted treatment options. Currently, TNBC treatment is based on prognostic and predictive factors including immunohistochemical biomarkers [e.g. programmed death-ligand 1 (PD-L1)] and germline BRCA mutations. Given the current limitation of existing biomarkers, liquid biopsies may serve as clinically useful tools to determine treatment efficacy and response in both the (neo)adjuvant and metastatic settings, for detecting early relapse, and for monitoring clonal evolution during treatment. In this review, we comprehensively summarize current and future …