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Full-Text Articles in Entire DC Network
Wearable Sensor Technology And Biomechanical Gait Analysis In Post-Stroke Rehabilitation: A Review With Implications For The Saudi Healthcare System, Abdullah H. Alzahrani
Wearable Sensor Technology And Biomechanical Gait Analysis In Post-Stroke Rehabilitation: A Review With Implications For The Saudi Healthcare System, Abdullah H. Alzahrani
Neurosciences
Stroke remains a major cause of disability worldwide, with gait impairment affecting up to 80% of survivors and contributing to long-term dependence, fall risk, and reduced quality of life. In Saudi Arabia, stroke incidence is rising, with a significant burden on younger populations and disparities in access to post-stroke rehabilitation services. Conventional gait analysis tools rely on expensive, specialized laboratory equipment, which limits their availability in low-resource and rural settings. Recent advances in wearable sensor technologies, including inertial measurement units, pressure insoles, and electromyography systems, offer portable, scalable, and cost-efficient options for assessing gait in real-world environments. These systems can …
Efficacy And Safety Of Plasma Exchange And Immunoadsorption For Acute Optic Neuritis In Patients With Demyelinating Diseases: A Systematic Review And Meta-Analysis, Mehenaz A Hanbazazh, Mohammed Ridha Algethami, Abdulwahhab Omar Anbarserry, Ruba Mohammed Alghanmi, Lama Nawaf Alanazi, Ahmed Ayed N Alanazi, Bashaier Gubran Alqahtani, Mohammed Abdullah Alamri
Efficacy And Safety Of Plasma Exchange And Immunoadsorption For Acute Optic Neuritis In Patients With Demyelinating Diseases: A Systematic Review And Meta-Analysis, Mehenaz A Hanbazazh, Mohammed Ridha Algethami, Abdulwahhab Omar Anbarserry, Ruba Mohammed Alghanmi, Lama Nawaf Alanazi, Ahmed Ayed N Alanazi, Bashaier Gubran Alqahtani, Mohammed Abdullah Alamri
Neurosciences
Background: Optic neuritis (ON), a common manifestation of demyelinating disorders such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often leads to significant visual impairment. Although high-dose corticosteroids are a first-line therapy, many patients experience incomplete recovery. Apheresis therapies, including plasma exchange (PLEX) and immunoadsorption (IA), are being increasingly used as rescue treatments, but their efficacy and safety are debated.
Methods: We conducted a systematic review and meta-analysis of studies evaluating PLEX and IA for acute ON in patients with demyelinating diseases. Four databases were searched up to January 2025. The included …
Investigating The Patent Foramen Ovale–Migraine Link In Southern Saudi Arabia, Al-Amir Bassiouny Mohamed, Maeed Alkathiri, Saad Mushabab Ali Alqahtani, Naif H. Ali, Saima Kashif, Saad A. Alshahrani, Mohammed S. Alqahtani, Mohamed Gaber Mahmoud Gabr, Eltohami Zydan Dafalla, Basharat Hameed Zargar, Wael Qenawi, Ali Mohammed A. Alshehri, Fatimah Asiri, Ahmed Borai
Investigating The Patent Foramen Ovale–Migraine Link In Southern Saudi Arabia, Al-Amir Bassiouny Mohamed, Maeed Alkathiri, Saad Mushabab Ali Alqahtani, Naif H. Ali, Saima Kashif, Saad A. Alshahrani, Mohammed S. Alqahtani, Mohamed Gaber Mahmoud Gabr, Eltohami Zydan Dafalla, Basharat Hameed Zargar, Wael Qenawi, Ali Mohammed A. Alshehri, Fatimah Asiri, Ahmed Borai
Neurosciences
Objective: Migraine is a highly disabling neurological condition, and increasing attention has focused on a possible connection with patent foramen ovale (PFO).
Methods: This single-center observational study enrolled 45 individuals from January to April 2024: 30 migraine patients with PFO (Group 1) and 15 migraine patients without PFO serving as controls (Group 2). All subjects underwent transthoracic echocardiography and completed standardized instruments including the Migraine Disability Assessment (MIDAS), Headache Impact Test (HIT-6), Migraine Symptom Severity Scale (MSSS), Allodynia Symptom Checklist (ASC-12), Visual Aura Rating Scale (VARS), and Migraine Treatment Optimization Questionnaire (mTOQ-6).
Results: The participant's mean age was 37.3 ± …
Plasma Gdf15 Affects Long-Term Dementia Risk And Alters Neuroimmune Signaling, Cassandra O Blew, Michael R Duggan, Dimitrios Tsitsipatis, Gabriela T Gomez, Zulema Rodriguez-Hernandez, Luke C Pilling, Jingsha Chen, Eva Jacobsen, Heather E Dark, Yifei Lu, Shannon M Drouin, Cassandra M Joynes, Minhao Yao, Murat Bilgel, Abhay Moghekar, Qu Tian, Julián Candia, Mary Kaileh, Aditi Gupta, Krystyna Mazan-Mamczarz, Myriam Gorospe, Alexey Lyashkov, Yevgeniya Lukyanenko, Mika Kivimaki, Philipp Frank, Lori L Jennings, Valborg Gudmundsdottir, Vilmundur Gudnason, Lenore J Launer, Naoto Kaneko, Shintaro Kato, Makio Furuichi, Masaki Shibayama, Masahisa Katsuno, Keita Hiraga, Yukiko Nishita, Rei Otsuka, James R Pike, Mary R Rooney, Pascal Schlosser, Yuhan Cui, Guray Erus, Christos Davatzikos, Rebecca F Gottesman, Iwao Waga, Priya Palta, Christie Ballantyne, Michael Griswold, Zhonghua Liu, Luigi Ferrucci, Allison B Herman, Keenan A Walker
Plasma Gdf15 Affects Long-Term Dementia Risk And Alters Neuroimmune Signaling, Cassandra O Blew, Michael R Duggan, Dimitrios Tsitsipatis, Gabriela T Gomez, Zulema Rodriguez-Hernandez, Luke C Pilling, Jingsha Chen, Eva Jacobsen, Heather E Dark, Yifei Lu, Shannon M Drouin, Cassandra M Joynes, Minhao Yao, Murat Bilgel, Abhay Moghekar, Qu Tian, Julián Candia, Mary Kaileh, Aditi Gupta, Krystyna Mazan-Mamczarz, Myriam Gorospe, Alexey Lyashkov, Yevgeniya Lukyanenko, Mika Kivimaki, Philipp Frank, Lori L Jennings, Valborg Gudmundsdottir, Vilmundur Gudnason, Lenore J Launer, Naoto Kaneko, Shintaro Kato, Makio Furuichi, Masaki Shibayama, Masahisa Katsuno, Keita Hiraga, Yukiko Nishita, Rei Otsuka, James R Pike, Mary R Rooney, Pascal Schlosser, Yuhan Cui, Guray Erus, Christos Davatzikos, Rebecca F Gottesman, Iwao Waga, Priya Palta, Christie Ballantyne, Michael Griswold, Zhonghua Liu, Luigi Ferrucci, Allison B Herman, Keenan A Walker
Faculty, Staff and Students Publications
Growth/differentiation factor-15 (GDF15) is a secreted cytokine strongly associated with dementia risk. However, the extent to which GDF15 represents a biomarker and driver of dementia risk remains unclear. Across multiple cohorts, we demonstrated that plasma GDF15 is associated with greater dementia risk over 15- to 25-year follow-up periods when measured in midlife, with stronger associations observed for vascular, compared to Alzheimer's disease (AD), dementia. Two-sample Mendelian randomization supported plasma GDF15's mechanistic role in AD and related dementias, while cohort studies linked it to cerebral small vessel disease, neurodegeneration, phosphorylated tau, and a cerebrospinal fluid proteomic signature indicative of neuroimmune activation. …
Early-Stage Corticostriatal Hyperactivity Impairs Cognitive Flexibility Alongside Striatal Cholinergic Dysfunction In An Alzheimer's Disease Model, Yufei Huang, Xueyi Xie, Zhenbo Huang, Ruifeng Chen, Himanshu Gangal, Xuehua Wang, Karienn Souza, Julia Hunter, Xin Wu, Doodipala Samba Reddy, Jeannie Chin, Jun Wang
Early-Stage Corticostriatal Hyperactivity Impairs Cognitive Flexibility Alongside Striatal Cholinergic Dysfunction In An Alzheimer's Disease Model, Yufei Huang, Xueyi Xie, Zhenbo Huang, Ruifeng Chen, Himanshu Gangal, Xuehua Wang, Karienn Souza, Julia Hunter, Xin Wu, Doodipala Samba Reddy, Jeannie Chin, Jun Wang
Faculty, Staff and Students Publications
Cognitive flexibility declines early in Alzheimer's disease, yet the underlying circuit mechanisms remain unknown. Here, we report that young 5xFAD mice exhibit deficits in instrumental reversal learning prior to spatial memory impairment. This behavioral inflexibility is associated with abnormal neuronal reactivation in the medial prefrontal cortex and dorsomedial striatum. Electrophysiological recordings reveal that medial prefrontal cortex neurons are hyperexcitable and receive increased excitatory input. Furthermore, glutamatergic transmission from the medial prefrontal cortex to striatal direct-pathway medium spiny neurons is enhanced and coincides with strengthened inhibitory transmission onto striatal cholinergic interneurons, reduced spontaneous firing, and diminished striatal acetylcholine release. Critically, sustained …
Human Milk Small Extracellular Vesicles Elicit Changes In Inflammatory Response In Infant Human Intestinal Enteroids, Kacie D Waiters, Anthony S Peidl, Hailey A Mcandrew, Ashfia F Khan, Grace Adeniyi-Ipadeola, Hephzibah Nwanosike, Sana Sharif, M Funmi Babajide, Micah Castillo, Preethi H Gunaratne, Samaneh Karami, Hoa Nguyen-Phuc, Xinli Liu, Sasirekha Ramani, Tasneem Bawa-Khalfe
Human Milk Small Extracellular Vesicles Elicit Changes In Inflammatory Response In Infant Human Intestinal Enteroids, Kacie D Waiters, Anthony S Peidl, Hailey A Mcandrew, Ashfia F Khan, Grace Adeniyi-Ipadeola, Hephzibah Nwanosike, Sana Sharif, M Funmi Babajide, Micah Castillo, Preethi H Gunaratne, Samaneh Karami, Hoa Nguyen-Phuc, Xinli Liu, Sasirekha Ramani, Tasneem Bawa-Khalfe
Faculty, Staff and Students Publications
Human milk (HM) is the key nutritional source for infants and the most effective preventative approach against serious gastrointestinal inflammatory diseases like necrotizing enterocolitis (NEC) in preterm infants. Numerous studies in animal models indicate HM-derived small extracellular vesicles (HMEV) reduce severity of inflammation; however, data on human-specific models are limited. Isolated HMEV were characterized from early-HM (colostrum and transitional), mature-HM, and a combined, pasteurized donor bank-like HM sample (pool-); pool-HMEV retains a profile aligned with HMEV from both early- and mature-HM samples. Exposure to pool-HMEV initiates unique gene signatures associated with reduction of inflammation including NFkB-driven TNFα signaling in human …
Adaptation Of The Transition Readiness Assessment Questionnaire For Pediatric-Onset Multiple Sclerosis: Protocol For A User-Centered Design Approach, Claudia Gambrah-Lyles, Aaron W Abrams, Sara Loud, Hollie Schmidt, Emily Blosberg, Melissa Wright, Kelsey E Poisson, Kristen S Fisher, Kimberly A O'Neill, Akash Virupakshaiah, John W Rose
Adaptation Of The Transition Readiness Assessment Questionnaire For Pediatric-Onset Multiple Sclerosis: Protocol For A User-Centered Design Approach, Claudia Gambrah-Lyles, Aaron W Abrams, Sara Loud, Hollie Schmidt, Emily Blosberg, Melissa Wright, Kelsey E Poisson, Kristen S Fisher, Kimberly A O'Neill, Akash Virupakshaiah, John W Rose
Faculty, Staff and Students Publications
Background: Pediatric-onset multiple sclerosis (POMS) is a chronic, progressive neurologic condition requiring lifelong management and coordinated transition from pediatric to adult care. Evidence-based guidelines identify transition readiness assessment as a core component of successful transition; however, most POMS clinics do not formally assess readiness, and existing tools do not address POMS-specific challenges, such as fluctuating disability, complex treatment regimens, and cognitive impairment. This gap underscores the need for a transition readiness measure tailored to POMS.
Objective: This paper aims to describe a stakeholder-engaged, implementation science-guided protocol for adapting the Transition Readiness Assessment Questionnaire (TRAQ) version 6.0 to reflect the unique …
Evaluating The Reproducibility And Verifiability Of Nutrition Research: A Case Study Of Studies Assessing The Relationship Between Potatoes And Colorectal Cancer, Yasaman Jamshidi-Naeini, Colby J Vorland, Pranav Kapoor, Bailey Ortyl, Jocelyn Mineo, Luke Still, Korlu Sorsor, Shelby Rodney, Xander Tooze, Brent Flickinger, Beate Henschel, Stephanie L Dickinson, David B Allison
Evaluating The Reproducibility And Verifiability Of Nutrition Research: A Case Study Of Studies Assessing The Relationship Between Potatoes And Colorectal Cancer, Yasaman Jamshidi-Naeini, Colby J Vorland, Pranav Kapoor, Bailey Ortyl, Jocelyn Mineo, Luke Still, Korlu Sorsor, Shelby Rodney, Xander Tooze, Brent Flickinger, Beate Henschel, Stephanie L Dickinson, David B Allison
Faculty, Staff and Students Publications
The credibility of nutritional research is dependent on the rigor with which studies are conducted and the ability for independent assessment to be performed. Despite the importance of these, more work is needed in the field of nutrition to buttress the trustworthiness of nutrition research. To develop and apply a process for evaluating the rigor, reproducibility, and verifiability of nutritional research, using the relationship between potato consumption and Colorectal Cancer (CRC) as a case study. We updated existing systematic reviews to include studies on potatoes and CRC, assessing their design, execution, and reporting quality. We attempted to reproduce and verify …
Self-Perceived Burden And Mental Health Outcomes In Adults With Osteogenesis Imperfecta, Emily R Strouphauer, Camille Villar, Ryan J Mccarty, Danqi Li, Gianna M Colombo, Brendan Lee, Chaya N Murali, Dianne Nguyen, Sarah Sadek, Marie-Eve Robinson, Jocelyn Gomez, Michelle Fynan, V Reid Sutton, Andrew D Wiese, Eric A Storch
Self-Perceived Burden And Mental Health Outcomes In Adults With Osteogenesis Imperfecta, Emily R Strouphauer, Camille Villar, Ryan J Mccarty, Danqi Li, Gianna M Colombo, Brendan Lee, Chaya N Murali, Dianne Nguyen, Sarah Sadek, Marie-Eve Robinson, Jocelyn Gomez, Michelle Fynan, V Reid Sutton, Andrew D Wiese, Eric A Storch
Faculty, Staff and Students Publications
Osteogenesis Imperfecta (OI) is a rare disorder causing bone fragility, pain, and functional impairment that causes substantial psychosocial burden. This study examined how self-perceived burden (SPB), or distress from feelings of dependence on caregivers, relates to depression, anxiety, and suicidality in adults with OI. A total of 208 adults (M age = 42.9, predominately White and female) with OI were recruited to complete a cross-sectional survey assessing SPB, psychological symptoms, health, and sociodemographics. Results indicated that SPB was significantly higher among younger individuals, those not living with a partner, those living with adult family members, lower-income groups, and individuals …
Point-Of-Care Hrhpv Mrna Detection With Reverse Transcription Recombinase Polymerase Amplification On A Portable Fluorimeter From Provider-Collected Cervical Samples In Maputo, Mozambique, Emilie Newsham Novak, Cannon J Hansen, Zoha Wazir, Ariel Ma, Jennifer Carns, Hira Atif, Jane R Montealegre, Michael E Scheurer, Cesaltina Lorenzoni, Daniel G Rosen, Mila P Salcedo, Kathleen M Schmeler, Rebecca R Richards-Kortum
Point-Of-Care Hrhpv Mrna Detection With Reverse Transcription Recombinase Polymerase Amplification On A Portable Fluorimeter From Provider-Collected Cervical Samples In Maputo, Mozambique, Emilie Newsham Novak, Cannon J Hansen, Zoha Wazir, Ariel Ma, Jennifer Carns, Hira Atif, Jane R Montealegre, Michael E Scheurer, Cesaltina Lorenzoni, Daniel G Rosen, Mila P Salcedo, Kathleen M Schmeler, Rebecca R Richards-Kortum
Faculty, Staff and Students Publications
Background: Cervical cancer is the most common cancer in women in Mozambique, where limited screening infrastructure contributes to high disease burden. While testing for high-risk human papillomavirus (hrHPV) DNA can identify women at risk for cervical cancer, its limited specificity may lead to overtreatment in screen-and-treat programs, straining resources. We performed a pilot study to evaluate preliminary feasibility of a novel, accessible test to detect hrHPV mRNA, a more specific biomarker for cervical cancer risk, from 22 women who previously screened positive for visual inspection with acetic acid at Maputo Central Hospital in Mozambique.
Methods: Cervicovaginal samples were analyzed for …
Microglial Swell1 Deficiency Drives Male-Specific Seizure Vulnerability But Paradoxical Neuroprotection Through Impaired Phagocytosis, Abhijeet S Barath, Aastha Dheer, Laura Montier, Mekenzie M Peshoff, Emily Dale, Flavia Goche, Thanh Thanh Le Nguyen, Mastura Akter, Fangfang Qi, Dimitrios Kleidonas, Lauren Harris, Sarah A Jewanee, Anthony D Umpierre, Dale B Bosco, Koichiro Haruwaka, Rajan Sah, Long-Jun Wu, Rongzhuo Hua, Tejaswani Datla
Microglial Swell1 Deficiency Drives Male-Specific Seizure Vulnerability But Paradoxical Neuroprotection Through Impaired Phagocytosis, Abhijeet S Barath, Aastha Dheer, Laura Montier, Mekenzie M Peshoff, Emily Dale, Flavia Goche, Thanh Thanh Le Nguyen, Mastura Akter, Fangfang Qi, Dimitrios Kleidonas, Lauren Harris, Sarah A Jewanee, Anthony D Umpierre, Dale B Bosco, Koichiro Haruwaka, Rajan Sah, Long-Jun Wu, Rongzhuo Hua, Tejaswani Datla
The Brown Foundation: Institute of Molecular Medicine
The discovery of genes encoding the volume-regulated anion channel (VRAC) has enabled detailed exploration of its cell type-specific roles in the brain. LRRC8A (SWELL1) is the essential VRAC subunit. We observed seizure-induced, subunit-specific changes in microglial VRAC expression and investigated its function using conditional KO (cKO) of LRRC8A in microglia. SWELL1 cKO mice exhibited a male-specific increase in kainate-induced seizure severity, yet showed paradoxical neuroprotection against seizure-associated neuronal loss. Mechanistically, SWELL1 deletion led to a cell-autonomous reduction in microglial density and decreased release of VRAC-permeable neuroactive metabolites, including taurine, GABA, and glutamate in culture. Additionally, impaired phagocytic kinetics and reduced …
An Inf2-Dependent Actin-Mediated Step In Inositol 1,4,5-Trisphosphate Receptor Cluster Formation And Activity, Maite R. Zavala, Amrapali Ghosh, Suresh K. Joseph, Rajarshi Chakrabarti
An Inf2-Dependent Actin-Mediated Step In Inositol 1,4,5-Trisphosphate Receptor Cluster Formation And Activity, Maite R. Zavala, Amrapali Ghosh, Suresh K. Joseph, Rajarshi Chakrabarti
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Intracellular calcium signaling plays a vital role in regulating various cellular processes including gene regulation, motility, metabolism, and cell death. Inositol 1,4,5-trisphosphate receptors (IP3Rs) on the endoplasmic reticulum (ER) are a major cation channel that regulates stimulus-induced calcium release from the ER. While several molecular players regulate the activity of IP3R, its regulation by actin filaments was uncharacterized. Here, we show that actin filaments polymerized by the specific actin nucleator INF2 facilitate agonist-induced IP3R activity. Our results demonstrate that INF2-mediated actin filaments regulate the formation and/or stability of IP3R clusters on the ER that have been previously shown to be …
A Multilevel Analysis Of Hiv Care Outcomes Across Age, Race, And Housing Among United States Women Veterans, Giselle Day, Amber B Amspoker, Alan Z Sheinfil, Liang Chen, Emmanuel Guajardo, Maria E Fernandez, Cici Bauer, Irene Tamí-Maury, Jan Lindsay
A Multilevel Analysis Of Hiv Care Outcomes Across Age, Race, And Housing Among United States Women Veterans, Giselle Day, Amber B Amspoker, Alan Z Sheinfil, Liang Chen, Emmanuel Guajardo, Maria E Fernandez, Cici Bauer, Irene Tamí-Maury, Jan Lindsay
Faculty, Staff and Students Publications
Background: Women veterans with HIV represent a growing, diverse population within the Veterans Health Administration (VHA). This study examined HIV care continuum outcomes among women veterans using a multilevel intersectional approach.
Methods: We conducted a retrospective analysis of 1154 women veterans with HIV in VHA care in fiscal year 2022, with outcomes assessed in fiscal year 2023. We applied Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) to evaluate how combinations of social positions (age, race/ethnicity, housing status) were associated with HIV outcomes.
Results: MAIHDA models showed that younger age (< 45 years) and being unhoused were consistently associated with lower odds of care engagement and viral suppression than midlife (45-64) and older (65+) housed women veterans. Additionally, predicted probability analyses revealed distinct clustering patterns. Younger non-Hispanic White women consistently ranked among the lowest performing strata across all outcomes, while midlife and older Hispanic and non-Hispanic Black women veterans clustered among the highest. Variance Partition Coefficients from null models were modest (1.8-3.0%). Fully adjusted models showed no remaining between-stratum variance, suggesting that the included social positions explained the observed differences in our dataset.
Conclusions: These findings highlight disparities in HIV care …
Using United States Medicare Program Claims To Identify Reliable Measures Of Low Value Services Influenced By Primary Care Physician Decisions, Chris Fleming, Dmitriy Poznyak, Rhea E. Powell, Claire Erba, Eunhae Shin, Rui Wang, Claire Burkhart, Arkadipta Ghosh, Eugene C. Rich
Using United States Medicare Program Claims To Identify Reliable Measures Of Low Value Services Influenced By Primary Care Physician Decisions, Chris Fleming, Dmitriy Poznyak, Rhea E. Powell, Claire Erba, Eunhae Shin, Rui Wang, Claire Burkhart, Arkadipta Ghosh, Eugene C. Rich
Division of Internal Medicine Faculty Papers & Presentations
BACKGROUND: Low-value services (LVS) are those that “… provide little to no benefit to patients….”1 Among an existing set of 31 LVS are invasive procedures not typically performed by primary care physicians (PCPs), and other LVS that may be commonly provided by specialists. To facilitate research on the role of primary care physicians in low-value care, we sought to identify the reliability of two subsets of LVS measures that are more directly subject to PCPs’ decisions. We refer to these as primary care adjacent (“PCA”) LVS measures.
METHODS: Retrospective observational cohort study to identify which of a 31-item LVS …
Targeted Inhibition Of Atr Kinase Promotes Antitumor Immunity In Hnscc Through Enhanced Sting Activation And T Cell Function, Fabio Hb Da Costa, Mutsuki Kawabe, Tsung-You Tsai, Kento Okamoto, Mason D Bartels, Sofia Cortes, Ratna Veeramachaneni, Roberto Rangel, Mitchell J Frederick, Vlad C Sandulache, Andrew G Sikora, Jeffrey N Myers, Abdullah A Osman
Targeted Inhibition Of Atr Kinase Promotes Antitumor Immunity In Hnscc Through Enhanced Sting Activation And T Cell Function, Fabio Hb Da Costa, Mutsuki Kawabe, Tsung-You Tsai, Kento Okamoto, Mason D Bartels, Sofia Cortes, Ratna Veeramachaneni, Roberto Rangel, Mitchell J Frederick, Vlad C Sandulache, Andrew G Sikora, Jeffrey N Myers, Abdullah A Osman
Faculty, Staff and Students Publications
Objectives: Oral cavity head and neck squamous cell carcinoma (HNSCC) represents a major global health burden, with over 40,000 new cases annually in the United States and >500,000 worldwide. Despite advances in surgery, radiation therapy, chemotherapy, and immunotherapy, overall survival rates have remained largely stagnant over the past three decades, and over half of patients ultimately die from the disease. Although immune checkpoint inhibitors (ICIs) have improved outcomes for a subset of patients with recurrent or metastatic HNSCC, the majority gain limited benefit. Thus, novel therapeutic strategies that enhance responses to immunotherapy are urgently needed. The ATR-CHK1 signaling pathway has …
Protocol For Purifying And Sequencing Cell Subpopulations Based On Rna Fish Signal In Planaria, Mary Cathleen Mckinney, Jason A Morrison, Frederick G Mann, Dung M Vuu, Carolyn E Brewster, Kate E Hall, Blair W Benham-Pyle, Alejandro Sánchez Alvarado
Protocol For Purifying And Sequencing Cell Subpopulations Based On Rna Fish Signal In Planaria, Mary Cathleen Mckinney, Jason A Morrison, Frederick G Mann, Dung M Vuu, Carolyn E Brewster, Kate E Hall, Blair W Benham-Pyle, Alejandro Sánchez Alvarado
Faculty, Staff and Students Publications
Isolation and characterization of rare cell types in non-model organisms present a challenge. Here, we provide a protocol to purify specific cells from planaria for downstream RNA sequencing. We employ a one-step dissociation and fixation method that avoids RNA-degrading formaldehyde. We label cells using RNA fluorescence in situ hybridization (RNA FISH) and flow sort to enrich sequencing reads from cells of interest for deeper biological insight.
For complete details on the use and execution of this protocol, please refer to Mann et al.1
Neddylation Maintains Oocyte Quality By Stabilizing Mitochondrial Transcription, Avery A Ahmed, Tessa E Steenwinkel, Bethany K Patton, Peixin Jiang, Matthew D Meyer, Jaspreet K Rishi, Mei Leng, Alexander B Saltzman, Elizabeth S Anaya, Momal Sharif, Laurie J Mckenzie, Laura Detti, Anna Malovannaya, Sean M Hartig, Stephanie A Pangas
Neddylation Maintains Oocyte Quality By Stabilizing Mitochondrial Transcription, Avery A Ahmed, Tessa E Steenwinkel, Bethany K Patton, Peixin Jiang, Matthew D Meyer, Jaspreet K Rishi, Mei Leng, Alexander B Saltzman, Elizabeth S Anaya, Momal Sharif, Laurie J Mckenzie, Laura Detti, Anna Malovannaya, Sean M Hartig, Stephanie A Pangas
Faculty, Staff and Students Publications
Age-related decline in oocyte quality increases the risk of infertility, miscarriage, and birth defects. Mitochondrial dysfunction is a key contributor to this decline. Here, we report that oocyte-specific deletion of Uba3, which encodes the catalytic subunit of the E1 NEDDylation-activating complex, causes sterility in mice. Fully grown, germinal vesicle–stage Uba3 conditional knockout oocytes exhibit mitochondrial dysfunction, including elevated reactive oxygen species, impaired oxidative phosphorylation, and depletion of mitochondrially encoded RNA transcripts. Proteomic analysis identified alterations in mitochondrial-associated proteins, including enrichment of mitochondrial matrix and respiratory chain components and reduced abundance of electron transport chain complexes. These defects were associated …
Conformational Cycling Of The Wntless Transporter Drives Trafficking And Secretion Of Wnt Morphogens, Yunhui Ge, Taciani De Almeida Magalhaes, Hongjiang Wu, Dick J H Van Den Boomen, Thu Uyen Nguyen, Tongyi Dou, Gaya P Yadav, Sukyeong Lee, Zhao Wang, Andrew Lemoff, Xuemei Luo, Sumitha S Menon, Min Zhang, Jin Wang, Zhicheng Jin, Jiansen Jiang, Adrian Salic, Pengxiang Huang
Conformational Cycling Of The Wntless Transporter Drives Trafficking And Secretion Of Wnt Morphogens, Yunhui Ge, Taciani De Almeida Magalhaes, Hongjiang Wu, Dick J H Van Den Boomen, Thu Uyen Nguyen, Tongyi Dou, Gaya P Yadav, Sukyeong Lee, Zhao Wang, Andrew Lemoff, Xuemei Luo, Sumitha S Menon, Min Zhang, Jin Wang, Zhicheng Jin, Jiansen Jiang, Adrian Salic, Pengxiang Huang
Faculty, Staff and Students Publications
Wnt proteins are lipid-modified morphogens fundamental in development and disease. During Wnt biogenesis, the G-protein-coupled receptor (GPCR)-like transporter Wntless (WLS) escorts lipidated Wnts from the endoplasmic reticulum to the plasma membrane, then transfers them to extracellular carriers, forming active and soluble morphogen-carrier complexes. To dissect the mechanisms involved, we solve cryo-EM structures of Wnt-bound WLS and unliganded WLS, and perform structure-guided functional experiments. Wnts engage WLS via three conserved hairpins, which are all required for Wnt trafficking to the cell surface and carrier-mediated secretion. Wnt release from cells is driven by dramatic conformational changes in the WLS transmembrane domain, reminiscent …
3d Em Uncovers Mitochondrial Network Remodeling In Residual Triple Negative Breast Cancer After Conventional Chemotherapy Treatments, Mariah J Berner, Heather K Beasley, Benjamin Rodriguez, Audra Lane, Steven W Wall, Andrea G Marshall, Zer Vue, Larry Vang, Mokryun L Baek, Mason Killion, Faben Zeleke, Bryanna Shao, Dominique Parker, Autumn Peterson, Julie Sterling Rhoades, Lacey E Dobrolecki, Amber Crabtree, Annet Kirabo, Sepiso K Masenga, Prasanna Katti, Prasanna Venkhatesh, Chandravanu Dash, Michael T Lewis, Antentor Hinton, Gloria V Echeverria
3d Em Uncovers Mitochondrial Network Remodeling In Residual Triple Negative Breast Cancer After Conventional Chemotherapy Treatments, Mariah J Berner, Heather K Beasley, Benjamin Rodriguez, Audra Lane, Steven W Wall, Andrea G Marshall, Zer Vue, Larry Vang, Mokryun L Baek, Mason Killion, Faben Zeleke, Bryanna Shao, Dominique Parker, Autumn Peterson, Julie Sterling Rhoades, Lacey E Dobrolecki, Amber Crabtree, Annet Kirabo, Sepiso K Masenga, Prasanna Katti, Prasanna Venkhatesh, Chandravanu Dash, Michael T Lewis, Antentor Hinton, Gloria V Echeverria
Faculty, Staff and Students Publications
Mitochondria are hubs of metabolism and signaling. We previously demonstrated the importance of mitochondrial structure and function in chemotherapy-refractory triple-negative breast cancer (TNBC). Herein, we present the first 3D analysis of mitochondrial networks in human tumor tissues. Using serial block face scanning electron microscopy, we reconstructed 3,750 mitochondria and 800 lipid droplets (LDs) in naive and residual tumors persisting after conventional chemotherapies in two orthotopic patient-derived xenografts (PDX). Chemotherapies administered as monotherapy or in combination produced residual tumors that harbored mitochondria with significantly increased areas, volumes, and perimeters. We observed substantial reduction of mitochondrial intratumor heterogeneity following all treatments. Further, …
Targeting Arginine Metabolism Overcomes Chemotherapy Resistance In Aggressive-Variant Prostate Cancers, Elavarasan Subramani, Patrick G Pilié, Rebecca Slack-Tidwell, Paul V Viscuse, Xianghong Kuang, Thirukumaran Kandasamy, Dominik Awad, Jenny J Han, Licai Huang, Christine B Peterson, Amado J Zurita, Sumit K Subudhi, Paul G Corn, Rama Soundararajan, Peter Shepherd, Badrajee Piyarathna, Vasanta Putluri, Nagireddy Putluri, Arun Sreekumar, Yuzhuo Wang, Amina Zoubeidi, Iqbal Mahmud, Sara A Martinez, Lin Tan, Philip L Lorenzi, Sreyashi Basu, Sonali Jindal, Padmanee Sharma, Christopher J Logothetis, Timothy C Thompson, Daniel E Frigo, Ana M Aparicio
Targeting Arginine Metabolism Overcomes Chemotherapy Resistance In Aggressive-Variant Prostate Cancers, Elavarasan Subramani, Patrick G Pilié, Rebecca Slack-Tidwell, Paul V Viscuse, Xianghong Kuang, Thirukumaran Kandasamy, Dominik Awad, Jenny J Han, Licai Huang, Christine B Peterson, Amado J Zurita, Sumit K Subudhi, Paul G Corn, Rama Soundararajan, Peter Shepherd, Badrajee Piyarathna, Vasanta Putluri, Nagireddy Putluri, Arun Sreekumar, Yuzhuo Wang, Amina Zoubeidi, Iqbal Mahmud, Sara A Martinez, Lin Tan, Philip L Lorenzi, Sreyashi Basu, Sonali Jindal, Padmanee Sharma, Christopher J Logothetis, Timothy C Thompson, Daniel E Frigo, Ana M Aparicio
Faculty, Staff and Students Publications
Aggressive-variant prostate cancers (AVPCs) respond poorly to anti-androgen therapy but show sensitivity to taxane-platinum chemotherapy, though outcomes remain poor. We conducted a phase 2 trial testing induction cabazitaxel plus carboplatin (CabCarb) followed by olaparib maintenance versus observation in men with AVPC. The primary endpoint of improved progression-free survival (PFS) was not met, likely due to the study being underpowered after 38.5% of patients experienced early progression (ChemoPD) prior to randomization. No genomic alterations predicted ChemoPD; however, transcriptomic analysis revealed the enrichment of metabolic pathways, including arginine metabolism, in ChemoPD tumors. These findings were supported by metabolomics data from preclinical models. …
Fibulin-4 Expressed In Metastatic Breast Cancer Is A Target Of Peptide-Based Imaging Probes And Experimental Therapeutics, Alexes C Daquinag, Sukhen C Ghosh, Solmaz Aghaamiri, Stephen M Farmer, Sheng Zhang, Servando Hernandez Vargas, Ashwin K Ramesh, Zhiqiang An, Ali Azhdarinia, Mikhail G Kolonin
Fibulin-4 Expressed In Metastatic Breast Cancer Is A Target Of Peptide-Based Imaging Probes And Experimental Therapeutics, Alexes C Daquinag, Sukhen C Ghosh, Solmaz Aghaamiri, Stephen M Farmer, Sheng Zhang, Servando Hernandez Vargas, Ashwin K Ramesh, Zhiqiang An, Ali Azhdarinia, Mikhail G Kolonin
The Brown Foundation: Institute of Molecular Medicine
There is a lack of approaches to detect and kill metastatic cells. As an agent for metastasis targeting, a cyclic peptide BLMP6 has been previously characterized. As a step toward translation, we designed AZDye555-labeled BLMP6 and demonstrated its homing to metastases of human MDA-MB-231 cells in mice. We show that 68Ga-radiolabeled BLMP6 can be used for the detection of MDA-MB-231 metastases. We designed a peptide-drug conjugate consisting of monomethyl auristatin E (MMAE) and BLMP6. We show that MMAE-BLMP6 kills MDA-MB-231 cells in cell culture and in vivo. In mouse models of lung metastases, treatment with MMAE-BLMP6 suppressed metastasis growth …
Macrophages As Gatekeepers Of Glioma Progression, Cliona M Rooney, Jasia Mahdi
Macrophages As Gatekeepers Of Glioma Progression, Cliona M Rooney, Jasia Mahdi
Faculty, Staff and Students Publications
No abstract provided.
The Association Of Daily Urinary And Bowel Incontinence With Emotional Functioning In Young Adults With Spina Bifida: An Ecological Momentary Assessment Study, Audrey I. Young '26, Devon J. Hensel, Konrad M. Szymanki
The Association Of Daily Urinary And Bowel Incontinence With Emotional Functioning In Young Adults With Spina Bifida: An Ecological Momentary Assessment Study, Audrey I. Young '26, Devon J. Hensel, Konrad M. Szymanki
Student Research
Many young adults with spina bifida experience bladder and bowel leakage, but clinic visits often rely on people remembering and summarizing their symptoms over long periods. In this study, we asked participants to report their experiences each day for one month using simple phone-based check-ins. We found that leakage does not affect every day in the same way. On days when symptoms were more frequent or harder to manage, participants reported worse mood, more worry, and were more likely to avoid activities. These day-to-day experiences also related to over- all quality of life at the end of the month. For …
Placenta Accreta Spectrum Risk In Endometriosis: A Retrospective Cohort Study With Art Subanalysis, Madeline West, Amir Alsaidi, Michael A Belfort, Hendrik A Lombaard, Yamely H Mendez, Christina C Reed, Amir A Shamshirsaz, Jessian L Munoz
Placenta Accreta Spectrum Risk In Endometriosis: A Retrospective Cohort Study With Art Subanalysis, Madeline West, Amir Alsaidi, Michael A Belfort, Hendrik A Lombaard, Yamely H Mendez, Christina C Reed, Amir A Shamshirsaz, Jessian L Munoz
Faculty, Staff and Students Publications
No abstract provided.
Detection, Persistence, And Rising Prevalence Of Oncogenic Viruses Revealed By Wastewater Metagenomics, Harihara Prakash, Ryan K Perez, Matt Ross, Michael Tisza, Sara J Javornik Cregeen, Jennifer Deegan, Joseph F Petrosino, Eric Boerwinkle, Justin R Clark, Anthony W Maresso
Detection, Persistence, And Rising Prevalence Of Oncogenic Viruses Revealed By Wastewater Metagenomics, Harihara Prakash, Ryan K Perez, Matt Ross, Michael Tisza, Sara J Javornik Cregeen, Jennifer Deegan, Joseph F Petrosino, Eric Boerwinkle, Justin R Clark, Anthony W Maresso
Faculty, Staff and Students Publications
Oncogenic viruses cause high-risk cancers in humans and are responsible for nearly 20% of all cancer cases worldwide. Currently, very limited data exist in the realm of wastewater-based viral epidemiology (WBE) for cancer-causing viruses, with existing studies using targeted approaches (i.e., PCR-based approaches) that lack genomic resolution. In this study, we used a hybrid-capture approach to detect, filter, and sequence all known oncogenic virus signals from wastewater samples collected over 3 years (May 2022-May 2025) in 16 Texas cities, covering nearly 25% of the state's population. Once sequenced, we used custom computational tools designed for wastewater metagenomics to assign reads …
Management Algorithm For Vasoplegic Shock After Cardiac Surgery: An Interdisciplinary Collaboration, Subhasis Chatterjee, Jamel Ortoleva, Rakesh C Arora, Kelci R Dalton, Daniel T Engelman, Natalia Ivascu Girardi, Michael C Grant, Travis J Miles, Marc R Moon, Orlando R Suero, Erica Wittwer, Patrick M Wieruszewski
Management Algorithm For Vasoplegic Shock After Cardiac Surgery: An Interdisciplinary Collaboration, Subhasis Chatterjee, Jamel Ortoleva, Rakesh C Arora, Kelci R Dalton, Daniel T Engelman, Natalia Ivascu Girardi, Michael C Grant, Travis J Miles, Marc R Moon, Orlando R Suero, Erica Wittwer, Patrick M Wieruszewski
Faculty, Staff and Students Publications
Background: Vasoplegic shock is distributive shock that follows cardiopulmonary bypass, characterized by hypotension, low systemic vascular resistance, and catecholamine resistance despite preserved or elevated cardiac output. Reported incidence ranges from 5% to 50%. Associated adverse outcomes include acute kidney injury, prolonged intensive care unit stay, and mortality. A single, universally accepted consensus definition is lacking, and few evidence-based best-practice management strategies exist.
Methods: A panel of 12 clinicians-cardiac surgeons, anesthesiologists, intensivists, and pharmacists-from 6 institutions conducted a structured expert review. PubMed and Embase were searched for research studies, including clinical trials, retrospective analyses, and mechanistic studies covering epidemiology, risk factors, …
Comprehensive Geriatric Assessment Identifies Multidimensional Vulnerabilities In Older Adults With Heart Failure, Ci̇han Kiliç, Rengi̇n Demi̇r, Özlem Yilmaz Aykent, Zerri̇n Yi̇ği̇t, Pinar Küçükdağli, Banu Özulu Türkmen, Güli̇stan Bahat, Mehmet Aki̇f Karan
Comprehensive Geriatric Assessment Identifies Multidimensional Vulnerabilities In Older Adults With Heart Failure, Ci̇han Kiliç, Rengi̇n Demi̇r, Özlem Yilmaz Aykent, Zerri̇n Yi̇ği̇t, Pinar Küçükdağli, Banu Özulu Türkmen, Güli̇stan Bahat, Mehmet Aki̇f Karan
Turkish Journal of Medical Sciences
Background/aim: Heart failure (HF) in older adults is frequently accompanied by geriatric syndromes that remain unrecognized in conventional cardiac evaluations. The vulnerabilities of older adults with and without HF in terms of muscle strength, physical performance, functional capacity, frailty, nutritional status, cognition, mood, anxiety, polypharmacy, and comorbidity were investigated using comprehensive geriatric assessment (CGA).
Materials and methods: A cross-sectional study was conducted in two academic outpatient clinics, enrolling 420 adults aged ≥60 years, including 92 (21.9%) with HF. Data included sociodemographic characteristics, anthropometric measurements, and CGA parameters: handgrip strength, the Five-Times Sit-to-Stand Test (FTSST), the Short Physical Performance Battery (SPPB), …
Bridging The Methodological Gap In Multitrauma Literature: A Competency-Based Educational Framework And Clinical Appraisal Filter, Şaki̇r Hakan Aksu, Burcu Doğan, Merve Yazla
Bridging The Methodological Gap In Multitrauma Literature: A Competency-Based Educational Framework And Clinical Appraisal Filter, Şaki̇r Hakan Aksu, Burcu Doğan, Merve Yazla
Turkish Journal of Medical Sciences
Background/aim: The statistical complexity of contemporary multitrauma literature has increased considerably in recent years, which may pose challenges for clinicians seeking to interpret high-impact research and apply evidence-based practices. Characterizing this methodological landscape and exploring education-oriented approaches may help to improve the interpretability of the literature and support informed clinical decision-making.
Materials and methods: A cross-sectional analysis was conducted on the 100 most-cited multitrauma studies published in Science Citation Index Expanded journals indexed in the Web of Science database between January 2018 and November 2025. The statistical methods used in each article were categorized into the three competency levels of …
Optimistic And Ambivalent Attitudes Toward Clinical Artificial Intelligence, Sevi̇l Uygun İli̇khan, Si̇nem Ülke, Mahmut Özer, Matjaž Perc, Yavuz Ayhan
Optimistic And Ambivalent Attitudes Toward Clinical Artificial Intelligence, Sevi̇l Uygun İli̇khan, Si̇nem Ülke, Mahmut Özer, Matjaž Perc, Yavuz Ayhan
Turkish Journal of Medical Sciences
Background/aim: Artificial intelligence (AI) is increasingly being integrated into healthcare systems; however, healthcare professionals’ knowledge, attitudes, and perceptions regarding AI remain insufficiently understood. This study aimed to evaluate healthcare professionals’ perceptions of AI in clinical practice.
Materials and methods: This descriptive cross-sectional study included 260 healthcare professionals, including physicians, nurses, and healthcare technicians working at a tertiary public hospital in Türkiye. Participants completed the Healthcare Professionals and Artificial Intelligence Questionnaire, which assessed demographic characteristics, AI knowledge, workplace AI use, attitudes toward AI applications, ethical and legal concerns, perceived professional impact, and educational needs.
Results: Most participants reported limited AI knowledge; …
Reliability And Validity Of The Turkish Version Of The Barthel Index-Dyspnea In Patients With Pulmonary Hypertension, Pinar Merç, Rengi̇n Demi̇r, Meli̇h Zeren, Habi̇be Durdu, Ümi̇t Yaşar Si̇nan, Mehmet Serdar Küçükoğlu
Reliability And Validity Of The Turkish Version Of The Barthel Index-Dyspnea In Patients With Pulmonary Hypertension, Pinar Merç, Rengi̇n Demi̇r, Meli̇h Zeren, Habi̇be Durdu, Ümi̇t Yaşar Si̇nan, Mehmet Serdar Küçükoğlu
Turkish Journal of Medical Sciences
Background/aim: The Barthel Index-dyspnea (BI-d) is a respiratory disease-specific tool developed on the basis of the Barthel Index (BI), which provides a simple and quick way to measure the degree of dyspnea in activities of daily living (ADL). Dyspnea is one of the most common symptoms of pulmonary hypertension (PH). The objective of this study was to explore the reliability and validity of the Turkish version of the BI-d in patients with PH.
Materials and methods: A total of 73 PH patients were included in the study. Criterion validity was explored using the modified Medical Research Council (mMRC) dyspnea scale, …