Digital Commons Network^™

Protocol For Isolation Of Lipid Droplets And Mitochondria From Acute Myeloid Leukemia Cells For Lipidomic Analysis, Ran Zhao, Liang Zhang, Shuxin Dong, Kazuharu Kamachi, Saurabh Kumar Gupta, Hiroki Akiyama, Jalen Nguyen, G Lavender Hackman, Michael Andreeff, Alessia Lodi, Jo Ishizawa

Faculty, Staff and Student Publications

Lipid droplets (LDs) are dynamic organelles critical for lipid and energy homeostasis. LD dysregulation is implicated in various diseases, including acute myeloid leukemia (AML), which exhibits aberrant lipid metabolism and chemoresistance. Here, we describe an effective protocol for the co-isolation of LDs and mitochondria from lipid-deficient cell types, e.g., AML cells. We detail procedures for the isolation, quality verification, and results from mass spectrometry-based lipidomic analysis. This protocol enables the functional study of organellar lipidomic regulation in AML.

Acute And Chronic Effects Of Neuroinflammation On Hippocampus And Anterior Cingulate Cortex Network Dynamics, Lauren A. Crew

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neuroinflammation has emerged as a critical modulator of cognitive function and neural circuit dynamics, yet the distinct contributions of acute and chronic neuroinflammation to brain function remain poorly defined. This dissertation examines how inflammation independently alters large-scale neural activity and behavior, focusing on interactions between the hippocampus (HPC) and anterior cingulate cortex (ACC), regions essential for memory and executive processes. Using in vivo electrophysiological techniques in a rodent model, this study compares the effects of short-term (acute) and prolonged (chronic) neuroinflammatory states, induced via Poly I:C, on neural oscillations, regional coherence, and spatial coding. Findings reveal that even transient inflammation …

Mitochondrial Complex Ii Orchestrates Divergent Effects In Cd4+ And Cd8+ T Cells, Keisuke Seike, Shih-Chun A Chu, Yuichi Sumii, Takashi Ikeda, Meng-Chih Wu, Laure Maneix, Dongchang Zhao, Yaping Sun, Marcin Cieslik, Pavan Reddy

Faculty, Staff and Students Publications

Mitochondrial metabolism orchestrates T cell functions, yet the role of specific mitochondrial components in distinct T cell subsets remains poorly understood. Here, we explored the role of mitochondrial complex II (MC II), the only complex from the electron transport chain (ETC) that plays a role in both ETC and metabolism, in regulating T cell functions. Surprisingly, MC II exerts divergent effects on CD4+ and CD8+ T cell activation and function. Using T cell-specific MC II subunit, succinate dehydrogenase A-deficient (SDHA-deficient) mice, we integrated single-cell RNA-seq and metabolic profiling, with in vitro and in vivo T cell functional assays to illuminate …

Facts And Hopes Of Chimeric Antigen Receptor-Redirected Nk T Cells, Amy N Courtney, Xin Zhou, Gengwen Tian, Ying Wang, Leonid S Metelitsa, Gianpietro Dotti

Faculty, Staff and Students Publications

Chimeric antigen receptor (CAR)-engineered invariant NK T cells (CAR-NKT) are a novel cell platform for cancer immunotherapy. Unlike conventional T cells, NKTs are characterized by innate antitumor properties, minimal alloreactivity, and a unique ability to modulate the tumor microenvironment. This article provides a comprehensive overview of preclinical and early clinical studies evaluating CAR-NKTs in both autologous and allogeneic clinical settings. We discuss the contributions of CAR signaling domains, cytokine coexpression, and other functional measures that correlate with CAR-NKT persistence, function, and metabolic fitness. We also discuss the critical role of immunocompetent animal models in elucidating the interactions of CAR-NKTs with …

A Long Non-Coding Rna Leat1 Mediates The Hormone Responsiveness Of Efnb2 During Male Urogenital Development, Deidre Mattiske, Pascal Bernard, Paul E Gradie, Richard R Behringer, Paul A Overbeek, Rachel J O'Neill, Tiffany Phillips, Melanie Stewart, Neil Youngson, Gerard Tarulli, Andrew J Pask

Faculty, Staff and Students Publications

The novel long non-coding RNA (lncRNA) Leat1 is extraordinarily conserved in both its location (syntenic with EfnB2, an essential gene in anogenital patterning) and sequence. Here we show that Leat1 is upregulated following the production of testosterone from the developing testis in mice and interacts with EfnB2, positively regulating its expression. Leat1 expression is suppressed by estrogen, which in turn suppresses the expression of EfnB2. Moreover, the loss of Leat1 leads to reduced EfnB2, resulting in a severe hypospadias phenotype. The human LEAT1 gene is also co-expressed with EFNB2 in the developing human penis, suggesting a conserved function for this …

Transdiagnostic Links Of Reward Processing In Obsessive-Compulsive Disorder And Depression, Kevin M Wagner, Matti Cervin, Jessica S C Cheng, Jasmine Arriaga, Vanessa Zavala Cruz, Dayan Berrones, Josselyn S Muñoz, Renee M Frederick, Jacey L Anderberg, Belinda E Núñez Bracho, Victor R Adorno, Leonardo F Fontenelle, Andrew D Wiese, Latin American Trans-Ancestry Initiative For Ocd Genomics (Latino), Brazilian Obsessive-Compulsive Spectrum Disorder Working Group (Gttoc), James J Crowley, Eric A Storch

Faculty, Staff and Students Publications

Objectives: Transdiagnostic models aim to uncover shared mechanisms across mental disorders. Reward responsiveness (the ability to experience pleasure from rewarding stimuli) is a plausible, yet underexplored, transdiagnostic mechanism linking obsessive-compulsive disorder (OCD) and depression. This study used network analysis to (1) examine how key reward responsiveness domains are interlinked in individuals with OCD and (2) explore how each domain is uniquely associated with OCD and depression.

Methods: A total of 1345 individuals with a history of OCD symptoms (ages 18-88, 71 % women) from Latino communities in the United States (including Puerto Rico) and nine Latin American countries completed validated …

Patient-Derived Ovarian Cancer Models Provide Insight Into Cancer Cell-Intrinsic And Immune Cell-Dependent Effects On Therapeutic Response, Parisa Nikeghbal

Biomedical Sciences ETDs

Ovarian cancer is the most lethal gynecologic malignancy, largely due to late diagnosis and resistance to chemotherapy. This dissertation applies patient-derived organoids (PDOs), xenograft-derived organoids (PDXOs), and humanized xenografts (huPDX) to investigate therapeutic responses and immune interactions. Organoids were shown to retain critical features of the original malignancy. Across platinum-sensitive, -resistant, and -refractory cases, both PDOs and PDXOs exhibited drug sensitivities that aligned with patients’ clinical classifications. Building on this foundation, a drug screen revealed novel strategies. Auranofin restored platinum sensitivity in Notch3-active models, afatinib broadly reduced viability, and adavosertib–gemcitabine and sorafenib–topotecan combinations produced synergy. Extending this work, immune interactions …

Dermal Lymphatic Carcinomatosis As A Cutaneous Metastasis From Epidermal Growth Factor Receptor-Positive Lung Adenocarcinoma: A Case Report, Sarah A. Hemelt, Jonathan M. Joseph, Nicholas Culotta

School of Medicine Faculty Publications

Cutaneous metastases are an uncommon but clinically significant manifestation of internal malignancies. We present a rare case of dermal lymphatic carcinomatosis arising from epidermal growth factor receptor (EGFR)-positive lung adenocarcinoma, a presentation that may closely mimic inflammatory dermatoses and indicate therapeutic resistance or disease progression. We describe the clinical course of a 65-year-old woman who developed a violaceous cutaneous metastatic lesion beneath the left breast during treatment for metastatic lung adenocarcinoma. This case highlights the importance of recognizing cutaneous signs as indicators of disease progression and emphasizes the diagnostic challenges and prognostic implications of cutaneous metastases in lung cancer.

The Pathophysiological Role Of Mitochondrial Acid-Sensing Ion Channel 1a In Hypoxic Pulmonary Hypertension, Megan N. Tuineau

Biomedical Sciences ETDs

Pulmonary hypertension (PH) is characterized by increased pulmonary arterial constriction, pulmonary arterial remodeling, and right ventricular dysfunction. While metabolic and mitochondrial derangements are increasingly recognized as central pathogenic features, the underlying mechanisms and effectors are not yet fully understood. Acid-sensing ion channel 1a (ASIC1a) is a proton-gated cation channel involved in the development of chronic hypoxia (CH)-induced PH. ASIC1a represents a potential candidate involved in metabolic-mitochondrial dysfunction, as metabolic byproducts can act as ligands for ASIC1a. Additionally, ASIC1a has recently been identified as a mitochondrial ion channel involved in neuronal death following oxidative stress. Therefore, we hypothesize that ASIC1a functions …

Krasg12d Mutation Promotes Pancreatic Tumorigenesis By Suppressing Sirtuin Three Via The Guanine Nucleotide Exchange Factor Rcc1, Taoyi Mai, Mengwen Wang, Ya Qiu, Wenhua Lu, Hongyu Wu, Shuna Chen, Paul J Chiao, Peng Huang

Faculty, Staff and Student Publications

KRASG12D mutation is a prevalent gain-of-function mutation that drives pancreatic cancer tumorigenesis, but the underlying mechanisms that promote KRAS-induced cell proliferation and tumor formation remain elusive. To uncover the molecular pathways that facilitate KRASG12D-driven malignant transformation, we measured the transcriptomic alterations at various time points after induction of KRASG12D expression in human pancreatic normal epithelial cells. KEGG pathway enrichment of the differentially expressed genes (DEGs) showed that the major DEGs were located in pathways that regulate nicotinate/nicotinamide metabolism, TNF signaling, and microRNAs associated with cancer. Among these molecular alterations, the NAD-dependent deacetylase gene SIRT3 was significantly down-regulated by KRASG12D. Conversely, …

In Recent Research: Exosomal And Molecular Regulators Of Browning And Thermogenesis In Adipose Tissues, Merve İnel, Bahadir Öztürk

Turkish Journal of Medical Sciences

This review synthesizes current knowledge on the molecular mechanisms regulating brown, white, and beige adipose tissues, with particular emphasis on the browning process of white adipose tissue. Rather than considering adipose tissue as a passive energy reservoir, this review underscores its active role as a dynamic endocrine and metabolic organ. Brown and beige adipose tissues, recognized for their thermogenic capacity and contribution to energy expenditure, have emerged as promising therapeutic targets for the treatment of obesity, type 2 diabetes, and related metabolic disorders. The review draws upon recent findings on adrenergic signaling, transcription factors, exosomal microRNAs, and other novel regulatory …

Relcovaptan: A Promising Therapeutic Agent In Traumatic Spinal Cord Injury That Acts By Modulating Newly Identified Transcriptional Regulators Of Aquaporins Compared To Tolvaptan, Şeyma İş, Duygu Ceman, Meri̇h İş, Neşe Keser, Şaban Teki̇n

Turkish Journal of Medical Sciences

Background/aim: Every year, hundreds of thousands of people worldwide suffer from traumatic spinal cord injury (tSCI), which causes irreversible damage, edema, and inflammation. Despite its devastating impact, no safe and effective medication is available. Edema formation is one of the earliest pathological events in tSCI, beginning within minutes after injury. Cytotoxic edema progresses to vasogenic edema, exacerbating irreversible damage. Our study aimed to investigate a therapeutic approach targeting cytotoxic edema in the acute phase of tSCI to improve treatment outcomes. Aquaporins (AQPs) are crucial in edema formation and tSCI pathogenesis. Vasopressin, also known as the antidiuretic hormone, modulates Aqp expression …

Transformation Of Juvenile Idiopathic Arthritis In Adult-Oriented Rheumatology Care, Şeri̇fe Asya Germe Dağlioğlu, Zeynep Balik, Zehra Özsoy, Yunus Emre Dalkiliç, Ezgi̇ Deni̇z Batu, Özge Başaran, Yelda Bi̇lgi̇ner, Umut Kalyoncu, Seza Özen, Şule Apraş Bi̇lgen, Levent Kiliç

Turkish Journal of Medical Sciences

Background/aim: Juvenile idiopathic arthritis (JIA) is the most prevalent form of chronic inflammatory arthritis in children, and the symptoms persist into adulthood for a considerable number of patients. This study aimed to compare the JIA subtypes using the diagnostic criteria used for adults and identify the clinical characteristics and treatment approaches for patients with JIA transitioning to adult-oriented rheumatology care.

Materials and methods: Patients diagnosed with JIA in the pediatric rheumatology clinic were retrospectively evaluated. The patients (n=107) who had at least one follow-up visit in the adult rheumatology clinic were included in the study. After transitioning from pediatric to …

Evaluation Of Prognostic Value Of Vascular Endothelial Growth Factor And Endocan In Non-Small Cell Lung Cancer, Mesut Meli̇h Özercan, Burcu Ancin, Yi̇ği̇t Yilmaz, Ahmet Müderri̇soğlu, Serkan Uysal, Ulaş Kumbasar, Zeynep Saribaş, Erkan Di̇kmen, Riza Doğan

Turkish Journal of Medical Sciences

Background/aim: No reliable, easily measurable biomarker currently exists for the screening or prognosis of lung cancer. The present study evaluates the potential utility of vascular endothelial growth factor (VEGF) and endocan, which can be readily measured in blood samples, as biomarkers for screening and prognostic assessment in lung cancer.

Materials and methods: Included in the study were 38 patients with early-stage non-small cell lung cancer (NSCLC) and 29 controls. All patients underwent surgical intervention and were monitored for 1 month postoperatively. Serum VEGF and endocan levels were measured preoperatively and postoperatively. Clinical characteristics, laboratory data, and histopathological findings were recorded …

Diagnostic Yield Of Clinical Exome Sequencing In Patients With Suspected Hereditary Neuropathy, Can Ebru Beki̇rcan-Kurt, Doruk Arslan, Naz Güleray, Sevi̇m Erdem-Özdamar, Burcu Balci-Hayta, Ersi̇n Tan

Turkish Journal of Medical Sciences

Background/aim: Hereditary neuropathies exhibit significant genetic heterogeneities, often making molecular diagnosis challenging. Clinical Exome Sequencing (CES) allows the simultaneous evaluation of a wide range of candidate genes, and can be considered an efficient approach to identifying underlying genetic causes. The present study assesses the diagnostic utility of CES in patients with clinically suspected hereditary neuropathy.

Materials and methods: Included in the study were 21 patients with clinically suspected hereditary neuropathy who underwent CES. DNA samples were isolated from peripheral blood and subjected to CES on an Illumina NextSeq 2000 system, while a bioinformatics analysis and variant interpretation were performed using …

Comparison Of Spatiotemporal And Arm Swing Characteristics Of Gait Between Patients With Copd And Healthy Controls, Hi̇daye Yamikan, Ni̇hat Özgören, Serdar Aritan, Oğuz Karcioğlu, Aynur Demi̇rel

Turkish Journal of Medical Sciences

Background/aim: Impairments in spatiotemporal gait characteristics have been observed in patients with chronic obstructive pulmonary disease (COPD). However, arm swing characteristics—a fundamental component of gait that play a key role in maintaining gait stability and energy efficiency—have been largely overlooked. This study aimed to investigate the spatiotemporal characteristics of gait, together with arm swing patterns, in patients with COPD.

Materials and methods: A total of 20 patients with COPD (aged 40–65 years) and 20 age- and sex-matched healthy controls (HC) participated in this cross-sectional study. Spatiotemporal gait characteristics and arm swing data were recorded using a motion capture system equipped …

Exploring Gender Differences In The Impact Of Sleep And Fatigue On Disease Severity In Rheumatoid Arthritis: A Moderated Mediation Model, Musa Salmanoğlu, Habi̇p Yilmaz

Turkish Journal of Medical Sciences

Background/aim: Rheumatoid arthritis (RA) is often accompanied by fatigue and sleep disturbances, which aggravate disease severity. Gender differences in these interrelationships remain insufficiently understood. This study aimed to examine whether fatigue mediates the association between sleep quality and disease severity in RA, and whether these pathways differ by gender.

Materials and methods: A single-center study was conducted with 68 RA patients (55.9% female). Disease severity was assessed using the Routine Assessment of Patient Index Data-3, fatigue using the Bristol Rheumatology Fatigue Multidimensional Questionnaire, and sleep quality using the Pittsburgh Sleep Quality Index (PSQI).

Results: Fatigue significantly mediated the relationship between …

Moltkia Coerulea Extracts Alleviate Caspase-3 Activity Via Reducing Oxidative Stress In Lps-Induced Neurotoxicity In Bv-2 Cells, Asli Can Ağca, Derya Altay, Hüdaverdi̇ Kul, Asli F. Ceylan, Betül Sever Yilmaz

Turkish Journal of Medical Sciences

Background/aim: Moltkia coerulea, a medicinal plant traditionally used for its neuroprotective properties, contains diverse phenolic compounds. However, its mechanisms of action in neuroinflammation remain unclear. We hypothesized that extracts of M. coerulea may protect microglial cells from lipopolysaccharide (LPS)-induced oxidative stress and apoptosis by modulating reactive oxygen species (ROS) and caspase-3 activity.

Materials and methods: Aqueous and methanol extracts (5–50 μg/mL) were tested in BV-2 microglial cells. Cell viability was assessed by MTT assay, while ROS generation and caspase-3 activity were measured using fluorescence-based kits. The effective concentration (10 μg/mL) was selected for mechanistic assays based on viability data and …

Clinical Characteristics Of Graves’ Disease Following Covid-19 Infection Or Vaccination: A Multicenter Case-Control Study, Asena Gökçay Canpolat, Kemal Ağbaht, Ati̇lla Hali̇l Elhan, Mustafa Cesur, Zi̇ynet Alphan Uç, Seçki̇n Akçay, Hülya Iliksu Gözü, Mehmet Aşik, Hayri̇ Bostan, Beki̇r Ucan, Tugçe Şah Ünal, Merve Yilmaz, Ayşe Kubat Üzüm, Mehmet Çağri Ünal, Cuneyd Anil, Ümmü Mutlu, Nurcan İnce, Sevgül Faki, Güven Bari̇s Cansu, Mehmet Sercan Erturk, Ayten Oguz, Mustafa Aydemi̇r, Şefi̇ka Burçak Polat, Oya Topaloğlu, Reyhan Ersoy, Beki̇r Çakir, Ayşe Ok, Ersen Karakiliç, Muhi̇tti̇n Yalçin, Yusuf Kayhan, Kader Ugur, Di̇lek Yazici, Alper Gürlek, Tülay Omma, Emre Serdar Saygili, Adnan Batman, Banu Kara, Göknur Yorulmaz, Bahri Evren, Füsun Baloş Törüner, Bülent Okan Yildiz, Murat Erdogan Fai̇k, Faruk Alagol, Erman Çakal, Mustafa Şahi̇n

Turkish Journal of Medical Sciences

Background/aim: To describe Graves’ Disease (GD) associated with COVID-19 infection (COVID) or its vaccines (VAC) and to compare the clinical presentations, laboratory parameters, and short-term clinical course of the disease among different etiology groups (COVID, VAC, and GD control).

Materials and methods: Included in this multicenter matched case–control, retrospective cohort study were 239 patients with newly diagnosed (n = 196) or recurrent GD (n = 43) associated with COVID (n = 79) or VAC (n = 160). Each case was matched (1:1) with a control who had been diagnosed with GD prior to COVID.

Results: The median age of the …

Electrochemical Detection Of No And Ca2+ During Cold Atmospheric Plasma Treatment Of Acute Wounds: Sensor Selectivity And Stability In The Plasma-Bio-System, Jonathan E. Thomas, Kristina Pattison, Suneel Kumar, Gagana Karkada, Duncan Trosan, Aunic Goodin, Jason Rainone, Dnyaneshwari Rananavare, Vandana Miller, Francois Berthiaume, Katharina Stapelmann

Kimmel Cancer Center Faculty Papers

Cold atmospheric plasmas (CAP) are a versatile tool in medical applications like wound healing. Its therapeutic benefits are partially attributed to the generation of biologically active reactive oxygen and nitrogen species (RONS). Characterization of RONS, however, typically only occurs after treatment. Here we report the first real-time in situ detection of CAP-generated nitric oxide (NO), and the simultaneous detection of cellular calcium ions (Ca²⁺) release using electrochemical sensors during CAP treatment of murine wounds. In vivo, NO rose rapidly within the first minute of CAP treatment but accumulated less overall than in PBS, reflecting reactions with wound-bed targets. In situ …

Anexelekto (Axl)/Mer Inhibitor Tamnorzatinib In Patients With Relapsed/Refractory Acute Myeloid Leukaemia: Results From A Phase I (Monotherapy) And Phase Ii (Combination With Venetoclax) Clinical Study, Margaret T Kasner, Nigel Courtenay-Luck, Courtney Dinardo, Sean M Post, Praneeth Baratam, George N Magrath, Takaaki Nakamura, Akifumi Fujii, Sergio Prados, Naoki Honda, Mary Mcbride, Paula Edwards-Holmes, Robert Stuart

Faculty, Staff and Student Publications

Introduction: Relapsed/refractory (R/R) acute myeloid leukaemia (AML) is a life-threatening haematological malignancy without effective treatments. Anexelekto (Axl) and Mer receptor tyrosine kinases have emerged as important therapeutic targets in AML for their crucial role in survival of AML cells. Tamnorzatinib (ONO-7475) is a potent and highly selective inhibitor of Axl/Mer. We report first-in-human study of tamnorzatinib (NCT03176277) in patients with R/R AML.

Methods: Tamnorzatinib was administered as monotherapy (n = 20) to determine an appropriate biological dose of tamnorzatinib and then in combination (n = 22) with venetoclax to evaluate safety and clinical efficacy.

Results: Tamnorzatinib was safe …

Stromal Fibroblastic Mutant Trp53 Promotes Mammary Tumor Development Via Enhanced Secretion Of Paracrine Factors, Bin Liu, Shunbin Xiong, Abie Williams-Villalobo, Gilda Chau, Yuan Qi, Hehua Chen, Carenza Johnson, Dhruv Chachad, Joy Mcdaniel, Xiaoping Su, Adel K El-Naggar, Guillermina Lozano, Yun Zhang

Faculty, Staff and Student Publications

Mutations in the tumor suppressor gene TP53 have been identified in breast cancer-associated fibroblasts and are associated with poor patient prognosis. However, the functional impact of fibroblastic mutant p53 on breast cancer development remains unclear. To investigate this, we compared female mice harboring HER2-driven mammary tumors with a fibroblast-specific Trp53 mutation (NP) to those with wild-type fibroblastic Trp53 (N). NP mice exhibited significantly shorter median tumor-free survival than N mice. RNA sequencing of NP and N tumors and mammary glands revealed numerous differentially expressed genes (DEGs) between tumors and the corresponding glands in both genotypes. Notably, the NP tumors showed …

Measurable Imaging-Based Changes In Enhancement Of Intrahepatic Cholangiocarcinoma After Radiotherapy Reflect Physical Mechanisms Of Response, Brian De, Prashant Dogra, Mohamed Zaid, Dalia Elganainy, Kevin Sun, Ahmed M Amer, Charles Wang, Michael K Rooney, Enoch Chang, Hyunseon C Kang, Zhihui Wang, Priya Bhosale, Bruno C Odisio, Timothy E Newhook, Ching-Wei D Tzeng, Hop S Tran Cao, Yun S Chun, Jean-Nicholas Vauthey, Sunyoung S Lee, Ahmed Kaseb, Kanwal Raghav, Milind Javle, Bruce D Minsky, Sonal S Noticewala, Emma B Holliday, Grace L Smith, Albert C Koong, Prajnan Das, Vittorio Cristini, Ethan B Ludmir, Eugene J Koay

Faculty, Staff and Student Publications

Escalated doses of radiotherapy associate with improved local control and overall survival (OS) in intrahepatic cholangiocarcinoma (iCCA), but personalization remains limited because conventional size-based CT criteria correlate poorly with outcomes. We hypothesized that quantitative enhancement measurements would better predict clinical outcomes and guide individualized RT optimization. In a retrospective cohort of 154 patients, we analyzed pre- and post-RT CT scans using quantitative European Association for Study of Liver (qEASL) to derive viable tumor volumes, comparing enhancement-based metrics with size-based RECIST and linking them to outcomes via survival and mathematical modeling. Change in enhancement volume was strongly associated with OS after …

Stakeholder Criteria For Trust In Artificial Intelligence-Based Computer Perception Tools In Health Care: Qualitative Interview Study, Ansh Rai, Meghan E Hurley, John Herrington, Eric A Storch, Casey J Zampella, Julia Parrish-Morris, Anika Sonig, Gabriel Lázaro-Muñoz, Kristin Kostick-Quenet

Faculty, Staff and Students Publications

Background: Computer perception (CP) technologies hold significant promise for advancing precision mental health care systems, given their ability to leverage algorithmic analysis of continuous, passive sensing data from wearables and smartphones (eg, behavioral activity, geolocation, vocal features, and ambient environmental data) to infer clinically meaningful behavioral and physiological states. However, successful implementation critically depends on cultivating well-founded stakeholder trust.

Objective: This study aims to investigate, across adolescents, caregivers, clinicians, and developers, the contingencies under which CP technologies are deemed trustworthy in health care.

Methods: We conducted 80 semistructured interviews with a purposive sample of adolescents (n=20) diagnosed with autism, Tourette …

Structural Basis Of Panx1 Permeation And Positive Modulation By Mefloquine, Yangyang Li, Zheng Ruan, Junuk Lee, Ian Orozco, Edward Zhou, Juan Du, Wei Lü

Department of Biochemistry and Molecular Biology Faculty Papers

Purinergic signaling relies on ATP release through exocytosis and large-pore channels. Large-pore channels permeate both small anions like chloride and large signaling molecules like ATP, but how this broad cargo selectivity is structurally controlled remains elusive. Here we investigate PANX1, a prototypical large-pore channel, and uncover structural plasticity at the extracellular entrance formed by seven tryptophan (W74) residues. The W74 sidechains are flexible, sampling conformations that range from a constricted state permissive only to chloride to a dilated state compatible with ATP. These states are coupled to variable cation-π interactions between W74 and arginine 75 (R75), suggesting a mechanism for …

Retrospective Review Of Metastatic Hormone Receptor-Positive Inflammatory Breast Cancer Patients Reveals Poor Responses To Cyclin Dependent Kinase 4/6 Inhibition, Azadeh Nasrazadani, Rebecca S Tidwell, Megumi Kai, Bora Lim, Vicente Valero, Debu Tripathy, Sadia Saleem, Bisrat G Debeb, Anthony Lucci, Wendy A Woodward, Rachel M Layman

Faculty, Staff and Student Publications

Background: Patients with inflammatory breast cancer (IBC) have aggressive biology and relatively inferior responses to standard-of-care (SOC) therapies. Understanding the efficacy of SOC therapies in IBC is critical to optimize outcomes. Our objective was to assess the progression-free survival (PFS) of metastatic hormone receptor-positive HER2-negative/low (HR+HER2-) IBC patients treated with CDK4/6 inhibitors (CDKIs) and hormonal therapy (HT).

Methods: Data from 58 IBC patients with metastatic HR + /HER2- IBC from a single institution were reviewed. The medians (95% confidence intervals) of overall survival (OS), PFS, and time on treatment (ToT) from the time of CDKI initiation were reported via the …

Seed Amplification Of Msa Alpha-Synuclein Aggregates Preserves The Biological And Structural Properties Of Brain-Derived Aggregates, Fei Wang, Victor Banerjee, Carla Barria, Santiago Ramirez, Tyler Allison, Damian Gorski, Haley Evans, Quynh Nguyen, Danielle Harrison, Rabab Al-Lahham, Nicole De Gregorio Carbonell, Michelle Pinho, Sanne Kaalund, Jonas Folke, Susana Aznar, Luis Concha-Marambio, Mohd Ishtikhar, Venkata Kps Mallampalli, Sandra Pritzkow, Mohammad Shahnawaz, Matthew L Baker, Irina Serysheva, Claudio Soto

Faculty, Staff and Student Publications

Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are characterized by the misfolding and aggregation of alpha-synuclein (αSyn). Compelling evidence showed that αSyn aggregates exist as distinct conformational strains in different synucleinopathies. Recently, we reported that the αSyn Seed Amplification Assay (αSyn-SAA) can amplify and distinguish αSyn strains from PD and MSA. In this study, we investigate whether MSA-seeded, SAA-amplified αSyn fibrils retain the biological and structural properties of the αSyn seeds present in MSA brains. We study the biological activities of both brain-derived and SAA-amplified αSyn aggregates using an αSyn "biosensor" cell model and …

Identification Of Predictive Pretreatment Biomarkers For Neoadjuvant Chemotherapy Response In Latino Invasive Breast Cancer Patients, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos A. Orozco, Sandra Diaz-Casas, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba L. Combita

School of Medicine Faculty Publications

Background: Breast cancer (BC) exhibits significant heterogeneity in incidence and mortality worldwide. Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced BC; however, its efficacy varies by subtype. This study examined the gene expression profiles associated with NAC response in Colombian women with invasive BC. Methods: RNA sequencing of pre-treatment tissues from 58 patients (29 responders and 29 non-responders) identified differentially expressed genes (DEGs) for each molecular subtype, and prognostic performance was evaluated using risk scores. Results: Functional enrichment analysis highlighted the immune system pathways in non-responders. Changes in cytokine target activity and immune cell populations were analyzed to …

The Need To Incorporate Polysubstance Use In Neuropsychopharmacology Research: Biological Lessons And New Opportunities, Max E. Joffe, Susan M. Ferguson, Nick W. Gilpin, Melissa A. Herman, Lori A. Knackstedt, Patrick A. Randall, Abigail G. Schindler, Mary M. Torregrossa, Jennifer A. Rinker

School of Medicine Faculty Publications

Critical evaluation and refinement of animal models is essential for neuroscientists to understand complex physiological and pathological processes related to psychiatric diseases. In general, preclinical studies modeling drug dependence and problematic substance use have been limited to the administration of a single substance; however, there is a growing appreciation that this approach has failed to capture the complexities of humans and has stifled translational efforts. Polysubstance use represents the overwhelmingly common patterns of alcohol and drug use in humans. For example, epidemiological studies generally determine that between 70–95 % of individuals with alcohol use disorder use tobacco daily, and upwards …

Rare Epigenetic Alterations Are Conserved Across Hematopoietic Differentiation Stages After Mycobacterial Infection, Brandon T Tran, Pamela N Luna, Ruoqiong Cao, Duy T Le, Apoorva Thatavarty, Laure Maneix, Bailee N Kain, Scott Koh, Andre Catic, Katherine Y King

Faculty, Staff and Students Publications

Infection leads to durable cell-autonomous changes in hematopoietic stem and progenitor cells (HSPCs), resulting in production of innate immune cells with heightened immunity. The mechanisms underlying this phenomenon, termed central trained immunity, remain poorly understood. We hypothesized that infection induces histone modifications leading to changes in chromatin accessibility that are conserved during differentiation from HSPCs to myeloid progenitors and monocytes. We conducted genome-wide surveillance of histone marks H3K27ac and H3K4me3 and chromatin accessibility in hematopoietic stem cells, multipotent progenitor 3, granulocyte-monocyte progenitors, monocytes and macrophages of naïve and Mycobacterium avium infected mice. Interferon signaling pathways and related transcription factor binding …