Digital Commons Network^™

Proceedings Of The 1st Biannual Bridging The Gaps In Lung Cancer Conference, Narjust Florez, Sandip P Patel, Heather Wakelee, Lyudmila Bazhenova, Erminia Massarelli, Ravi Salgia, Brendon Stiles, Solange Peters, Jyoti Malhotra, Shirish M Gadgeel, Jorge J Nieva, Michelle Afkhami, Fred R Hirsch, Matthew Gubens, Tina Cascone, Benjamin Levy, Joshua Sabari, Hatim Husain, Patrick C Ma, Leah M Backhus, Puneeth Iyengar, Percy Lee, Russell Miller, Jacob Sands, Edward Kim

Faculty, Staff and Student Publications

Lung cancer is the leading cause of cancer death in the US and globally. The mortality from lung cancer has been declining, due to a reduction in incidence and advances in treatment. Although recent success in developing targeted and immunotherapies for lung cancer has benefitted patients, it has also expanded the complexity of potential treatment options for health care providers. To aid in reducing such complexity, experts in oncology convened a conference (Bridging the Gaps in Lung Cancer) to identify current knowledge gaps and controversies in the diagnosis, treatment, and outcomes of various lung cancer scenarios, as described here. Such …

Snap Participation As A Moderator Of Food And Nutrition Security And Combined Cardiometabolic Conditions: A Mixed Regression Approach, Maha Almohamad, Ruosha Li, Natalia I Heredia, Jayna M Dave, Eric E Calloway, Anjail Sharrief, Shreela V Sharma

Faculty, Staff and Student Publications

Objectives: To examine the relationships between food security, nutrition security, Supplemental Nutrition Assistance Program (SNAP) participation, and cardiometabolic outcomes, including hypertension, hyperlipidemia, or diabetes, among low-income U.S. individuals.

Methods: A cross-sectional survey of 486 participants (April–June 2021) assessed food and nutrition security and cardiometabolic outcomes. Mixed-effects logistic regression models adjusted for covariates and included a random effect for state of residence. Moderation analyses evaluated SNAP participation’s impact.

Results: Very low food security was associated with higher odds of having at least one cardiometabolic condition, such as hypertension, hyperlipidemia, or diabetes (AOR = 1.96; 95% CI: 1.04–3.69; p = 0.04). SNAP …

Vasa Previa: Prenatal Diagnosis And The Rationale Behind Using A 5 Cm Distance From Internal Os, Claudio V Schenone, Faezeh Aghajani, Ali Javinani, Eyal Krispin, Yinka Oyelese, Ramesha Papanna, Ramen H Chmait, Alireza A Shamshirsaz

Faculty, Staff and Student Publications

In pregnancies with vasa previa, prenatal diagnosis and pre-labor cesarean delivery are associated with significantly improved perinatal outcomes compared to undetected cases. However, a universally accepted ultrasonographic definition of vasa previa is lacking. Specifically, the distance from the cervical internal os beyond which vaginal delivery can be safely recommended remains to be determined. Field experts and recently published societal guidelines agree that a 2 cm cut-off is suboptimal, given that complete cervical dilation during labor risks unprotected fetal vessels within a 5 cm radius from the internal os. Thus, in the setting of a scarcity of evidence and case reports …

Classification Of Schizophrenia, Bipolar Disorder And Major Depressive Disorder With Comorbid Traits And Deep Learning Algorithms, Xiangning Chen, Yimei Lu, Joan Manuel Cue, Mira V Han, Vishwajit L Nimgaonkar, Daniel R Weinberger, Shizhong Han, Zhongming Zhao, Jingchun Chen

Faculty, Staff and Student Publications

Many psychiatric disorders share genetic liabilities, but whether these shared liabilities can be utilized to classify and differentiate psychiatric disorders remains unclear. In this study, we use polygenic risk scores (PRSs) of 42 traits comorbid with schizophrenia (SCZ), bipolar disorder (BIP), and major depressive disorder (MDD) to evaluate their utilities. We found that combining target specific PRS with PRSs of comorbid traits can improve the classification of the target disorders. Importantly, without inclusion of PRSs from targeted disorders, we can still classify SCZ (accuracy 0.710 ± 0.008, AUC 0.789 ± 0.011), BIP (accuracy 0.782 ± 0.006, AUC 0.852 ± 0.004), …

Detection Of Parasite Dna In Soil Samples From Rural Yucatan, Mexico, Liliana E Villanueva-Lizama, Angela Cruz-Coral, Christian Teh-Poot, Julio Vladimir Cruz-Chan, Rojelio Mejia

Faculty, Staff and Students Publications

The soil is the primary environmental reservoir for many parasites transmitted to humans that cause disease. Our environmental study used a multiparallel real-time quantitative polymerase chain reaction assay to detect parasite DNA in soil collected from the outdoor built environments of 34 houses in rural Yucatan, Mexico. The number of positive houses (n, %) per parasite species was 18 (53%) for Acanthamoeba spp.; four (12%) for Blastocystis spp. and Ascaris lumbricoides; three (9%) for Toxocara canis; and one (3%) for Ancylostoma spp., Trichuris trichiura, Entamoeba histolytica, and Giardia intestinalis. No DNA from Necator americanus, Strongyloides stercoralis, Toxocara cati, or Cryptosporidium …

Integral Roles Of The Tgfβ Signaling Pathway In Uterine Function And Disease, Anna Catherine Unser, Diana Monsivais

Faculty, Staff and Students Publications

The uterus is a complex organ that requires precise signaling networks to mediate functions necessary for homeostasis and reproductive processes. The transforming growth factor β (TGFβ) superfamily regulates integral signaling pathways throughout many physiological processes, including cell proliferation, differentiation, and development. In this review, we summarize the current understanding of how the TGFβ signaling family controls key uterine functions, with a specific focus on the endometrium. These uterine functions include endometrial receptivity, implantation, decidualization, placentation, remodeling, and regeneration. Improving our understanding of the signaling networks that regulate these processes is integral to identifying, diagnosing, and treating uterine and reproductive diseases …

Neutralizing Antibody Immune Correlates For A Recombinant Protein Vaccine In The Covail Trial, Youyi Fong, Lauren Dang, Bo Zhang, Jonathan Fintzi, Shiyu Chen, Jing Wang, Nadine G Rouphael, Angela R Branche, David J Diemert, Ann R Falsey, Cecilia Losada, Lindsey R Baden, Sharon E Frey, Jennifer A Whitaker, Susan J Little, Satoshi Kamidani, Emmanuel B Walter, Richard M Novak, Richard Rupp, Lisa A Jackson, Chenchen Yu, Craig A Magaret, Cindy Molitor, Bhavesh Borate, Tara M Babu, Angelica C Kottkamp, Anne F Luetkemeyer, Lilly C Immergluck, Rachel M Presti, Martín Bäcker, Patricia L Winokur, Siham M Mahgoub, Paul A Goepfert, Dahlene N Fusco, Robert L Atmar, Christine M Posavad, Jinjian Mu, Mat Makowski, Mamodikoe K Makhene, Seema U Nayak, Paul C Roberts, Dean Follmann, Peter B Gilbert

Faculty, Staff and Students Publications

For COVAIL recipients of a coronavirus disease 2019 (COVID-19) Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer.

Targeting Tiam1 Enhances Hippocampal-Dependent Learning And Memory In The Adult Brain And Promotes Nmda Receptor-Mediated Synaptic Plasticity And Function, Francisco A Blanco, Md Ali Bin Saifullah, Jinxuan X Cheng, Carlota Abella, Federico Scala, Karen Firozi, Sanyong Niu, Jin Park, Jeannie Chin, Kimberley F Tolias

Faculty, Staff and Students Publications

Excitatory synapses and the actin-rich dendritic spines on which they reside are indispensable for information processing and storage in the brain. In the adult hippocampus, excitatory synapses must balance plasticity and stability to support learning and memory. However, the mechanisms governing this balance remain poorly understood. Tiam1 is an actin cytoskeleton regulator prominently expressed in the dentate gyrus (DG) throughout life. Previously, we showed that Tiam1 promotes dentate granule cell synapse and spine stabilization during development, but its role in the adult hippocampus remains unclear. Here, we deleted Tiam1 from adult forebrain excitatory neurons (Tiam1^fKO) and assessed …

Distributed Cross-Learning For Equitable Federated Models – Privacy-Preserving Prediction On Data From Five California Hospitals, Tsung-Ting Kuo, Rodney A Gabriel, Jejo Koola, Robert T Schooley, Lucila Ohno-Machado

Faculty, Staff and Student Publications

Quality improvement, clinical research, and patient care can be supported by medical predictive analytics. Predictive models can be improved by integrating more patient records from different healthcare centers (horizontal) or integrating parts of information of a patient from different centers (vertical). We introduce Distributed Cross-Learning for Equitable Federated models (D-CLEF), which incorporates horizontally- or vertically-partitioned data without disseminating patient-level records, to protect patients' privacy. We compared D-CLEF with centralized/siloed/federated learning in horizontal or vertical scenarios. Using data of more than 15,000 patients with COVID-19 from five University of California (UC) Health medical centers, surgical data from UC San Diego, and …

Novel Intraoperative Applications Of Fluorescence Imaging Using Indocyanine Green In Pediatric Urology, Albert S T Lee, Ching Man Carmen Tong

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Near-infrared fluorescence imaging (NIRF) with the use of indocyanine green (ICG) has been recently adopted in pediatric urology after its well-published use in the adult population. As a powerful tool that can help delineate complex anatomy and congenital anomalies, we discuss the various applications of this imaging in minimally invasive and open surgery in pediatric urology.

RECENT FINDINGS: The most reported applications of ICG in pediatric urology are within minimally invasive surgery, particularly varicoceles, renal surgery such as nephrectomies and renal tumor excision, mimicking its use in adult urology. ICG has also been applied to reconstructive urology …

Acute Mecp2 Loss In Adult Mice Reveals Transcriptional And Chromatin Changes That Precede Neurological Dysfunction And Inform Pathogenesis, Sameer S Bajikar, Jian Zhou, Ryan O'Hara, Harini P Tirumala, Mark A Durham, Alexander J Trostle, Michelle Dias, Yingyao Shao, Hu Chen, Wei Wang, Hari Krishna Yalamanchili, Ying-Wooi Wan, Laura A Banaszynski, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene cause Rett syndrome, a severe childhood neurological disorder. MeCP2 is a well-established transcriptional repressor, yet upon its loss, hundreds of genes are dysregulated in both directions. To understand what drives such dysregulation, we deleted Mecp2 in adult mice, circumventing developmental contributions and secondary pathogenesis. We performed time series transcriptional, chromatin, and phenotypic analyses of the hippocampus to determine the immediate consequences of MeCP2 loss and the cascade of pathogenesis. We find that loss of MeCP2 causes immediate and bidirectional progressive dysregulation of the transcriptome. To understand what drives gene downregulation, we …

Braf Mutant Appendiceal Adenocarcinoma Differs From Colorectal Cancer But Responds To Braf-Targeted Therapy, Vinay K Pattalachinti, Emaan Haque, Mahmoud Yousef, Abdelrahman Yousef, Saikat Chowdhury, Michael Overman, Christine M Parseghian, Van K Morris, Bryan Kee, Ryan W Huey, Kanwal Raghav, Colin M Court, John Paul Shen

Faculty, Staff and Student Publications

Appendiceal Adenocarcinoma (AA) is a rare gastrointestinal cancer with no FDA-approved targeted therapies. Here, we retrospectively compare BRAF-mutant AA and colorectal cancer (CRC). BRAF mutation is rare in AA (3%). Unlike CRC, BRAFV600E AA is not associated with poor prognosis, female sex, microsatellite instability, mucinous histology, or poor differentiation. In both cancers, BRAFV600E but not atypical BRAF mutations are mutually exclusive with other Ras-activating mutations. BRAFV600E + EGFR inhibition shows efficacy in BRAFV600E AA (disease control rate = 80%, median progression-free survival = 7.1 months).

Brd7 Loss Reawakens Dormant Metastasis Initiating Cells In Lung By Forging An Immunosuppressive Niche, Jayanta Mondal, Junfeng Zhang, Feng Qing, Shunping Li, Dhiraj Kumar, Jason T Huse, Filippo G Giancotti

Faculty, Staff and Student Publications

Metastasis in cancer is influenced by epigenetic factors. Using an in vivo screen, we demonstrate that several subunits of the polybromo-associated BAF (PBAF) chromatin remodeling complex, particularly Brd7, are required for maintaining breast cancer metastatic dormancy in the lungs of female mice. Brd7 loss induces metastatic reawakening, along with modifications in epigenomic landscapes and upregulated oncogenic signaling. Breast cancer cells harboring Brd7 inactivation also reprogram the surrounding immune microenvironment by downregulating MHC-1 expression and promoting a pro-metastatic cytokine profile. Flow cytometric and single-cell analyses reveal increased levels of pro-tumorigenic inflammatory and transitional neutrophils, CD8+ exhausted T cells, and CD4+ stress …

Advanced External Beam Stereotactic Radiotherapy For Skull Base Reirradiation, He Wang, Fahed M Alsanea, Dong Joo Rhee, Xiaodong Zhang, Wei Liu, Jinzhong Yang, Zhifei Wen, Yao Zhao, Tyler D Williamson, Rachel A Hunter, Peter A Balter, Tina M Briere, Ronald X Zhu, Anna Lee, Amy C Moreno, Jay P Reddy, Adam S Garden, David I Rosenthal, Gary B Gunn, Jack Phan

Faculty, Staff and Student Publications

Background/objectives: Stereotactic body radiation therapy (SBRT) for skull base reirradiation is particularly challenging, as patients have already received substantial radiation doses to the region, and nearby normal organs may have approached their tolerance limit from prior treatments. In this study, we reviewed the characteristics and capabilities of four advanced external beam radiation delivery systems and four modern treatment planning systems and evaluated the treatment plan quality of each technique using skull base reirradiation patient cases.

Methods: SBRT plans were generated for sixteen skull base reirradiation patients using four modalities: the GK plan for the Elekta Leksell Gamma Knife Perfexion/ICON, the …

Infection-Related Hospitalization And Incident Heart Failure: The Atherosclerosis Risk In Communities Study, Rebecca L Molinsky, Amil Shah, Melana Yuzefpolskaya, Bing Yu, Jeffrey R Misialek, Bruno Bohn, David Vock, Richard Maclehose, Barry A Borlaug, Paolo C Colombo, Chiadi E Ndumele, Junichi Ishigami, Kunihiro Matsushita, Pamela L Lutsey, Ryan T Demmer

Faculty, Staff and Student Publications

Background: The immune response to infections may become dysregulated and promote myocardial damage contributing to heart failure (HF). We examined the relationship between infection-related hospitalization (IRH) and HF, HF with preserved ejection fraction, and HF with reduced ejection fraction.

Methods and results: We studied 14 468 adults aged 45 to 64 years in the ARIC (Atherosclerosis Risk in Communities) Study who were HF free at visit 1 (1987-1989). IRH was identified using select International Classification of Diseases (ICD) codes in hospital discharge records and was treated as a time-varying exposure. HF incidence was defined as the first occurrence …

Estrogen Receptor-Α Ablation Reverses Muscle Fibrosis And Inguinal Hernias, Tanvi Potluri, Tianming You, Ping Yin, John Coon, Jonah J Stulberg, Yang Dai, David J Escobar, Richard L Lieber, Hong Zhao, Serdar E Bulun

Faculty, Staff and Student Publications

Fibrosis of the lower abdominal muscle (LAM) contributes to muscle weakening and inguinal hernia formation, an ailment that affects a noteworthy 50% of men by age 75 and necessitates surgical correction as the singular therapy. Despite its prevalence, the mechanisms driving LAM fibrosis and hernia development remain poorly understood. Using a humanized mouse model that replicates the elevated skeletal muscle tissue estrogen concentrations seen in aging men, we identified estrogen receptor-α (ESR1) as a key driver of LAM fibroblast proliferation, extracellular matrix deposition, and hernia formation. Fibroblast-specific ESR1 ablation effectively prevented muscle fibrosis and herniation, while pharmacological ESR1 inhibition with …

A Randomized, Double-Blind, Placebo-Controlled Trial Of Il-7 In Critically Ill Patients With Covid-19, Manu Shankar-Hari, Bruno Francois, Kenneth E Remy, Cristina Gutierrez, Stephen Pastores, Thomas Daix, Robin Jeannet, Jane Blood, Andrew H Walton, Reinaldo Salomao, Georg Auzinger, David Striker, Robert S Martin, Nitin J Anand, James Bosanquet, Teresa Blood, Scott Brakenridge, Lyle L Moldawer, Vidula Vachharajani, Cassian Yee, Felipe Dal-Pizzol, Michel Morre, Frederique Berbille, Marcel Van Den Brink, Richard Hotchkiss

Faculty, Staff and Student Publications

Background: Lymphopenia and failure of lymphocytes to mount an early IFN-γ response correlate with increased mortality in COVID-19. Given the essential role of CD4 helper and CD8 cytotoxic cells in eliminating viral pathogens, this profound loss in lymphocytes may impair patients' ability to eliminate the virus. IL-7 is a pleiotropic cytokine that is obligatory for lymphocyte survival and optimal function.

Methods: We conducted a prospective, double-blind, randomized, placebo-controlled trial of CYT107, recombinant human IL-7, in 109 critically ill, patients with lymphopenia who have COVID-19. The primary endpoint was to assess CYT107's effect on lymphocyte recovery with secondary clinical endpoints including …

The Misalignment Of Incentives In Academic Publishing And Implications For Journal Reform, Jennifer S Trueblood, David B Allison, Sarahanne M Field, Ayelet Fishbach, Stefan D M Gaillard, Gerd Gigerenzer, William R Holmes, Stephan Lewandowsky, Dora Matzke, Mary C Murphy, Sebastian Musslick, Vencislav Popov, Adina L Roskies, Judith Ter Schure, Andrei R Teodorescu

Children’s Nutrition Research Center Staff Publications

For most researchers, academic publishing serves two goals that are often misaligned-knowledge dissemination and establishing scientific credentials. While both goals can encourage research with significant depth and scope, the latter can also pressure scholars to maximize publication metrics. Commercial publishing companies have capitalized on the centrality of publishing to the scientific enterprises of knowledge dissemination and academic recognition to extract large profits from academia by leveraging unpaid services from reviewers, creating financial barriers to research dissemination, and imposing substantial fees for open access. We present a set of perspectives exploring alternative models for communicating and disseminating scientific research. Acknowledging that …

Diet Therapy Abates Mutant Apc And Kras Effects By Reshaping Plasma Membrane Cholesterol Nanodomains, Eunjoo Kim, Alfredo Erazo-Oliveras, Mónica Muñoz-Vega, Natividad R Fuentes, Michael L Salinas, Miranda J George, Roger S Zoh, Martha E Hensel, Bhimanagouda S Patil, Ivan Ivanov, Nancy D Turner, Robert S Chapkin

Faculty, Staff and Student Publications

Cholesterol-enriched plasma membrane domains are known to serve as signaling platforms in a diverse array of cellular processes. However, the link between cholesterol homeostasis and mutant APC-KRas-associated colorectal tumorigenesis remains to be established. Thus, we investigated the impact of Apc-Kras on 1) colonocyte plasma membrane cholesterol homeostasis, order, and receptor nanoclustering, 2) colonocyte cell proliferation, and 3) whether these effects are modulated by select membrane active dietaries (MADs). We observed that oncogenic APC-KRas increased membrane order by perturbing cholesterol homeostasis when cell proliferation is upregulated, in part by altering the expression of genes associated with cholesterol influx, export and de …

Ion Suppression Correction And Normalization For Non-Targeted Metabolomics, Iqbal Mahmud, Bo Wei, Lucas Veillon, Lin Tan, Sara Martinez, Bao Tran, Alexander Raskind, Felice De Jong, Yiwei Liu, Jibin Ding, Yun Xiong, Wai-Kin Chan, Rehan Akbani, John N Weinstein, Chris Beecher, Philip L Lorenzi

Faculty, Staff and Student Publications

Ion suppression is a major problem in mass spectrometry (MS)-based metabolomics; it can dramatically decrease measurement accuracy, precision, and sensitivity. Here we report a method, the IROA TruQuant Workflow, that uses a stable isotope-labeled internal standard (IROA-IS) library plus companion algorithms to: 1) measure and correct for ion suppression, and 2) perform Dual MSTUS normalization of MS metabolomic data. We evaluate the method across ion chromatography (IC), hydrophilic interaction liquid chromatography (HILIC), and reversed-phase liquid chromatography (RPLC)-MS systems in both positive and negative ionization modes, with clean and unclean ion sources, and across different biological matrices. Across the broad range …

Theranostic Nanoemulsions Suppress Macrophage-Mediated Acute Inflammation In Rats, Riddhi Vichare, Yalcin Kulahci, Rebecca Mccallin, Fatih Zor, Fatma Nurefsan Selek, Lu Liu, Caitlin Crelli, Anneliese Troidle, Michele Herneisey, James M Nichols, Andrew J Shepherd, Vijay S Gorantla, Jelena M Janjic

Faculty, Staff and Student Publications

In inflammatory diseases or following an injury, dysregulated inflammation is a common driver of pain and tissue damage. Macrophages are immune cells that contribute to the initiation, maintenance, and resolution of inflammation due to their phenotypic plasticity in response to signals from inflammatory microenvironments. Macrophages infiltrate and polarize toward a pro-inflammatory phenotype (M

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial, Wissam A Jaber, Carin F Gonsalves, Stefan Stortecky, Samuel Horr, Orestis Pappas, Ripal T Gandhi, Keith Pereira, Jay Giri, Sameer J Khandhar, Khawaja Afzal Ammar, David M Lasorda, Brian Stegman, Lucas Busch, David J Dexter, Ezana M Azene, Nikhil Daga, Fakhir Elmasri, Chandra R Kunavarapu, Mark E Rea, Joseph S Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason C Smith, Thomas M Tamlyn, Gabriel A Hernandez, Parth Rali, Torrey R Schmidt, Jeffrey T Bruckel, Juan C Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian A Bergmark, Bhavraj Khalsa, David M Zlotnick, Jordan Castle, David J O'Connor, C Michael Gibson, Peerless Committees And Investigators

Faculty, Staff and Student Publications

Background: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

Methods: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to …

Cancer Cells Avoid Ferroptosis Induced By Immune Cells Via Fatty Acid Binding Proteins, Maria Angelica Freitas-Cortez, Fatemeh Masrorpour, Hong Jiang, Iqbal Mahmud, Yue Lu, Ailing Huang, Lisa K Duong, Qi Wang, Tiffany A Voss, Claudia S Kettlun Leyton, Bo Wei, Wai-Kin Chan, Kevin Lin, Jie Zhang, Efrosini Tsouko, Shonik Ganjoo, Hampartsoum B Barsoumian, Thomas S Riad, Yun Hu, Carola Leuschner, Nahum Puebla-Osorio, Jing Wang, Jian Hu, Michael A Davies, Vinay K Puduvalli, Cyrielle Billon, Thomas P Burris, Philip L Lorenzi, Boyi Gan, James W Welsh

Faculty, Staff and Student Publications

Background: Cancer creates an immunosuppressive environment that hampers immune responses, allowing tumors to grow and resist therapy. One way the immune system fights back is by inducing ferroptosis, a type of cell death, in tumor cells through CD8 + T cells. This involves lipid peroxidation and enzymes like lysophosphatidylcholine acyltransferase 3 (Lpcat3), which makes cells more prone to ferroptosis. However, the mechanisms by which cancer cells avoid immunotherapy-mediated ferroptosis are unclear. Our study reveals how cancer cells evade ferroptosis and anti-tumor immunity through the upregulation of fatty acid-binding protein 7 (Fabp7).

Methods: To explore how cancer cells resist immune cell-mediated …

Spending Changes After Moving To Areas With Greater Aco Participation Among Nonattributed Medicare Beneficiaries, Yucheng Hou, Marisa Elena Domino, Valerie A Lewis, Qing Gong, Kevin Callison, Justin G Trogdon

Faculty, Staff and Student Publications

IMPORTANCE: Accountable care organizations (ACOs) under the Medicare Shared Savings Program have long been envisioned as a pathway to improved care efficiency and quality of care for all Medicare beneficiaries. However, little is known about whether the changes in health care spending associated with ACOs have extended beyond ACO-attributed Medicare beneficiaries to all Medicare beneficiaries.

OBJECTIVE: To estimate spending changes by non-ACO-attributed Medicare beneficiaries after moving to geographic areas with greater ACO participation.

DESIGN, SETTING, AND PARTICIPANTS: This repeated cross-sectional study analyzed claims from a 20% representative sample of all Medicare beneficiaries, aged 65 to 99 years, from 2009 to …

Sleep Trajectories And All-Cause Mortality Among Low-Income Adults, Kelsie M Full, Hui Shi, Loren Lipworth, Lawrence T Dauer, Michael T Mumma, Qian Xiao

Faculty, Staff and Student Publications

IMPORTANCE: Short and long sleep durations are adversely associated with cardiovascular disease (CVD), type 2 diabetes, and mortality. It remains unclear how sleep duration trajectories over time are associated with mortality and whether these associations vary by well-documented sex, race, and socioeconomic sleep disparities.

OBJECTIVE: To investigate the association of 5-year sleep duration trajectories with all-cause and cause-specific mortality among US adults, predominantly those in low-income groups.

DESIGN, SETTING, AND PARTICIPANTS: The Southern Community Cohort Study included participants aged 40 to 79 years recruited and enrolled (from March 2002 to September 2009) from community health centers by using random sampling …

Short Duration Of Antenatal Corticosteroid Exposure And Outcomes In Extremely Preterm Infants, Sanjay Chawla, Myra H Wyckoff, Satyan Lakshminrusimha, Matthew A Rysavy, Ravi Mangal Patel, Dhuly Chowdhury, Abhik Das, Rachel G Greenberg, Girija Natarajan, Seetha Shankaran, Edward F Bell, Namasivayam Ambalavanan, Noelle E Younge, Abbot R Laptook, Leeann R Pavlek, Carl H Backes, Krisa P Van Meurs, Erika F Werner, Waldemar A Carlo, National Institute Of Child Health And Human Development (Nichd) Neonatal Research Network (Nrn)

Faculty, Staff and Student Publications

Importance: When preterm delivery is imminent, it remains unclear whether the timing from administration of antenatal betamethasone to birth may reduce mortality and morbidity among extremely preterm infants.

Objective: To evaluate the association of duration from exposure to first dose of antenatal betamethasone with outcomes among extremely preterm infants.

Design, setting, and participants: This cohort study enrolled infants born at 22 0/7 to 27 6/7 weeks' gestation from January 2016 to February 2021 at National Institute of Child Health and Human Development Neonatal Research Network centers. Infants exposed to multiple doses of antenatal betamethasone, infants who did not receive intensive …

Structural Insights Into Light-Gating Of Potassium-Selective Channelrhodopsin, Takefumi Morizumi, Kyumhyuk Kim, Hai Li, Probal Nag, Tal Dogon, Oleg A Sineshchekov, Yumei Wang, Leonid S Brown, Songhwan Hwang, Han Sun, Ana-Nicoleta Bondar, Igor Schapiro, Elena G Govorunova, John L Spudich, Oliver P Ernst

Faculty, Staff and Student Publications

Structural information on channelrhodopsins' mechanism of light-gated ion conductance is scarce, limiting its engineering as optogenetic tools. Here, we use single-particle cryo-electron microscopy of peptidisc-incorporated protein samples to determine the structures of the slow-cycling mutant C110A of kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) in the dark and upon laser flash excitation. Upon photoisomerization of the retinal chromophore, the retinylidene Schiff base NH-bond reorients from the extracellular to the cytoplasmic side. This switch triggers a series of side chain reorientations and merges intramolecular cavities into a transmembrane K+ conduction pathway. Molecular dynamics simulations confirm K+ flux through the illuminated state …

Combined Clinical, Structural And Cellular Studies Discriminate Pathogenic And Benign Trpv4 Variants, Sarah H Berth, Linh Vo, Do Hoon Kwon, Tiffany Grider, Yasmine S Damayanti, Gage Kosmanopoulos, Andrew Fox, Alexander R Lau, Patrice Carr, Jack K Donohue, Maya Hoke, Simone Thomas, Chafic Karam, Alex J Fay, Ethan Meltzer, Thomas O Crawford, Rachelle Gaudet, Michael E Shy, Ute A Hellmich, Seok-Yong Lee, Charlotte J Sumner, Brett A Mccray

Faculty, Staff and Students Publications

Dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) cause diverse and largely distinct channelopathies, including inherited forms of neuromuscular disease, skeletal dysplasias and arthropathy. Pathogenic TRPV4 mutations cause gain of ion channel function and toxicity that can be rescued by small molecule TRPV4 antagonists in cellular and animal models, suggesting that TRPV4 antagonism could be therapeutic for patients. Numerous variants in TRPV4 have been detected with targeted and whole exome/genome sequencing, but for the vast majority, their pathogenicity remains unclear. Here, we used a combination of clinical information and experimental structure-function analyses to evaluate 30 …

Elevated Micro- And Nanoplastics Detected In Preterm Human Placentae, Michael Jochum, Marcus Garcia, Alexandra Hammerquist, Jacquelyne Howell, Myla Stanford, Rui Liu, Marian Olewine, Eliane El Hayek, Emily Phan, Lori Showalter, Cynthia Shope, Melissa Suter, Matthew Campen, Kjersti Aagaard, Enrico Barrozo

Faculty, Staff and Students Publications

Recent analytical advancements have uncovered increasing micro- and nanoplastics (MNPs) in environmental, dietary, and biological domains, raising concerns about their health impacts. Preterm birth (PTB), a leading cause of maternal and neonatal morbidity and mortality, may be influenced by MNP exposure, yet this relationship remains unexplored. This study quantified 12 MNP polymers in placentae from term (n=87) and preterm (n=71) deliveries using pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). Cumulative MNP concentrations were 28% higher in PTB placentae (mean ±SD: 224.7 ± 180.7 μg/g vs. 175.5 ± 137.9 μg/g; p=0.038). Polyvinyl chloride (PVC), polyethylene terephthalate (PET), polyurethane (PU), and polycarbonate (PC) were significantly …

Update On Cancer Screening In Children With Syndromes Of Bone Lesions, Hereditary Leiomyomatosis And Renal Cell Carcinoma Syndrome, And Other Rare Syndromes, Orli Michaeli, Sun Young Kim, Sarah G Mitchell, Marjolijn C J Jongmans, Jonathan D Wasserman, Melissa R Perrino, Anirban Das, Suzanne P Macfarland, Sarah R Scollon, Mary-Louise C Greer, Nara Sobreira, Bailey Gallinger, Philip J Lupo, David Malkin, Kami Wolfe Schneider, Kris Ann P Schultz, William D Foulkes, Emma R Woodward, Douglas R Stewart

Faculty, Staff and Students Publications

The management of children with syndromes associated with an increased risk of benign and malignant neoplasms is a complex challenge for health care professionals. The 2023 American Association for Cancer Research Childhood Cancer Predisposition Workshop provided updated consensus guidelines on cancer surveillance in these syndromes, aiming to improve early detection and intervention and reduce morbidity associated with such neoplasms. In this article, we review several of the rare conditions discussed in this workshop. Ollier disease and Maffucci syndrome are enchondromatoses (disorders featuring benign bone lesions) with up to 50% risk of malignancy, including chondrosarcoma. These patients require surveillance with baseline …