Digital Commons Network^™

Administration Of Anti-Gfap Antibodies Increases Cgrp Expression And Increases Pain Hypersensitivity In Spinal Cord Injured Animals

Faculty, Staff and Student Publications

Background: Spinal cord injury (SCI) results in a multitude of cellular and pathological changes including neuronal loss, axonal damage, gliosis, and loss of motor and sensory function. In 40%-70% of patients, SCI can also trigger the development of neuropathic pain. Our previous study demonstrated that SCI patients who developed autoantibodies to glial fibrillary acidic protein (GFAP) were at increased risk for the subsequent development of neuropathic pain. However, whether GFAP autoantibodies (GFAPab) contribute to the development of neuropathic pain after SCI had yet to be examined.

Objective: Using a mid-thoracic contusion model of SCI in male Sprague-Dawley rats, we examined …

Daily Movement Activities Are Associated With Within-Person Instability Of Cognitive Function In Older Adults: Evidence From An Ambulatory Assessment Study, Donna Coffman

Faculty, Staff and Student Publications

Background and objectives: Physical inactivity and excessive sedentary time (ST) are associated with poor cognitive health in older adults. However, current literature largely relies on cross-sectional designs or in-lab cognitive assessments, which do not adequately reflect cognitive function in naturalistic settings. Further, existing studies have largely overlooked the variability or the instability in daily cognitive function, which represents a critical marker of cognitive decline. This ambulatory assessment study examined the temporal associations of daily movement behaviors with the mean levels and the variability of cognition among older adults at risk of dementia.

Research design and methods: 96 older adults from …

Oral Microbiome Brain Axis And Cognitive Performance In Older Adults, Vivian Ramirez, Lisa L Barnes, Ali Keshavarzian, Klodian Dhana, Robin M Voigt

Faculty, Staff and Student Publications

The human oral microbiota is a community of microorganisms that reside in the oral cavity, including lingual, buccal, and saliva, each niche with a distinct microbial composition. Alterations in oral microbiota have been associated with an increased risk of Alzheimer’s disease (AD). This study used data from 143 older adults in the MIND trial to evaluate the association between oral microbiome and cognitive function. Oral niche-specific differences (saliva, buccal, and lingual), as well as the microbiome composition differences (α and β diversity), were associated with cognitive function. A lower abundance of Gemella and a higher abundance of anaerobic pro-inflammatory bacteria …

Editorial: Women In Brain Imaging And Stimulation, Volume Ii: 2024, Molly S Hermiller, Ruogu Fang, Wen Li

Faculty, Staff and Student Publications

No abstract provided.

Targeting Ferroptosis For Neuroprotection: Potential Therapeutic Avenues In Neurodegenerative And Neuropsychiatric Diseases, Muhammad S Khan, Qichan Hu, Kendrix Okeibunor, Liang Ma, Jean C Bopassa

Faculty, Staff and Student Publications

Ferroptosis is an iron-dependent programmed cell death that plays an important role in neurodegenerative and neuropsychiatric diseases. In the present study, we have highlighted how different risk factors are involved in the induction of ferroptosis in brain cells. In addition, we also demonstrated how ferroptosis plays an important role in different brain diseases. In our study why we focused and elaborated on the mechanisms of ferroptosis only in brain cells (Neurons, oligodendrocytes, and microglia) because they are particularly vulnerable to such kind of cell death. Additionally, brain cells are more dependent on mitochondrial function, iron regulation, and high levels of …

Therapeutic Alliance In A Culturally Tailored Transition Program For Latino Young Adults With Autism And Their Families, Antonio F Pagán, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

Latino young adults with autism spectrum disorder (ASD) often face barriers to accessing culturally appropriate interventions that support adaptive functioning and family dynamics. Therapeutic alliance, the collaborative and trusting relationship between participants and providers, is a critical component of intervention success, yet its role in culturally tailored programs for Latino families remains underexplored. The present study examined therapeutic alliance in ¡Iniciando! la Adultez, a 12-week, culturally adapted intervention for Latino young adults with ASD and their Spanish-speaking parents. The program integrates Latino cultural values and language and consists of parent group therapy, young adult group therapy, and individual therapy sessions. …

Heritability And Shared Environmental Effects Of Brain Diseases In 12,040 Extended Families, Janna I R Dijkstra, Marc Hulsman, Lisa Waterink, Henne Holstege, Charlotte E Teunissen, Wouter F L Christiaansen, Bryan A De Jong, Peter Kochunov, Brian Donohue, Marissa D Zwan, Anouk Den Braber, Lisa Vermunt, Sven J Van Der Lee

Faculty, Staff and Student Publications

Brain diseases have complex patterns of genetic and environmental risk factors, and better understanding of these risks is required for more effective prevention strategies. Participants of the Dutch Brain Research Registry provided detailed information on family structure and occurrence of brain diseases. A total of 12,040 participants (73% female, aged 64.9 ± 11 years) provided information on 101,379 family members (53% female, aged 62 ± 25 years). We estimated heritability (h2) of the nine most common brain diseases using polygenic modeling in SOLAR and assessed variations in h2 through bootstrapping; Alzheimer’s disease (AD) (h2 = …

A Prior-Knowledge-Guided Feature Selection Method And Its Application To Biomarker Identification Of Schizophrenia, Ying Xing, Godfrey D Pearlson, Peter Kochunov, Vince D Calhoun, Yuhui Du

Faculty, Staff and Student Publications

Despite considerable efforts to uncover the neural basis of psychiatric disorders using neuroimaging, few methods utilize intrinsic brain-derived knowledge, leading to limited specificity and discriminability in biomarker identification. To leverage the inherent characteristics within the brain, we propose a prior-knowledge-guided feature selection method to flexibly unveil discriminative and target-oriented biomarkers of psychiatric disorders. Specifically, we construct a constrained sparse regularization allowing for the flexible integration of diverse prior knowledge to identify sparse neuroimaging features linked to specific psychopathology. Additionally, we simultaneously integrate graph-based regularization and redundancy-removal regularization to further ensure the discriminability and independence among the selected features. Different priors …

Brazilian Psychiatric Association Guidelines For The Treatment Of Social Anxiety Disorder, Leonardo Baldaçara, Thales Marcon Almeida, Diogo Cesar Dos Santos, Ana Beatriz Paschoal, Aldo Felipe Pinto, Luiz Antonio Vesco Gaiotto, Diogo De Lacerda Veiga, Fabiano Franca Loureiro, Leandro Fernandes Malloy-Diniz, Roseli Lage De Oliveira, Quirino Cordeiro, Marsal Sanches, Antônio E Nardi, Antônio Geraldo Da Silva, Ricardo R Uchida

Faculty, Staff and Student Publications

Social anxiety disorder (SAD), one of the most prevalent anxiety disorders, is not well recognized. In most cases, SAD follows an unremitted and chronic course, affecting individual functioning in relationships, education, and work. Due to the disorder’s relevance in Brazil, guideline-based treatments adapted to the Brazilian social and economic context are needed. We conducted a systematic review assessing several treatment modalities for SAD. PubMed, Cochrane, SciELO, and ClinicalTrials.gov were searched using the Medical Subject Headings social anxiety disorder and social phobia. Of the 438 selected articles, 20 were selected. Selective serotonin reuptake inhibitors are considered a first-line treatment for SAD …

Trends In Contacts Made By Immigrants To The National Domestic Violence Hotline, Before And During The Covid-19 Pandemic, Sarah Treves-Kagan, Vi D Le, Liris S Berra, Colleen M Ray, Yanet Ruvalcaba, Leila Wood, Denise V D'Angelo, Tatiana M Vera, Lianne Fuino Estefan

Faculty, Staff and Student Publications

Objectives: Immigrants in the United States are more likely than nonimmigrants to experience risk factors for intimate partner violence (IPV) and problems in getting support. The COVID-19 pandemic and recent incidents of xenophobia and anti-immigrant sentiment may have exacerbated exposure to IPV risk factors. We examined immigrant experiences of IPV before and during the COVID-19 pandemic.

Methods: This study identified changes in characteristics of abuse, services used, referrals, and barriers to services among those who contacted the National Domestic Violence Hotline (NDVH) and identified as immigrants, reported immigration status as a concern, needed immigration support, and/or identified immigration status as …

The Interplay Between Pulse Width And Activation Depth In Tens: A Computational Study, Abhishek Datta

Faculty, Staff and Student Publications

Background: Transcutaneous electrical nerve stimulation (TENS) has been a commonly used modality to relieve aches and pain for over 40 years. Commercially available devices provide multiple therapy modes involving a different combination of frequency and pulse width with intensity. While frequency sets sensation, intensity helps determine tolerability, longer pulse width is reported to induce a feeling of deeper stimulation. In fact, longer pulse width has been empirically shown to deliver current into deeper tissues, but in context of other electrical stimulation modalities. The goal of this study was to unpack the relationship between pulse width and activation depth in TENS. …

Long-Term Dynamic Profiles Of Cognitive Kinases Induced By Different Learning Protocols, Yili Zhang, Rong-Yu Liu, Paul Smolen, John H Byrne

Faculty, Staff and Student Publications

Learning is associated with activation of multiple protein kinases, but few details are known about the activation dynamics in response to different learning protocols. We addressed this issue by examining the long-term dynamics of kinases critical for long term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse. Three serotonin (5-HT) protocols have been found to induce LTF with distinct effectiveness: the five-pulse regular-spaced Standard protocol; the five-pulse irregular-spaced Enhanced protocol; and the two-pulse protocol with an interval of 45 min. We previously compared long-term dynamics of the mitogen-activated protein kinase (MAPK) isoform ERK after these protocols. Here we examined the …

Quantitatively Assessing The Impact Of The Quality Of Snomed Ct Subtype Hierarchy On Cohort Queries, Xubing Hao, Xiaojin Li, Yan Huang, Jay Shi, Rashmie Abeysinghe, Cui Tao, Kirk Roberts, Guo-Qiang Zhang, Licong Cui

Faculty, Staff and Student Publications

Objective: SNOMED CT provides a standardized terminology for clinical concepts, allowing cohort queries over heterogeneous clinical data including Electronic Health Records (EHRs). While it is intuitive that missing and inaccurate subtype (or is-a) relations in SNOMED CT reduce the recall and precision of cohort queries, the extent of these impacts has not been formally assessed. This study fills this gap by developing quantitative metrics to measure these impacts and performing statistical analysis on their significance.

Material and methods: We used the Optum de-identified COVID-19 Electronic Health Record dataset. We defined micro-averaged and macro-averaged recall and precision metrics to assess the …

Polygenic Scores Contribution To Parkinson’S Disease Comorbidities, Carlos F Hernández, Camilo Villaman, Cristian Tejos, Gabriela M Repetto, Costin Leu, Dennis Lal, Ignacio F Mata, Andrés D Klein, Eduardo Pérez-Palma

Faculty, Staff and Student Publications

Comorbidities are common in Parkinson’s disease and significantly impact the disease progression and management. While polygenic scores have been widely used to assess genetic risk for complex diseases, their role in comorbidity presentation in Parkinson’s disease remains unclear. This study investigates whether genetic predisposition to comorbidities, as measured by polygenic scores, differs between individuals with Parkinson’s disease and the general population and explores how genetic risk influences disease onset and sex-related differences. We analysed data from 4144 individuals with Parkinson’s disease and 370 480 individuals from the general population in the UK Biobank, focusing on four comorbidities with high-quality genome-wide …

What Time Is It? It Is 8 And 1/2 Time: A Rare Case Of Ischemic Stroke Consistent With Eight-And-A-Half Syndrome, Jessica Daza, Marcelo Bedoya-Sommerkamp, Eunbee Cho, Celia Daza, Francisco Gomez, Fatimah Bello, Jia Lin

Faculty, Staff and Student Publications

Eight-and-a-half syndrome is a rare neuro-ophthalmic syndrome characterized by conjugate horizontal gaze palsy, ipsilateral internuclear ophthalmoplegia, and ipsilateral facial nerve palsy. It results from a lesion affecting the paramedian pontine reticular formation, the medial longitudinal fasciculus, and the abducens nucleus of the same side, at the level of the lower pons. We present a case of a 49-year-old man with 2-week diplopia and 3-day right-sided facial droop, drooling, and dysarthria. CT angiography of the head and neck revealed atherosclerotic disease, with decreased caliber of the basilar artery at the level of the pons. Brain MRI showed a subacute ischemic lesion …

Predictors And Outcomes Of Hematoma Expansion And Neurological Decline In Intracerebral Hemorrhage: A Multisite Mobile Stroke Unit Study, Asish K Gulati, Tianwen Ma, Isaiah Rolle, Ryan Peterson, Bianca Pirlog, Justine Chen, Megan Heckathorn, Jonathan Ratcliff, Nicolas Bianchi, Carol Fleming, Michael Frankel, James Grotta, Ritvij Bowry, Stephanie Parker, William Hicks, Digvijaya Navalkele

Faculty, Staff and Student Publications

Background: Hemorrhagic stroke, particularly intracerebral hemorrhage, is one of the leading causes of permanent disability worldwide. Early hematoma expansion (HE) is a key factor in neurological deterioration (ND) and functional outcomes post intracerebral hemorrhage. This observational cohort study examines the predictors and outcomes of HE and ND in spontaneous intracerebral hemorrhage patients using data from 3 Mobile Stroke Units (MSUs) in the United States.

Methods: Patients diagnosed with spontaneous intracerebral hemorrhage within 4 hours of last known well were included. Data collection involved initial and follow-up non-contrast (computerized tomography) CT scans from MSUs and emergency departments, from which the rate …

New Anhydramnios After 22 Weeks And Pulmonary Hypoplasia, Aaron W Roberts, Margaret Clement, Suzanne Marie Lopez, Rita Swinford, Percy Pacora Portella, Edgar Hernandez-Andrade, Matthew Rysavy, Anthony Johnson

Faculty, Staff and Student Publications

Introduction: Anhydramnios due to renal failure prior to 22 weeks of gestational age (WGA) is associated with lethal pulmonary hypoplasia but after 22 WGA outcomes are less clear. We evaluated whether these fetuses, with new anhydramnios after 22 WGA, incur significant risk of severe neonatal pulmonary morbidity.

Methods: This retrospective study of singleton pregnancies diagnosed with new-onset renal anhydramnios after 22 WGA following verifiable normal AFI on ultrasound before 22 WGA from 2021 to 2023. Cases with bilateral renal agenesis, premature rupture of membranes, and nonrenal malformations were excluded.

Results: During the study period 53,698 s trimester ultrasound examinations were …

Impact Of Preoperative And Residual Alpha Angle On Outcomes After Hip Arthroscopy, Jasmine Puria, Daniel Puczko, Christopher S Frey, James L Rogers, Alicia M Hymel, Candler G Mathews Iii, Thomas M Spears, Jaron Paul Sullivan

Faculty, Staff and Student Publications

Purpose: Femoroacetabular impingement syndrome (FAIS) can lead to pain, decreased mobility, and difficulty in performing activities of daily living. Symptoms can improve with surgery, often hip arthroscopy with osteoplasty. Radiological parameters such as the alpha angle can be utilized to determine the degree of cam morphology and assess resection after surgery. This study sought to evaluate the relationship between pre-operative alpha angle and the change in alpha angle on patient satisfaction post-surgical correction using the 12-item International Hip Outcome Tool (iHOT-12).

Patients and methods: Patients that underwent primary or revision hip arthroscopy with osteoplasty for FAIS by a single fellowship-trained …

Information Seeking Behaviors And Attitudes Of Wives Of Former Football Players Regarding Chronic Traumatic Encephalopathy, Summer D Ott, Sukhnandan K Cheema, Alexa Ryder, Philip Schatz, Lorie A Gonzalez, Jecenia Duran, Paul E Schulz

Faculty, Staff and Student Publications

This study examines CTE-related knowledge and information-seeking behaviors of caregivers of persons who are at high risk of CTE. Online survey responses were collected from 64 females, ages 18-74, who were married to former college, semiprofessional, or professional football players and were fluent in English. Ranging from 0 to 18, a score was calculated to represent level of CTE knowledge. Participants were classified into groups based on their spouse's reported symptoms and diagnosis. Approximately 87% of participants reported that their spouses have been diagnosed with a football-related concussion and were significantly more likely to seek out information from a healthcare …

Using Content Validity Index Methodology For Cross-Cultural Translation Of A Patient-Reported Outcome Measure For Head And Neck Cancer, Janet H Van Cleave, Alizendie Guerra, Eva Liang, Carolina Gutiérrez, Ron J Karni, Marcely Tsikis, Geanise Pearl C Nguyen, Allison P Squires

Faculty, Staff and Student Publications

Introduction: Translations of patient-reported measures may not account for structural and cultural differences in shared languages spoken in multiple countries, such as English, Spanish, Arabic, or Russian. The objective of this research was to create a cross-cultural Spanish translation of the New York University (NYU) Electronic Patient Visit Assessment (ePVA)© for head and neck cancer (HNC), a patient-reported symptom measure available only in English.

Methods: Using the Content Validity Index (CVI) methodology, an expert panel of nurses (n = 6) proficient in Spanish and English independently reviewed and rated a forward translation of the ePVA, a measure consisting of …

Molecular, Histologic, And Clinical Characterization Of Methylation Class Pleomorphic Xanthoastrocytoma: An Analysis Of 469 Tumors, Christopher H Dampier, Niharika Shah, Kristyn Galbraith, Azadeh Ebrahimi, Osorio Lopes Abath Neto, Zied Abdullaev, Sanda Alexandrescu, Felipe Andreiuolo, Terri Armstrong, Tiffany Baker, Sahara Cathcart, Hye-Jung Chung, Patrick J Cimino, Kyle S Conway, Jennifer Cotter, Felipe D'Almeida Costa, Karen Dazelle, Nima Etminam, Sima Esther Ferman, Igor Fernandes, Christina K Ferrone, Ahmed Gilani, Mark Gilbert, Jason Gregory, Courtney Ketchum, Han Sung Lee, Ina Lee, Maria Beatriz S Lopes, Qinwen Mao, Michael S Marshall, Matthew Mccord, Stewart G Neill, Jeffrey J Nirschl, Byram H Ozer, Werner Paulus, Marta Penas-Prado, Marco Prinz, Peter Pytel, Martha Quezado, Mark Raffeld, Sharika Rajan, Miriam Ratliff, Guido Reifenberger, Lorraina Robinson, Jens Schittenhelm, Daniel Schrimpf, Omkar Singh, Christian Thomas, Diana Thomas, Jaiyeola Thomas-Ogunniyi, Angus Toland, Rust Turakulov, Rachael Vaubel, Nitin Wadhwani, Jing Wu, Caterina Giannini, Matija Snuderl, Sebastian Brandner, Andreas Von Deimling, Kenneth Aldape

Faculty, Staff and Student Publications

Background: Methylation class pleomorphic xanthoastrocytoma (mcPXA) comprises tumors with the DNA methylation signature of classical PXA but with a wider histologic spectrum, including overlap with glioblastoma (GBM).

Methods: To clarify the histologic and molecular scope of mcPXA and characterize its clinical behavior, a cohort of 469 tumor samples from 458 patients matching to mcPXA by the DKFZ classifier (v12.6 score ≥0.85) was interrogated.

Results: Patient median age was 23 years (range 1-73 years) with a female predominance (259 female/199 male). CDKN2A/B homozygous deletion was observed in 406 of 469 (87%) samples. In samples tested for BRAF p.V600E mutations (n …

New Insights Into Liver Injury And Regeneration From Single-Cell Transcriptomics

Faculty, Staff and Student Publications

Recent advancements in single-cell transcriptomics have significantly enhanced our understanding of acute liver injury (ALI) and regeneration. These technologies enable high-resolution profiling of individual cells, uncovering the diverse and dynamic responses of liver cells to injury. By integrating single-cell RNA sequencing (scRNA-seq) with spatial transcriptomics, researchers have elucidated the complex cellular and molecular mechanisms driving ALI and regeneration processes. This review summarises the platforms and analytical methods of single-cell transcriptomics in liver research and discusses liver sample processing considerations for scRNA-seq, including the comparison between in vivo enzymatic perfusion and ex vivo digestion. It highlights the transformative impact of single-cell …

Haemodynamic Response Of Normal Aortic Valves To Stress Using Invasive, Non-Invasive, And Computational Techniques, Mohamed El Farissi, Pim A L Tonino

Faculty, Staff and Student Publications

AIMS: The haemodynamic physiology of the aortic valve has attracted renewed attention after the introduction of transcatheter aortic valve implantation (TAVI). Understanding normal valve function, especially under stress conditions, permits identification of early pathology and quantification of the extent to which TAVI restores normalcy. We aimed to describe the haemodynamic behaviour of a normal aortic valve during stress via invasive, non-invasive, and computational techniques.

METHODS AND RESULTS: Our cohort included subjects already undergoing invasive coronary angiography for clinical indications. Haemodynamic measurements were made invasively and non-invasively along with dobutamine infusion. Additionally, patient-specific anatomy from computed tomographic imaging served as input …

How Different Is Invasive Coronary Physiology In The Left Anterior Descending Artery?

Faculty, Staff and Student Publications

Given the large amount of myocardium supplied by the left anterior descending (LAD) artery, it understandably receives additional scrutiny during coronary angiography. However, these same features make the interpretation of pressure wire physiology more nuanced to avoid overtreatment. This review provides case examples to underpin an extensive literature review supporting the argument that a "positive" fractional flow reserve (FFR) in the LAD needs to be approached with caution. A large hyperemic gradient, or low FFR, can arise from either a severe and focal lesion in conjunction with low flow or diffuse disease coupled with intact or normal flow. Separating these …

In Utero Alcohol And Tobacco Exposure, Maternal Depression, And Maternal Obesity Are Associated With Impaired Oligodendrocyte Differentiation In The Developing Brain, Emily Sparks, Mary F Morrison, Laura Goetzl, Nune Darbinian, Michael Selzer

Faculty, Staff and Student Publications

Introduction: Fetal alcohol spectrum disorder (FASD) is the leading preventable cause of pediatric cognitive disability and is associated with dysmyelination. We examined possible clinical co-determinants that might interact with EtOH in impairing oligodendrocyte (OL) development. Women who drink, including pregnant women, also disproportionately suffer from depression (mDepression), which we have shown is a risk factor for FASD. Might depression during pregnancy contribute to OL pathology? Maternal obesity (mObesity) also inhibits white matter development in fetal brain. Finally, tobacco exposure inhibits not only OL development, but also the production of structural proteins, such as actin. Our human biobank derived from voluntarily …

Synthetic Versus Biologic Mesh For Complex Open Ventral Hernia Repair: 3-Year Follow-Up Of A Pilot Randomized Controlled Trial, Aris R Arakelians, Connor Hogan, Tunmi Anwoju, Zuhair Ali, Mike K Liang

Faculty, Staff and Student Publications

Background: Biologic mesh is often used in complex hernia repair, but there has been limited clinical evidence to date to support this practice. The aim of this study was to compare clinical and patient-reported outcomes of biologic versus synthetic mesh for complex open ventral hernia repair (OVHR) at 3 years.

Methods: Patients from a single center, randomized, controlled, pilot trial comparing biologic versus synthetic mesh in complex OVHR were followed for 3 years. The primary outcome focused on major complications, namely mesh infections, hernia recurrences, reoperations, and deaths. Secondary outcomes included surgical site infections, surgical site occurrences, and patient-reported outcomes. …

Prenatal Alcohol Exposure Inhibits Transient Expression Of Autophagy And Synaptic Proteins In Developing Brain, Jamal Hamze, Shohreh Amini, Laura Goetzl, Michael E Selzer

Faculty, Staff and Student Publications

Introduction: Neuronal apoptosis and consequent inhibition of autophagy, with loss of synaptic connections are central events in the genesis of fetal alcohol spectrum disorders (FASD). However, studies of molecular mechanisms of autophagy in human fetal brain are limited. Recently, prenatal exposure to EtOH was associated with reduced miRNA-9 levels in fetal brain-derived exosomes (FB- Es) isolated from maternal plasma, which correlated with small eyes, an anatomical hallmark of fetal alcohol syndrome (FAS). Since miR-9 targets several genes that regulate synaptic plasticity, EtOH-induced inhibition of miR-9 could potentially result in dysregulation of genes involved in synaptogenesis/plasticity.

Methods: Rats were fed a …

Limitations Of The Radiotheranostic Concept In Neuroendocrine Tumors Due To Lineage-Dependent Somatostatin Receptor Expression On Hematopoietic Stem And Progenitor Cells, Sukhen Ghosh, Ali Azhdarinia, Wolfgang A Weber, Katharina S Götze, Susanne Kossatz

Faculty, Staff and Student Publications

Rationale: Radiopharmaceutical therapy (RPT) has become an effective treatment option for neuroendocrine tumors (NETs) and castration-resistant prostate cancer and is in clinical development for many indications. One of the major advantages of theranostic RPT is that the distribution of radiopharmaceuticals in the human body can be imaged, and radiation doses to the patient's organs can be calculated. However, accurate dosimetry may be fundamentally limited by microscopic heterogeneity of radiopharmaceutical distribution.

Methods: We developed fluorescent analogs of somatostatin-receptor-subtype 2 (SSTR2) targeting Lutetium-177 labeled radiopharmaceuticals that are clinically used in patients with NETs and studied their uptake by hematopoietic stem and progenitor …

Mmrt: Multimut Recursive Tree For Predicting Functional Effects Of High-Order Protein Variants From Low-Order Variants

Faculty, Staff and Student Publications

Protein sequences primarily determine their stability and functions. Mutations may occur at one, two, or three positions at the same time (low-order variants) or at multiple positions simultaneously (high-order variants), which affect protein functions. So far, low-order variants, such as single variants, double variants, and triple variants, have been well-studied through high-throughput experimental scanning techniques and computational prediction methods. However, research on high-order variants remains limited because of the difficulty of scanning an exponentially large number of potential variant combinations. Nonetheless, studying higher-order variants is crucial for understanding the pathogenesis of complex diseases, advancing protein engineering, and driving precision medicine. …

Enhancing The Utility Of Polygenic Scores In Alzheimer’S Disease Through Systematic Curation And Annotation

Faculty, Staff and Student Publications

Introduction: Polygenic Scores (PGSs) assess cumulative genetic risk variants that contribute to the association with complex diseases like Alzheimer's Disease (AD). The PGS Catalog is a valuable repository of PGSs of various complex diseases, but it lacks standardized annotations and harmonization, making the information difficult to integrate for a specific disease.

Methods: In this study, we curated 44 PGS datasets for AD from the PGS Catalog, categorized them into five methodological groups, and annotated 813,257 variants to nearby genes. We aligned the scores based on the "GWAS significant variants" (GWAS-SV) method with the GWAS Catalog and flagged redundant files and …