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Full-Text Articles in Medicine and Health Sciences

Regional Differences In Three-Dimensional Fiber Organization, Smooth Muscle Cell Phenotype, And Contractility In The Pregnant Mouse Cervix, Christopher J Hansen, Christine M O'Brien, Et Al. Dec 2024

Regional Differences In Three-Dimensional Fiber Organization, Smooth Muscle Cell Phenotype, And Contractility In The Pregnant Mouse Cervix, Christopher J Hansen, Christine M O'Brien, Et Al.

2020-Current year OA Pubs

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts. We also detected a greater proportion of contractile smooth muscle cells (SMCs), but an equal proportion of synthetic SMCs, in the upper versus lower cervix. Furthermore, we revealed that the lower cervix had infrequent spontaneous …


Retrospective Derivation Of A Causal Pathway For Diabetic Ketoacidosis In Adult Patients With Type 2 Diabetes Mellitus, Jeffrey A Kline, Nicholas A Wesner, Amina T Sharif, Richard T Griffey, Phillip D Levy, Robert D Welch, George Grunberger Dec 2024

Retrospective Derivation Of A Causal Pathway For Diabetic Ketoacidosis In Adult Patients With Type 2 Diabetes Mellitus, Jeffrey A Kline, Nicholas A Wesner, Amina T Sharif, Richard T Griffey, Phillip D Levy, Robert D Welch, George Grunberger

2020-Current year OA Pubs

BACKGROUND: Type 2 ketone-prone diabetes mellitus (T2KPDM) is thought to occur in men of African descent, with obesity who experienced prolonged hyperglycemia; the role of medication non-adherence as a contributing cause remains unstudied.

RESEARCH DESIGN AND METHODS: This was a retrospective study of unique adults (>18 years) who sought emergency care one of four hospitals in the greater Detroit area. Patients were identified on the basis of a laboratory order for a ß-hydroxybutyrate concentration. Two research coordinators abstracted 119 data fields. Patients were divided into four phenotypes: (1) no prior DM, (2) type 2 DM without prior ketosis, (3) …


Pediatric Providers' Views On Participating In An Hpv Vaccine Quality Improvement Intervention: A Qualitative Analysis, Edan Leshem, Sara Malone, Andrew Solsrud, Sherry Dodd, Shannon Rook, Sharon Graham, Lauren Ericson, Ruoyun Wang, Katie Plax, Jason Newland Dec 2024

Pediatric Providers' Views On Participating In An Hpv Vaccine Quality Improvement Intervention: A Qualitative Analysis, Edan Leshem, Sara Malone, Andrew Solsrud, Sherry Dodd, Shannon Rook, Sharon Graham, Lauren Ericson, Ruoyun Wang, Katie Plax, Jason Newland

2020-Current year OA Pubs

BACKGROUND: Human papillomavirus (HPV), a common sexually transmitted infection in the US, contributes to oropharyngeal and urogenital cancers. To improve HPV vaccine uptake, quality improvement (QI) interventions that address barriers to vaccination in primary care may help. This study aims to understand pediatric primary care providers' (PCP) perspectives on participating in an HPV QI intervention that utilized practice facilitation to improve HPV vaccine uptake in pediatric primary care clinics.

METHODS: Participants were pediatric PCPs whose clinics completed a QI intervention that utilized practice facilitation led by an outside facilitator. One PCP from each practice completed a 15-min semi-structured exit interview. …


Multimodal Oculomotor Assessment Reveals Prodromal Markers Of Parkinson's Disease In Non-Manifesting Lrrk2 G2019s Mutation Carriers, Heidi C Riek, Naomi P Visanji, Isabell C Pitigoi, Daniel G Di Luca, Laura Armengou-Garcia, Nazish Ahmed, Julia E Perkins, Donald C Brien, Jeff Huang, Brian C Coe, Jana Huang, Taneera Ghate, Anthony E Lang, Connie Marras, Douglas P Munoz Dec 2024

Multimodal Oculomotor Assessment Reveals Prodromal Markers Of Parkinson's Disease In Non-Manifesting Lrrk2 G2019s Mutation Carriers, Heidi C Riek, Naomi P Visanji, Isabell C Pitigoi, Daniel G Di Luca, Laura Armengou-Garcia, Nazish Ahmed, Julia E Perkins, Donald C Brien, Jeff Huang, Brian C Coe, Jana Huang, Taneera Ghate, Anthony E Lang, Connie Marras, Douglas P Munoz

2020-Current year OA Pubs

Oculomotor behaviour changes in patients with Parkinson's disease (PD) are a promising source of prodromal disease markers. Capitalizing on this phenomenon to facilitate early diagnosis requires oculomotor assessment in prodromal cohorts. We examined oculomotor behaviour in non-manifesting LRRK2 G2019S mutation carriers (LRRK2-NM), who have heightened PD risk.Seventeen LRRK2-NM participants, 47 patients with idiopathic PD, and 63 healthy age-matched control participants completed an interleaved pro- and antisaccade task while undergoing video-based eye-tracking. We analyzed between-group differences in saccade, pupil, blink, and fixation acquisition behaviour. Patients with PD showed previously demonstrated abnormalities (saccade hypometria, antisaccade errors). Relative to controls, LRRK2-NM participants and …


Brain Volumes, Cognitive, And Adaptive Skills In School-Age Children With Down Syndrome, Rebecca Grzadzinski, Kelly Botteron, Natasha Marrus, Robert Mckinstry, Et Al. Dec 2024

Brain Volumes, Cognitive, And Adaptive Skills In School-Age Children With Down Syndrome, Rebecca Grzadzinski, Kelly Botteron, Natasha Marrus, Robert Mckinstry, Et Al.

2020-Current year OA Pubs

BACKGROUND: Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS.

METHODS: School-age children (mean = 9.7 years ± 1.1) underwent comprehensive assessments, including cognitive and adaptive assessments, as well as an MRI scan without the use of sedation. Children with DS (n = 35) were compared to available samples of typically developing (TD; n …


The Effect Of A Low-Carbohydrate Diet On Evoked Pain And Quality Of Life In Non-Hispanic Black Women With Knee Osteoarthritis: A Pilot Study, Asia M Wiggins, Larissa J Strath, Gray E Mcpherson, Barbara A Gower, Amy M Goss, Burel R Goodin, Robert E Sorge Dec 2024

The Effect Of A Low-Carbohydrate Diet On Evoked Pain And Quality Of Life In Non-Hispanic Black Women With Knee Osteoarthritis: A Pilot Study, Asia M Wiggins, Larissa J Strath, Gray E Mcpherson, Barbara A Gower, Amy M Goss, Burel R Goodin, Robert E Sorge

2020-Current year OA Pubs

BACKGROUND: Knee osteoarthritis (KOA) is a prevalent chronic pain condition that can significantly impact quality of life and contribute to recognized chronic pain racial disparities. We have shown that a low-carbohydrate diet (LCD) can reduce KOA-related pain. Our previous work suggested that the LCD was more beneficial for women and non-Hispanic Black (NHB) adults, but our sample was not sufficiently diverse. Thus, we sought to determine whether the LCD may be beneficial for NHB women with KOA on measures of self-reported and evoked pain.

METHODS: Fourteen NHB women (M = 55.93, S.D. = 7.79 years of age) with KOA were …


M1 Recruitment During Interleaved Practice Is Important For Encoding, Not Just Consolidation, Of Skill Memory, Taewon Kim, Hakjoo Kim, Benjamin A Philip, David L Wright Dec 2024

M1 Recruitment During Interleaved Practice Is Important For Encoding, Not Just Consolidation, Of Skill Memory, Taewon Kim, Hakjoo Kim, Benjamin A Philip, David L Wright

2020-Current year OA Pubs

The primary motor cortex (M1) is crucial for motor skill learning. We examined its role in interleaved practice, which enhances retention (vs. repetitive practice) through M1-dependent consolidation. We hypothesized that cathodal transcranial direct current stimulation (ctDCS) to M1 would disrupt retention. We found that ctDCS reduced retention due to weakened encoding during acquisition, not disrupted consolidation. These results highlight M1's broad role in encoding and retention of novel motor skills.


Number Of Prescription Medications And Overall Survival In Metastatic Castrate-Resistant Prostate Cancer, Carley R Pickett, Daniel B Eaton, Krishny Karunanandaa, Emily Cybulla, Brendan T Heiden, Su-Hsin Chang, Yan Yan, Melanie P Subramanian, Varun Puri, Martin W Schoen Dec 2024

Number Of Prescription Medications And Overall Survival In Metastatic Castrate-Resistant Prostate Cancer, Carley R Pickett, Daniel B Eaton, Krishny Karunanandaa, Emily Cybulla, Brendan T Heiden, Su-Hsin Chang, Yan Yan, Melanie P Subramanian, Varun Puri, Martin W Schoen

2020-Current year OA Pubs

No abstract provided.


The Improving Treatment Decisions For Patients With Aortic Stenosis Through Shared Decision Making (Impact Sdm) Study: Study Protocol For A Cluster Randomized Stepped Wedge Trial, Karen Sepucha, Nishath Quader, Alexander A Brescia, Et Al. Dec 2024

The Improving Treatment Decisions For Patients With Aortic Stenosis Through Shared Decision Making (Impact Sdm) Study: Study Protocol For A Cluster Randomized Stepped Wedge Trial, Karen Sepucha, Nishath Quader, Alexander A Brescia, Et Al.

2020-Current year OA Pubs

BACKGROUND: The American College of Cardiology, American Heart Association, and Centers for Medicare and Medicaid Services recommend shared decision-making (SDM) for patients with severe aortic stenosis choosing between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). Although tools such as patient decision aids (DAs) and training in SDM have been shown to improve SDM, implementation of SDM and DAs is limited. The IMproving treatment decisions for Patients with AortiC stenosis Through Shared Decision Making (IMPACT SDM) study aims to (1) determine the effectiveness of the interventions (a DA and clinician SDM training) in achieving SDM (primary outcome) …


Primary Anorectal Mammary-Like Adenocarcinoma: A Potential Diagnostic Pitfall With Conventional Colorectal Adenocarcinoma, Margaret L Axelrod, Xiuli Liu, Pooja Navale Dec 2024

Primary Anorectal Mammary-Like Adenocarcinoma: A Potential Diagnostic Pitfall With Conventional Colorectal Adenocarcinoma, Margaret L Axelrod, Xiuli Liu, Pooja Navale

2020-Current year OA Pubs

Anogenital mammary-like glands (AGMLGs) are present in the anogenital region that bear striking morphologic and protein-expression similarities to mammary glands in the breast. AGMLGs can give rise to both benign and malignant lesions which mimic primary breast lesions. Herein, we report two mammary-type adenocarcinomas arising from AGMLGs, including one in the previously unreported site of the rectum. Recognition of mammary-type adenocarcinoma in the rectal and anogenital regions is crucial as clinical management options may differ compared to conventional colorectal adenocarcinomas.


The Biomechanics Of Fibrillin Microfibrils: Lessons From The Ciliary Zonule, Pooja Rathaur, Juan Rodriguez, John Kuchtey, Samuel Insignares, Wendell B Jones, Rachel W Kuchtey, Steven Bassnett Dec 2024

The Biomechanics Of Fibrillin Microfibrils: Lessons From The Ciliary Zonule, Pooja Rathaur, Juan Rodriguez, John Kuchtey, Samuel Insignares, Wendell B Jones, Rachel W Kuchtey, Steven Bassnett

2020-Current year OA Pubs

Marfan syndrome is an inherited connective tissue disorder that affects the cardiovascular, musculoskeletal, and ocular systems. It is caused by pathogenic variants in the fibrillin-1 gene (


Comparative Analysis Of Outcomes In Adult Spinal Deformity Patients With Proximal Junctional Kyphosis Or Failure Initially Fused To Upper Versus Lower Thoracic Spine, Oluwatobi O Onafowokan, Munish Chandra Gupta, Et Al. Dec 2024

Comparative Analysis Of Outcomes In Adult Spinal Deformity Patients With Proximal Junctional Kyphosis Or Failure Initially Fused To Upper Versus Lower Thoracic Spine, Oluwatobi O Onafowokan, Munish Chandra Gupta, Et Al.

2020-Current year OA Pubs

No abstract provided.


Structural Variant Allelic Heterogeneity In Mecp2 Duplication Syndrome Provides Insight Into Clinical Severity And Variability Of Disease Expression, Davut Pehlivan, Marwan S Shinawi, Et Al. Dec 2024

Structural Variant Allelic Heterogeneity In Mecp2 Duplication Syndrome Provides Insight Into Clinical Severity And Variability Of Disease Expression, Davut Pehlivan, Marwan S Shinawi, Et Al.

2020-Current year OA Pubs

BACKGROUND: MECP2 Duplication Syndrome, also known as X-linked intellectual developmental disorder Lubs type (MRXSL; MIM: 300260), is a neurodevelopmental disorder caused by copy number gains spanning MECP2. Despite varying genomic rearrangement structures, including duplications and triplications, and a wide range of duplication sizes, no clear correlation exists between DNA rearrangement and clinical features. We had previously demonstrated that up to 38% of MRXSL families are characterized by complex genomic rearrangements (CGRs) of intermediate complexity (2 ≤ copy number variant breakpoints <  5), yet the impact of these genomic structures on regulation of gene expression and phenotypic manifestations have not been investigated.

METHODS: To study the role of the genomic rearrangement structures on an individual's clinical phenotypic variability, we employed a comprehensive …


Momordicine-I Suppresses Head And Neck Cancer Growth By Modulating Key Metabolic Pathways, Debojyoty Bandyopadhyay, Ellen T Tran, Ruchi A Patel, Matthew A Luetzen, Kevin Cho, Leah P Shriver, Gary J Patti, Mark A Varvares, David A Ford, Kyle S Mccommis, Ratna B Ray Dec 2024

Momordicine-I Suppresses Head And Neck Cancer Growth By Modulating Key Metabolic Pathways, Debojyoty Bandyopadhyay, Ellen T Tran, Ruchi A Patel, Matthew A Luetzen, Kevin Cho, Leah P Shriver, Gary J Patti, Mark A Varvares, David A Ford, Kyle S Mccommis, Ratna B Ray

2020-Current year OA Pubs

One of the hallmarks of cancer is metabolic reprogramming which controls cellular homeostasis and therapy resistance. Here, we investigated the effect of momordicine-I (M-I), a key bioactive compound from Momordica charantia (bitter melon), on metabolic pathways in human head and neck cancer (HNC) cells and a mouse HNC tumorigenicity model. We found that M-I treatment on HNC cells significantly reduced the expression of key glycolytic molecules, SLC2A1 (GLUT-1), HK1, PFKP, PDK3, PKM, and LDHA at the mRNA and protein levels. We further observed reduced lactate accumulation, suggesting glycolysis was perturbed in M-I treated HNC cells. Metabolomic analyses confirmed a marked …


Microglial Cd2ap Deficiency Exerts Protection In An Alzheimer's Disease Model Of Amyloidosis, Lingliang Zhang, David M. Holtzman, Et Al. Dec 2024

Microglial Cd2ap Deficiency Exerts Protection In An Alzheimer's Disease Model Of Amyloidosis, Lingliang Zhang, David M. Holtzman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The CD2-associated protein (CD2AP) was initially identified in peripheral immune cells and regulates cytoskeleton and protein trafficking. Single nucleotide polymorphisms (SNPs) in the CD2AP gene have been associated with Alzheimer's disease (AD). However, the functional role of CD2AP, especially its role in microglia during AD onset, remains elusive.

METHODS: CD2AP protein levels in cultured primary cells and in 5xFAD mice was studied. Microglial CD2AP-deficient mice were crossed with 5xFAD mice and the offspring were subjected to neuropathological assessment, behavioral tests, electrophysiology, RNA-seq, Golgi staining, and biochemistry analysis. Primary microglia were also isolated for assessing their uptake and morphology changes. …


Addressing Lung Truncation In 99mtc-Maa Spect/Ct For 90y Microsphere Radioembolization Treatment Planning, M Allan Thomas, Richard Laforest, John Karageorgiou, Dan Giardina, Tyler J Fraum, Chris D Malone, Justin K Mikell Dec 2024

Addressing Lung Truncation In 99mtc-Maa Spect/Ct For 90y Microsphere Radioembolization Treatment Planning, M Allan Thomas, Richard Laforest, John Karageorgiou, Dan Giardina, Tyler J Fraum, Chris D Malone, Justin K Mikell

2020-Current year OA Pubs

BACKGROUND: Prior studies have established that macroaggregated albumin (MAA)-SPECT/CT offers more robust lung shunt fraction (LSF) and lung mean absorbed dose (LMD) estimates in

METHODS: Lung truncation was simulated in 56 cases with adequate (> 90%, mean: 98%) lung coverage in MAA-SPECT/CT by removing slices in ~ 5 mm increments from the lung apices to the diaphragm. A wide range of lung coverages from 100% to <  1% in ~ 2% increments were created. LSF and LMD were calculated with four methods. (1) 2D planar imaging standard (not truncated), truncated lung SPECT/CT data was: (2) used with no corrections (SPECT

RESULTS: Averaged across simulated lung coverages from 40 to 80%, percent errors relative to non-truncated data for SPECT

CONCLUSION: LSF and LMD can be estimated for


Conventional Cytogenetic Analysis Of Solid Tumor Abnormalities: A 25-Year Review Of Proficiency Test Results From The College Of American Pathologists/American College Of Medical Genetics And Genomics Cytogenetics Committee, Rachel K Vanderscheldon, Yang Cao, Et Al. Dec 2024

Conventional Cytogenetic Analysis Of Solid Tumor Abnormalities: A 25-Year Review Of Proficiency Test Results From The College Of American Pathologists/American College Of Medical Genetics And Genomics Cytogenetics Committee, Rachel K Vanderscheldon, Yang Cao, Et Al.

2020-Current year OA Pubs

No abstract provided.


Understanding Rare Genetic Variants Within The Terminal Pathway Of Complement System In Preeclampsia, A Inkeri Lokki, Michael Triebwasser, Emma Daly, Finnpec Core Investigator Group, Mitja I Kurki, Markus Perola, Kirsi Auro, Jane E Salmon, Java Anuja, Mark Daly, John P Atkinson, Hannele Laivuori, Seppo Meri Dec 2024

Understanding Rare Genetic Variants Within The Terminal Pathway Of Complement System In Preeclampsia, A Inkeri Lokki, Michael Triebwasser, Emma Daly, Finnpec Core Investigator Group, Mitja I Kurki, Markus Perola, Kirsi Auro, Jane E Salmon, Java Anuja, Mark Daly, John P Atkinson, Hannele Laivuori, Seppo Meri

2020-Current year OA Pubs

Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation of complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study of 609 women with preeclampsia and 2092 non-preeclamptic controls, we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense variants in the C5 gene that predispose to preeclampsia (rs200674959: I1296V, OR (CI95) = 24.13 (1.25-467.43), p value = 0.01 and rs147430470: I330T, OR (CI95) = 22.75 (1.17-440.78), p value = 0.01). In addition, one predisposing rare variant …


The Pace Of Biological Aging Partially Explains The Relationship Between Socioeconomic Status And Chronic Low Back Pain Outcomes, Edwin N Aroke, Jai Ganesh Nagidi, Vinodh Srinivasasainagendra, Tammie L Quinn, Fiona B A T Agbor, Kiari R Kinnie, Hemant K Tiwari, Burel R Goodin Dec 2024

The Pace Of Biological Aging Partially Explains The Relationship Between Socioeconomic Status And Chronic Low Back Pain Outcomes, Edwin N Aroke, Jai Ganesh Nagidi, Vinodh Srinivasasainagendra, Tammie L Quinn, Fiona B A T Agbor, Kiari R Kinnie, Hemant K Tiwari, Burel R Goodin

2020-Current year OA Pubs

INTRODUCTION: Having a lower socioeconomic status (SES) is a predictor of age-related chronic conditions, including chronic low back pain (cLBP). We aimed to examine whether the pace of biological aging mediates the relationship between SES and cLBP outcomes - pain intensity, pain interference, and physical performance.

METHODS: We used the Dunedin Pace of Aging Calculated from the Epigenome (DunedinPACE) software to determine the pace of biological aging in adults ages 18 to 85 years with no cLBP (n = 74), low-impact pain (n = 56), and high-impact pain (n = 77).

RESULTS: The mean chronological age of the participants was …


Experimental Pain Sensitivity And Parental Pain Catastrophizing, Gourav Banerjee, Joel Brown, Alana Mcmichael, Arbi Ben Abdallah, Sarah Buday, Deanna M Barch, Thomas Baranski, Simon Haroutounian, Jacob Aubuchon, Hadas Nahman-Averbuch Dec 2024

Experimental Pain Sensitivity And Parental Pain Catastrophizing, Gourav Banerjee, Joel Brown, Alana Mcmichael, Arbi Ben Abdallah, Sarah Buday, Deanna M Barch, Thomas Baranski, Simon Haroutounian, Jacob Aubuchon, Hadas Nahman-Averbuch

2020-Current year OA Pubs

BACKGROUND/OBJECTIVES: Variability in biopsychosocial factors can explain the interindividual variability in pain. One factor that can impact pain is the pain catastrophizing level. Interestingly, parental pain catastrophizing is related to the severity of the clinical pain of their children. This study explored whether parental pain catastrophizing is also associated with their children's experimental pain sensitivity.

METHODS: Forty-five healthy girls (mean age 12.07 ± 1.47 years) and one of their parents participated in this study. Parents completed the Pain Catastrophizing Scale (PCS) about their child's pain (PCS-Parent

RESULTS: No significant relationships were found between the experimental pain sensitivity measures and either …


Clover (Clostridium Difficile Vaccine Efficacy Trial) Study: A Phase 3, Randomized Trial Investigating The Efficacy And Safety Of A Detoxified Toxin A/B Vaccine In Adults 50 Years And Older At Increased Risk Of Clostridioides Difficile Infection, Curtis J Donskey, Erik R Dubberke, Et Al. Dec 2024

Clover (Clostridium Difficile Vaccine Efficacy Trial) Study: A Phase 3, Randomized Trial Investigating The Efficacy And Safety Of A Detoxified Toxin A/B Vaccine In Adults 50 Years And Older At Increased Risk Of Clostridioides Difficile Infection, Curtis J Donskey, Erik R Dubberke, Et Al.

2020-Current year OA Pubs

BACKGROUND: Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.

METHODS: This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were …


The C-Terminal Activating Domain Promotes Pannexin 1 Channel Opening, Erik Henze, Jacqueline J Ehrlich, Janice L Robertson, Eric Gelsleichter, Toshimitsu Kawate Dec 2024

The C-Terminal Activating Domain Promotes Pannexin 1 Channel Opening, Erik Henze, Jacqueline J Ehrlich, Janice L Robertson, Eric Gelsleichter, Toshimitsu Kawate

2020-Current year OA Pubs

Pannexin 1 (Panx1) constitutes a large pore channel responsible for the release of adenosine triphosphate (ATP) from apoptotic cells. Strong evidence indicates that caspase-mediated cleavage of the C-terminus promotes the opening of the Panx1 channel by unplugging the pore. However, this simple pore-plugging mechanism alone cannot account for the observation that a Panx1 construct ending before the caspase cleavage site remains closed. Here, we show that a helical region located immediately before the caspase cleavage site, referred to as the "C-terminal activating domain (CAD)", plays a pivotal role in facilitating Panx1 activation. Electrophysiology and mutagenesis studies uncovered that two conserved …


Changes In Reproductive Health Information-Seeking Behaviors After The Dobbs Decision: Systematic Search Of The Wikimedia Database, Mackenzie Lemieux, Cyrus Zhou, Caroline Cary, Jeannie Kelly Dec 2024

Changes In Reproductive Health Information-Seeking Behaviors After The Dobbs Decision: Systematic Search Of The Wikimedia Database, Mackenzie Lemieux, Cyrus Zhou, Caroline Cary, Jeannie Kelly

2020-Current year OA Pubs

BACKGROUND: After the US Supreme Court overturned Roe v. Wade, confusion followed regarding the legality of abortion in different states across the country. Recent studies found increased Google searches for abortion-related terms in restricted states after the Dobbsv. Jackson Women's Health Organization decision was leaked. As patients and providers use Wikipedia (Wikimedia Foundation) as a predominant medical information source, we hypothesized that changes in reproductive health information-seeking behavior could be better understood by examining Wikipedia article traffic.

OBJECTIVE: This study aimed to examine trends in Wikipedia usage for abortion and contraception information before and after the Dobbs decision.

METHODS: Page …


First-In-Human Dose-Escalation Study Of Fianlimab, An Antilymphocyte Activation Gene-3 Antibody, With Cemiplimab In Patients With Advanced Malignancies, Nehal J Lakhani, Haeseong Park, Et Al. Dec 2024

First-In-Human Dose-Escalation Study Of Fianlimab, An Antilymphocyte Activation Gene-3 Antibody, With Cemiplimab In Patients With Advanced Malignancies, Nehal J Lakhani, Haeseong Park, Et Al.

2020-Current year OA Pubs

PURPOSE: Preclinical data indicate that fianlimab (antilymphocyte activation gene-3) plus cemiplimab (anti-PD-1) enhances antitumor activity. Here, we report prespecified final analyses of the dose-escalation part of a first-in-human, phase 1 study (NCT03005782) of fianlimab as monotherapy and in combination with cemiplimab in patients with advanced malignancies.

PATIENTS AND METHODS: Adult patients received 1 to 40 mg/kg of fianlimab plus 350 mg of cemiplimab every 3 weeks (Q3W) across various dose-escalation schedules. Primary objectives were the rate of dose-limiting toxicities, adverse events (including immune mediated), deaths, laboratory abnormalities, and pharmacokinetics. Secondary outcomes were objective response rate, best overall response, duration of …


Conceptualization, Measurement, And Contributors To Participation Among People Living With Parkinson’S Disease, Moon Young Kim Dec 2024

Conceptualization, Measurement, And Contributors To Participation Among People Living With Parkinson’S Disease, Moon Young Kim

WUSM Theses and Dissertations – All Programs

Participation is a key outcome of rehabilitation and key to successful aging. Individuals with Parkinson’s disease (PD) often experience significant challenges in maintaining participation in meaningful activities and roles. This dissertation examines the influence of living with PD on participation by integrating findings from three studies: a systematic review, a cross-sectional study, and a longitudinal study.

The systematic review synthesized the existing quantitative research on participation in people with PD, revealing inconsistencies in the conceptualization of participation. While the evaluation tools aimed at assessing participation in PD showed acceptable coverage of domains of participation, the assessment of the aspects of …


Impact Of Site-Specific Conjugation Strategies On The Pharmacokinetics Of Antibody Conjugated Radiotherapeutics, Ábel Nagy, David Ulmert, Wahed Zedan, Claire M Storey, Julie Park, Susanne Geres, Katharina Lückerath, Kjell Sjöström, Hadis Westin, Norbert Peekhaus, Daniel Lj Thorek, Amelie Eriksson Karlström, Mohamed Altai Dec 2024

Impact Of Site-Specific Conjugation Strategies On The Pharmacokinetics Of Antibody Conjugated Radiotherapeutics, Ábel Nagy, David Ulmert, Wahed Zedan, Claire M Storey, Julie Park, Susanne Geres, Katharina Lückerath, Kjell Sjöström, Hadis Westin, Norbert Peekhaus, Daniel Lj Thorek, Amelie Eriksson Karlström, Mohamed Altai

2020-Current year OA Pubs

Antibody radionuclide conjugates are an emerging modality for targeted imaging and potent therapy of disseminated disease. Coupling of radionuclides to monoclonal antibodies (mAbs) is typically achieved by applying non-site-specific labelling techniques. With the ambition of reducing variability, increasing labelling efficacy and stability, several site-specific conjugation strategies have been developed in recent years for toxin- and fluorophore-mAb conjugates. In this study, we studied two site-specific labelling strategies for the conjugation of the macrocyclic chelating agent, DOTA, to the anti-Leucine Rich Repeat Containing 15 (LRRC15) mAb DUNP19. Specifically, one approach utilized a DOTA-bearing peptide (FcIII) with a strong affinity for the fragment …


A Practical Clinical Approach To Navigate Pulmonary Embolism Management: A Primer And Narrative Review Of The Evolving Landscape, Kevin Benavente, Bradley Fujiuchi, Hafeez Ul Hassan Virk, Pavan K Kavali, Walter Ageno, Geoffrey D Barnes, Marc Righini, Mahboob Alam, Rachel P Rosovsky, Chayakrit Krittanawong Dec 2024

A Practical Clinical Approach To Navigate Pulmonary Embolism Management: A Primer And Narrative Review Of The Evolving Landscape, Kevin Benavente, Bradley Fujiuchi, Hafeez Ul Hassan Virk, Pavan K Kavali, Walter Ageno, Geoffrey D Barnes, Marc Righini, Mahboob Alam, Rachel P Rosovsky, Chayakrit Krittanawong

2020-Current year OA Pubs

Advances in imaging, pharmacological, and procedural technologies have rapidly expanded the care of pulmonary embolism. Earlier, more accurate identification and quantification has enhanced risk stratification across the spectrum of the disease process, with a number of clinical tools available to prognosticate outcomes and guide treatment. Direct oral anticoagulants have enabled a consistent and more convenient long-term therapeutic option, with a greater shift toward outpatient treatment for a select group of low-risk patients. The array of catheter-directed therapies now available has contributed to a more versatile and nuanced armamentarium of treatment options, including ultrasound-facilitated thrombolysis and mechanical thrombectomy. Research into supportive …


Transcriptomic Landscape Of Mammalian Ventral Pallidum At Single-Cell Resolution, Lite Yang, Lisa Z Fang, Michelle R Lynch, Chang S Xu, Hannah J Hahm, Yufen Zhang, Monique R Heitmeier, Vincent D Costa, Vijay K Samineni, Meaghan C Creed Dec 2024

Transcriptomic Landscape Of Mammalian Ventral Pallidum At Single-Cell Resolution, Lite Yang, Lisa Z Fang, Michelle R Lynch, Chang S Xu, Hannah J Hahm, Yufen Zhang, Monique R Heitmeier, Vincent D Costa, Vijay K Samineni, Meaghan C Creed

2020-Current year OA Pubs

The ventral pallidum (VP) is critical for motivated behaviors. While contemporary work has begun to elucidate the functional diversity of VP neurons, the molecular heterogeneity underlying this functional diversity remains incompletely understood. We used single-nucleus RNA sequencing and in situ hybridization to define the transcriptional taxonomy of VP cell types in mice, macaques, and baboons. We found transcriptional conservation between all three species, within the broader neurochemical cell types. Unique dopaminoceptive and cholinergic subclusters were identified and conserved across both primate species but had no homolog in mice. This harmonized consensus VP cellular atlas will pave the way for understanding …


A Potent Pan-Sarbecovirus Neutralizing Antibody Resilient To Epitope Diversification, Laura E Rosen, Zhuoming Liu, Sean P J Whelan, Et Al. Dec 2024

A Potent Pan-Sarbecovirus Neutralizing Antibody Resilient To Epitope Diversification, Laura E Rosen, Zhuoming Liu, Sean P J Whelan, Et Al.

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, …


Genomic Surveillance Of Sars-Cov-2 In Nepal, Binod Khadka, Kathie A Mihindukulasuriya, Lindsay Droit, Anne M Paredes, Scott A Handley, David Wang, Et Al. Dec 2024

Genomic Surveillance Of Sars-Cov-2 In Nepal, Binod Khadka, Kathie A Mihindukulasuriya, Lindsay Droit, Anne M Paredes, Scott A Handley, David Wang, Et Al.

2020-Current year OA Pubs

During the COVID-19 pandemic, Nepal, like other countries, faced emerging SARS-CoV-2 variants. To evaluate the circulating variants, 278 samples collected between September 2021 and March 2022 were sequenced in the country. From these, 229 high-quality genomes were obtained (82.97% Omicron and 17.03% Delta) highlighting the genomic diversity of SARS-CoV-2 in Nepal.