Medicine and Health Sciences Commons^™

A Systematic Comparative Review Of Antipsychotic Efficacy And Safety In The Treatment Of Hiccups, Omar Alshargi, Samah Alzaid, Zainab Albahouth, Muradi Hassan Albanji, Hala Makki, Rawan. F. Alboqami, Maram Al Shammari, Huda Alruwaili, Fawaz Alruwaili, Rahmah Ali Algarni, Omar Ibrahim Albahouth

Neurosciences

Objective: To evaluate and compare the safety and effectiveness of antipsychotic medications for the treatment of hiccups, thereby guiding clinicians toward evidence-based treatment guidelines. Hiccups are often benign and self-limiting; however, they can become persistent and intractable, adversely affecting the quality of life. Antipsychotics have been identified as a therapeutic option for the management of hiccups; however, the available evidence supporting their safety and efficacy has not been synthesized.

Methods: This review utilized the revised Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Cochrane Risk of Bias Assessment Tool was modified to evaluate the quality of the …

Subliminal Priming Effects On Motor And Cognitive Performance: Pilot Evidence With Implications For Neurorehabilitation, Rehab E Aljuhni, Ghader A Alqadhi, Saud A Alhassan, Sultan A Alanazi

Neurosciences

Objective: To investigate whether subliminal priming modalities (visual, auditory, or word-based) influence motor and cognitive performance in healthy young adults, and whether these effects vary by gender.

Methods: A total of 30 healthy adults were assigned to visual, auditory, or word-based priming using single-blind, stratified randomization. Subliminal stimuli were presented for 50 ms. Motor outcomes included reaction time on dominant (RT-R) and non-dominant (RT-L) sides, comfortable and maximal walking speeds measured by the 10-Meter Walk Test (10MWT), and functional mobility assessed using the Timed Up and Go (TUG) test. Cognitive performance assessed using the Trail Making Test (TMT). Outcomes were …

Sub-Regional Motor–Somatosensory Connectivity And Lifespan Plasticity In Functional Networks, Adnan A. S. Alahmadi

Neurosciences

Objectives: To determine how cytoarchitectonically defined subdivisions of the primary motor cortex, somatosensory cortex, and supplementary motor area (SMA) reorganize their integration with large-scale brain networks during healthy aging. This study investigated the lifespan trajectories of functional connectivity within cytoarchitectonically defined subregions of the primary motor cortex, somatosensory cortex, and supplementary motor area (SMA).

Methods: We conducted a cross-sectional analysis of resting-state fMRI data from 150 healthy individuals (aged 23–80 years), stratified into young, middle-aged, and older groups. Data were sourced from the Southwest University Adult Lifespan Dataset (SALD) and analyzed between June 2024 and June 2025. Using the Jülich …

Relationships Between The Corpus Callosum Index And Current Blood Parameters And Temporal Changes In These Parameters In Patients With Multiple Sclerosis, Oruç Şahin, Muzaffer Güneş

Neurosciences

Objectives: This study aimed to investigate changes in blood parameters and examine the relationships among the corpus callosum index (CCI), plaque characteristics, and blood parameters in multiple sclerosis (MS) patients. In MS, the CCI is associated with brain atrophy and disease progression.

Methods: In this retrospective, cross-sectional study, demographic data from 103 MS patients (38 males), along with blood parameters obtained five years earlier and current values, were analyzed in relation to magnetic resonance imaging (MRI) findings. The CCI calculated from MRI scans was assessed in relation to plaque distribution and number. Statistical analyses included paired sample t tests, Wilcoxon …

Clinical Characteristics Of Multiple Sclerosis And Association Of Ms Severity With Vitamin D Level In The Madinah Region Of Saudi Arabia: A Cross-Sectional Study, Majed M. Alluqmani

Neurosciences

Objective: To determine the prevalence of multiple sclerosis (MS) in the western region of Saudi Arabia and correlate it with its predictors among a cohort of patients. The prevalence of MS is increasing in Saudi Arabia, and is attributed to various factors such as recent lifestyle changes, improved disease recognition, and parental consanguinity. Knowing the exact prevalence of the disease may enhance disease management.

Methods: This cross-sectional study was conducted among individuals diagnosed with MS at clinics in the Madinah region.

Results: The study found that the prevalence of multiple sclerosis is lower in the Madinah region. Additionally, …

The Top 50 Cited Articles In Pediatric Neurology: A Bibliometric Analysis, Anas Alyazidi, Osama Muthaffar, Ahmed Bamaga, Hebah Qashqari, Abdulmalek Alhithlool, Ahmad Alanezi, Sameer Almehmadi, Mohamed Babiker, Fahad Bashiri

Neurosciences

Objectives: To identify and analyze the most influential articles within the field of pediatric neurology through a bibliometric lens. As pediatric neurology continues to expand across subspecialties, identifying landmark studies is critical for understanding clinical and research priorities. Bibliometric analysis enables the evaluation of citation trends to highlight impactful contributions that have shaped the field.

Method: A bibliometric analysis of the 50 most-cited pediatric neurology articles was conducted. Articles were assessed by citation metrics, study design, subspecialty, journal impact factor (JIF), and funding status. Correlation and regression analyses evaluated associations between variables.

Results: Citation counts ranged from 185 to 1,440 …

Prevalence Of Depression Among Patients With Epilepsy In Saudi Arabia: A Nationwide Systematic Review And Meta-Analysis, Mothana Y. Al Jabr, Aryam M. Alenizi, Faisal S. Aleisa, Mazen A. Alghamdi, Noura I. Alfehaid, Muteb M. Alqahtani, Abbas S. Almutair

Neurosciences

Objective: To assess the pooled prevalence of depression among epilepsy patients and find the associated demographics and psychosocial factors. Mood disorders are significant comorbidity between patients diagnosed with epilepsy, adversely influencing quality of life and complicating disease management. However, the incidence, prevalence, and associated risk factors of depression in patients diagnosed with epilepsy in Saudi Arabia are not well elucidated.

Methods: This review was employed used studies retrieved from medical databases and the Saudi Digital Library. Observational and cross-sectional studies assessing depression between patients diagnosed with epilepsy in Saudi Arabia were included. Data were analyzed using the Freeman–Tukey double arcsine …

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 …

Fatigue And Depression In Epilepsy Patients May Not Be Solely Related To The Epilepsy Itself, Sounira Mehri, Josef Finsterer

Neurosciences

No abstract provided.

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

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 ± …

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 …

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

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 …

Mutation Screening For Confirming Suspected Spinal Muscular Atrophy Using Dried Blood Spotted On In-House Cellulose-Based Cards, Yogik Onky Silvana Wijaya, Farda Tsaqouva Ahza, Annisa Naufal Almaszahra, Mawaddah Ar Rochmah, Dian Kesumapramudya Nurputra

Makara Journal of Science

Early and accurate diagnosis for spinal muscular atrophy (SMA) has gained relevance in an era of emerging therapies to improve patient outcomes. While screening of dried blood spots (DBS) effectively detects deletion-type SMA, non-deletion cases are often missed. Mutation screening from DBS is needed to address this gap. Here, we aimed to evaluate the feasibility of an in-house, cellulose-based card for direct Sanger sequencing for variant hunting, avoiding DNA extraction and offering an alternative to commercial cards. As a proof of concept, sequences obtained from DBSs of 23 healthy individuals were compared with sequences derived from isolated genomic DNA (gDNA). …

Impact Of Anatomical Changes On Treatment Plan Robustness: A Comparative Study Of Intensity Modulated Proton Therapy And Volumetric Modulated Arc Therapy In Head And Neck Cancer., Jennifer Croft

Masters Projects

Head and neck cancer patients often experience anatomical changes during radiation therapy, including weight loss and tumor regression. These changes can alter planned dose distribution and affect treatment accuracy. Based on the previous understanding, IMPT offers highly conformal dose delivery but is sensitive to the patient’s geometry changes and daily setup uncertainties, while VMAT may provide greater stability under these uncertainties. However, as of today, there is no quantitative analysis and comparison between the two modalities using real clinical data. The purpose of this study is to compare the robustness of IMPT and VMAT for head and neck cancer by …

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 …

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 …

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 …

Intouch Week Of June 22, 2026, New York Medical College

InTouch

• Sixth Annual NYMC Golf Tournament Drives Support for Future Health Care Leaders
• Center for Disaster Medicine Receives NYS Funding
• Dean’s Faculty Awards Recognize Excellence in Teaching, Mentoring, and Service
• Football Associated with Nearly One in Five Brain Injuries in Youth Sports
• Touro College of Dental Medicine Hosts Its Ninth Annual Golf, Tennis and Mahjong Event
• Alumni Spotlight: Sumaita Mahmood, M.D./M.P.H. ’26, Receives National Public Health Award

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

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

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 …

Sirt1 And Ifi16 Cooperatively Regulate Hbv Replication Via Epigenetic Modulation And Innate Immune Activation, Zahra Zahid Piracha, Umar Saeed, Neelam Abid, Syed Shahan Gilani, Hafiz Ahmad Bilal Akhtar Chughtai, Areesha Wasti, Muhammad Waseem, Dilber Uzun Ozsahin, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Background

Hepatitis B virus (HBV) establishes persistent infection through the formation of a covalently closed circular DNA (cccDNA) minichromosome, which enables immune evasion and sustained viral replication. While SIRT1, IFI16, and STING are known to modulate antiviral pathways, their cooperative role in regulating HBV transcription and host immunity remains poorly defined.

Methods

We investigated the functional interplay between SIRT1, IFI16, and STING using confocal microscopy, chromatin immunoprecipitation (ChIP), gene silencing, and quantitative PCR in HBV-replicating cell models. Interactions with HBV cccDNA and effects on viral transcription and interferon-stimulated gene (ISG) expression were analyzed. Northern blotting and RT-qPCR were used to …

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 …

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 …

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. …

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 …

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 …

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, …