Digital Commons Network^™

The Impact Of Tracheal Intubation Attempts On Chest Compression Fraction During Pediatric Cpr: A Report From The Videography In Pediatric Resuscitation (Viper) Collaborative, Theerapon Jariyasakoolroj, Karen O'Connell, Thomas Macdonald, John Breslin, Jennifer Murphy, Crystal Macdonald, Tara Neubrand, Laura Rochford, Sage Myers, Benjamin Kerrey, Aaron Donoghue

Faculty, Staff and Students Publications

Aim: To examine the association between tracheal intubation (TI) attempts and chest compression (CC) pauses on chest compression fraction (CCF) during pediatric CPR across a network of emergency departments.

Methods: Prospective observational cohort by the Videography in Pediatric Resuscitation (VIPER) Collaborative. Videorecorded CPR events were reviewed to measure CC pauses and characterize TI attempts. CCF was calculated as the proportion of time compressions were delivered during each event. Events were categorized based on whether TI-associated pauses occurred, and CCF was compared using Wilcoxon rank-sum testing.

Results: A total of 183 CPR events were included. The median event duration was 971 …

Seroprevalence Of Helicobacter Pylori Infection Among Asymptomatic Patients Served By A Safety-Net Healthcare System, Aaron P Thrift, Peyman Dinarvand, Luis Juarez, Jourdan Brown, Daniel Avila, Jennifer Mistica Zafiro Garcia-Villanueva, Lisa C Danek, Hammad Mahmood, Thomas Porter, Ann Gotschall, Noreen F Pirzada, Jaime J Rueda, Lee B Lu, Afroze Ali, Ijeoma Anyakorah, Sanjana J Bhattarai, Anees Fatima, Jessica Garcia, Hung V Nguyen, Bharat Joshi, Malvika Juneja, Misba S Lateef, Najda Mujtaba, Preethi V Nambi, Jay S Orr, Huma Rahman, Stephanie Nguyen, Amna Waqar, Yanyan Chen, David Y Graham, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

Background & aims: Helicobacter pylori screening and eradication is a cost-effective strategy for primary gastric cancer prevention in high-risk populations outside the United States. There is a paucity of population-based H pylori seroprevalence data available in high-risk U.S. groups, particularly data for low-income, uninsured patient populations.

Methods: We used data from a cross-sectional study of a largely underserved, immigrant, and minority patient population. Inclusion criteria included asymptomatic individuals 30-65 years of age without prior H pylori testing or treatment. Consented patients completed a study survey and a blood draw to screen for H pylori using IgG serology. We calculated seroprevalence …

2-Aminobutyrate Mediates The Impact Of Air Pollution On Blood Biomarkers Of Alzheimer’S Disease, Anum Saeed, Chris Mckennan, Jane E Clougherty, Peidi Zhou, Sheila Tripathy, Ellen J Kinnee, Jiaxuan Duan, Kevin Kip, Xuemei Zeng, Victor Villemagne, Tharick Pascoal, Mark Mapstone, Eric A Whitsel, Oscar I Lopez, Christie Ballantyne, Thomas K Karikari, Bing Yu, Steven Reis, Annie Cohen

Faculty, Staff and Students Publications

Introduction: We examined the impact of mid-life metabolites on late-life Alzheimer's disease (AD) plasma biomarkers and whether these metabolites mediate air pollution effects.

Methods: In the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) cohort, we applied high-dimensional regression and meditation models, adjusting for observed and latent confounders, with replication in the Atherosclerosis Risk in Communities (ARIC) study. Exposures included mid-life fine particulate matter (PM2.5), black carbon, metals, and metabolites. Outcomes were: late-life plasma p-tau(181, 217, and 231) and amyloid beta 42/40 (Simoa assays).

Results: In the Heart SCORE study, seven lipid- and amnio acid-pathway metabolites measured in mid-life were …

A Smoking-Related Plasma Protein Score And Smoking-Related Cancer Risk And Mortality In The Atherosclerosis Risk In Communities Study, Meng Ru, Christopher Douville, Aghiles Guenoun, Hana Zahed, Christie M Ballantyne, Kenneth R Butler, Josef Coresh, David J Couper, Panagis Galiatsatos, Marc J Gunter, Ron C Hoogeveen, Mattias Johansson, Corinne E Joshu, P Martijn Kolijn, Christina M Lill, Jiayun Lu, Michael T Marrone, Giovanna Masala, David C Muller, Anna E Prizment, Raul Zamora-Ros, Nilanjan Chatterjee, Adrienne Tin, Elizabeth A Platz

Faculty, Staff and Students Publications

Background: Self-reported smoking may not fully capture individualized risk of smoking-related cancer, but circulating proteins may reflect biological consequences of smoking. Thus, we developed a score based on smoking-related proteins and evaluated its association with smoking-related cancer.

Methods: This prospective cohort study included 10 563 participants aged 47-70 years in the Atherosclerosis Risk in Communities study. Plasma proteins were measured using the SomaScan Platform (SomaLogic Operating Co, Inc). The score was constructed from proteins associated with current smoking, pack-years, or recent quitting identified by linear regression and elastic net regression. Cox regression was used to estimate adjusted hazard ratios and …

Robot-Assisted Resection Of Diaphragmatic And Hepatorenal Recess Peritoneal Endometriosis: Two Cases And A Narrative Review, Xiaoming Guan, Qiannan Yang, Daniel Y Lovell, Chunhua Zhang

Faculty, Staff and Students Publications

In this report, we describe two cases of diaphragmatic endometriosis with concurrent hepatorenal recess peritoneal involvement managed using robotic-assisted laparoscopic surgery with the da Vinci Xi platform. In both patients, diaphragmatic implants and hepatorenal recess peritoneal lesions were excised en bloc, followed by resection of additional pelvic and abdominal lesions. Case 1 involved a 45-year-old woman whose pathology confirmed endometriosis in 28 of 46 sites, including the diaphragm, umbilicus, bowel, hepatorenal recess peritoneum, and pelvic peritoneum. Case 2 involved a 32-year-old woman with histopathologic evidence of endometriosis in 26 of 34 resected sites, including the appendix, diaphragm, hepatorenal recess peritoneum, …

High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology Of Lung Cancer Consortium, Yanhong Liu, Yafang Li, Jinyoung Byun, Vikram R Shaw, Claudio Pikielny, Bo Peng, Chao Cheng, Spiridon Tsavachidis, Xiangjun Xiao, Dakai Zhu, Younghun Han, Ivan P Gorlov, Olga Y Gorlova, Michael Cole, Colette R Gaba, Erin L Crawford, Kristen Purrington, Ellen L Goode, Ping Yang, James Mckay, John K Field, Geoffrey Liu, Rayjean J Hung, Jun Xia, Jiyeon Choi, Matthew B Schabath, Jaclyn Lopiccolo, David C Christiani, Joan Bailey-Wilson, Ann G Schwartz, James C Willey, Diptasri Mandal, Susan M Pinney, Christopher I Amos

Faculty, Staff and Students Publications

Introduction: Rare, deleterious germline variants are key contributors to inherited lung cancer (LC) risk. The Genetic Epidemiology of LC Consortium (GELCC) has curated valuable high-risk LC families and is uniquely positioned to uncover rare, high-penetrance variants underlying familial LC (FLC).

Methods: We performed whole-genome and exome sequencing on germline DNA from 120 high-risk LC families (177 FLC cases, 309 unaffected relatives). We prioritized rare (allele frequency < 1% in the genome aggregation database), potentially deleterious variants present in two or more FLC cases. These variants were then validated in 10,085 sporadic LC (SLC) cases and 612,970 controls.

Results: We identified 118 candidate variants, 28 of which were validated in SLC with strong statistical support. We discovered a novel pathogenic axis of three truncating variants in GALNT6, MUC4, and ERBB3 genes, which …

Stance And Gait Analysis Of Apollo Astronauts On The Moon, Faye Y Chiou-Tan, Conrad Li, Jason P Caffrey, Millard Reschke, Timothy R Macaulay

Faculty, Staff and Students Publications

Introduction/aim: As humans return to the Moon, safe efficient ambulation and fall prevention on the lunar surface are key concerns. The analysis of gait from archived Apollo mission video footage is now possible with pose estimation video analysis software. Thus, this study aims to retrospectively quantify parameters of Apollo astronauts' stance and gait on the Moon.

Methods: Publicly available National Aeronautics and Space Administration (NASA) footage of astronauts ambulating on the Lunar surface was examined using body pose analysis software. Goniometric lower limb joint/torso angles and width of base of stance and gait were derived. Gait cycle stance phase, swing …

Screening For Hypertension And Diabetes In Laundromats In The Largest Hispanic-Majority City In The U.S, Nicholas A Mccann, Vanessa Schick, Jack Tsai

Faculty, Staff and Student Publications

Purpose: This study aimed to assess the prevalence of hypertension and diabetes among laundromat users in San Antonio, Texas, and explore laundromats as a novel setting for health interventions regarding these 2 conditions.

Design: This descriptive, cross-sectional study involved demographic, blood pressure and HbA1c screenings to assess the health status of laundromat users.

Setting: The study took place in 7 laundromats in low-income areas of San Antonio.

Subjects: A total of 150 adults aged 18 and older who regularly used the laundromats and spoke either English or Spanish were eligible to participate.

>Measures: Hypertension was defined as a systolic BP …

Associations Of Blood Biomarkers Of Glial Cell Dysfunction And Neuronal Injury With Future Cognitive Decline And Incident Dementia, Srishti Shrestha, Xiaoqian Zhu, B Gwen Windham, Kevin J Sullivan, Priya Palta, Rebecca F Gottesman, Russell P Tracy, Clifford R Jack, Petrice M Cogswell, Prashanthi Vemuri, Sudha Seshadri, Thomas H Mosley, Michael E Griswold, Myriam Fornage

Faculty, Staff and Student Publications

Introduction: Prospective studies of blood-based biomarkers reflecting pathogenic processes, other than Alzheimer-specific pathologies, that contribute to dementia in diverse cohorts are lacking.

Methods: We jointly fitted linear mixed-effect models and proportional hazards models to examine associations of midlife glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL-40), soluble cluster of differentiation-14 (sCD14), neurofilament light chain (NfL), total tau (t-tau), and ubiquitin C-terminal hydrolase L1 (UCHL1) levels in serum (collected in 1993 to 1995) with cognitive decline and incident dementia (ascertained over 29 years through 2022) in the community-based Atherosclerosis Risk in Communities Study. sCD14 and YKL-40 were measured in 3082 …

Perceived Neighborhood Environment And Objectively Assessed, Habitual Physical Activity Among Us Adults: An All Of Us Research Program Study, Natalia I Heredia, Michael C Robertson, Christopher D Pfledderer, Ethan T Hunt, Timothy J Walker, Deborah Salvo

Faculty, Staff and Student Publications

Introduction: The purpose of this study was to assess the associations between perceived socioenvironmental neighborhood attributes and objectively assessed habitual physical activity among US adults as well as whether associations vary by sociodemographic characteristics.

Methods: We used data from the All of Us research program, a longitudinal cohort study of a diverse sample of Americans. Perceived neighborhood social cohesion, physical and social disorder, walkability, and sociodemographic characteristics were self-reported. Habitual physical activity was ascertained using Fitbit-derived step counts over ≥24 weeks. Generalized additive mixed-effects models were used to test the associations between perceived socioenvironmental neighborhood attributes and daily step counts. …

A Bilingual Ai-Based Chatbot For Nutrition Education In A Food Is Medicine Intervention For High-Risk Pregnant Women: Design And Development Study, Lorena Macias-Navarro, Nalini Ranjit, Gregory W Bounds, Brendon A Providence, Yesmeena Shmaitelly, Naomi M Tice, Shreela V Sharma

Faculty, Staff and Student Publications

Background: Conversational agents (artificial intelligence [AI]-based chatbots) offer a novel approach to health interventions by providing personalized, adaptive interactions that improve over time based on user engagement. In nutrition education, given the wide variation in knowledge, skills, and abilities across participants, AI-based chatbots have the potential to enhance accessibility, engagement, and behavior change. Food is Medicine (FIM) interventions, which aim to improve food security and diet quality among multicultural, at-risk populations, often face challenges related to sustained engagement and use.

Objective: This paper describes the design, development, and iterative refinement of a bilingual AI-driven nutrition chatbot integrated into an FIM …

The Rodent Electronic Nicotine Delivery System (Rends): Effects Of Age On Self-Administration Of Inhaled Nicotine In Female Rats, Daniel Santos Da Silva

All Graduate Theses and Dissertations, Fall 2023 to Present

Smoking tobacco is the leading avoidable cause of death and drives many health problems. Nicotine, the main chemical in tobacco products, keeps people using it. This study used the Rat Electronic Nicotine Delivery System (RENDS), an inexpensive and freely shared, to examine e-cigarette use in adolescent and adult female rats by exploring four phases of nicotine delivered and not delivered to understand use patterns among ages. Our study found that both adolescent and adult female rats chose to inhale nicotine when given the opportunity, showing drug-seeking behavior. Overall, nicotine use was similar between ages. These results could help inform therapies, …

Maternal Low-Sodium Diet Impairs Hippocampal Neurogenesis And Cognition In Adult Mouse Offspring., Xingrao Ke, Connie C. Grobe, Justin L. Grobe, Wei Yu, John J. Reho, Kaela Varberg, Robert H. Lane, Jeffrey L. Segar

Manuscripts, Articles, Book Chapters and Other Papers

Sodium (Na) homeostasis is critical for organ and cell function. Although low maternal Na intake during gestation is associated with low offspring survival rates and birth weights, the long-term impact on neurocognitive function is not known. Identifying a relationship between perinatal Na dysregulation and adult behavioral and cognitive outcomes may be important given the prevalence of both dysnatremias and neurocognitive impairment in preterm infants. This study aimed to determine the association between maternal low Na intake (LSI) and hippocampal-dependent behaviors in mice. C57BL/6J dams were fed a standard (0.30%) or low (0.04%) Na diet from postnatal day 0 until postnatal …

The Resilient Study: A Retrospective, Descriptive, Correlational Investigation Of Correlates Of Oral Endocrine Therapy Adherence In Older Women With Breast Cancer., Sunny Y. Ruggeri, Cynthia L. Russell Lippincott, Gregory L. Alexander, Rebecca J. Bartlett Ellis, Steven R. Chesnut, Lori A. Erickson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Breast cancer is the most prevalent and costly cancer. Oral endocrine therapy (OET) improves survival rates and quality of life while reducing recurrence, mortality, morbidity, and medical costs. However, adherence to OET is challenging because OET is prescribed for 5-10 years. Determinants of OET nonadherence (NA) among women aged 65 and older remain poorly characterized. Existing studies are limited, often focusing on small, single-site samples and focusing on patient-level rather than multi-level determinants. Despite the unique needs of older women, research on OET-NA remains scarce.

OBJECTIVE: This study identified multi-level determinants of OET-NA in older women using ecological systems …

Accelerated Weaning Of Opioids To Reduce Pharmacologic Exposure For Neonatal Opioid Withdrawal Syndrome: A Randomized Clinical Trial., Abbot R. Laptook, Adam Czynski, Rouba Chahine, Rachel G. Greenberg, P Brian Smith, Erica Oliveira, Jenna Gabrio, Barry Eggleston, Abhik Das, Jeannette Lee, Barry Lester, Dave Clark, Michele Walsh, Helen Ko, Clare Campbell Asher, Hayley Friedman, Samuel Gentle, Karishma Rao, Anup Katheria, Kristen Benninger, Sanket Jani, Mark Cody Smith, Akram Khan, Ajay Talati, Shaina Lodhi, Fernando Mena, Amanda England, Prabhu Parimi, Ranjit Kylat, Heidi Harmon, Javed Mannan, Meghan P. Howell, Tanner Wright, Jessica Snowden, Act Now Collaborative

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To determine if newborns receiving morphine or methadone as the primary pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS) tolerate and receive fewer days of opioid using an accelerated wean protocol (15% decrements) compared with using a slower wean protocol (10% decrements).

STUDY DESIGN: Newborns ≥36 weeks of gestation receiving morphine or methadone for NOWS were enrolled in a pragmatic blinded, randomized multicenter trial. Newborns underwent protocol-driven weaning with decreasing opioid doses of either 15% or 10% decrements. Weaning was encouraged every 24 hours, and if signs of NOWS worsened, the preceding dose was resumed. To maintain blinding, the …

Targeted Epigenome Sequencing Of Eosinophils Reveals Cpg Sites And Regulatory Variants Associated With Asthma., Rébecca Dionne-Gagné, Anne-Marie Madore, Anne-Marie Boucher-Lafleur, Tomi Pastinen, Catherine Laprise

Manuscripts, Articles, Book Chapters and Other Papers

Eosinophils are pro-inflammatory cells that play a central role in asthmatic inflammation. However, few studies have examined their methylation profiles in asthma, all relying on microarray-based approaches. Here, an epigenome-wide association study in 183 purified eosinophil samples from the Saguenay-Lac-Saint-Jean asthma family cohort was performed using a custom sequencing panel targeting 4,609,564 CpGs in immune regulatory regions. Two CpG sites in MAEA and SLC9A2 genes, known to be involved in immune function, were significantly associated with asthma, while five additional sites showed suggestive associations. Integration with genotype data (7,829,429 variants) and expression counts (17,513 genes) identified significant quantitative trait loci-mediated …

Leading With Hope: A Clinical Communication Campaign To Promote Partner Hiv Testing In Assisted Partner Notification And Antenatal Care Programs In Uganda., Emily A. Hurley, Violet Gwokyala, Linda Kisaakye Nabitaka, Jolly Beyeza Kashesya, Mercylynn Agasha, Florence Namaganda, Nikolaus Schuetz, J Nalubega Ross, Joseph K B Matovu, Rhoda Wanyenze, Glenn Wagner, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

Among heterosexual couples in sub-Saharan Africa, fears of relationship dissolution and inability to bear healthy children following an HIV-positive result remain barriers to HIV testing. Recently expanded availability of pre-exposure prophylaxis (PrEP) affords a critical opportunity to promote HIV testing with reassuring communication that highlights use for relationship preservation and healthy childbearing. We aimed to develop a theoretically-grounded communication intervention to promote partner HIV testing within assisted partner notification (APN) and antenatal care (ANC) programs in Uganda. Through an 18-month iterative co-creation process, we developed the HOPE Clinical Communication Campaign (HOPE-CCC) in collaboration with a project advisory board (PAB) of …

Treatment Of Haemophilia A Without Inhibitors: Real-World Treatment Patterns And Clinical Outcomes In The Us., Allison P. Wheeler, Lauren Amos Md, Shveta Gupta, Sylvie Bozzi, Gandarvaka Miles, Kalyani Hawaldar, Andrew Wilson, Gillian Hanson, Emily Cibelli, Amanda Wilson, Siddhi Umarje, Anne-Laure Tardy, Jennifer Dumont, Graham Neill, Alix Arnaud

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Despite available prophylactic therapies for haemophilia A, breakthrough bleeding and consequent pain and joint damage still occur.

AIM: To provide insights into the unmet treatment needs of people with moderate-to-severe haemophilia A in the US.

METHODS: For this descriptive, observational cohort study, eligible participants diagnosed with moderate-to-severe haemophilia A were enrolled in the PicnicHealth database on or before 3 October 2022. Three patient groups were established to identify: (1) treatment patterns; (2) clinical outcomes by therapy class (standard half-life [SHL] factor VIII [FVIII]; extended half-life FVIII [EHL]; emicizumab); (3) health-related quality of life (HRQoL) using the Patient-Reported Outcomes Measuring …

Natural Maternal Immunity Protects Neonates From Escherichia Coli Sepsis., Raymond E. Diep, Ujjwal Adhikari, Kubra Gokce Tezel, Giang Pham, Allison R. Burrell, Mary A. Staat, Nguyen Thi Khanh Nhu, Minh-Duy Phan, Kate M. Peters, Mark A. Schembri, Scott H. Saunders, David B. Haslam, John J. Erickson, Susana Chavez-Bueno, Sing Sing Way

Manuscripts, Articles, Book Chapters and Other Papers

Escherichia coli is a leading cause of neonatal sepsis, with infection occurring in approximately one in every 1,000 live births. However, with E. coli colonization beginning soon after birth and defects in neonatal host defence maturation, an alternative consideration is why infection does not occur even more frequently. Here we show that newborn babies with E. coli sepsis have selectively reduced vertically transferred natural antibodies that recognize E. coli, mechanistically explaining their susceptibility to infection. Complementary preclinical studies show that preconceptual intestinal colonization with probiotic E. coli Nissle 1917 (EcN) primes anti-E. coli immunoglobulin G (IgG) antibodies with broad cross-reactivity …

Functional Heterogeneity In Trophoblast Stem Cells Derived From Recurrent Pregnancy Loss Products Of Conception., Qi Fu, Keisuke Kozai, Xingrao Ke, Joe Varberg, Sheng Xia, Ashley S. Howard, Michael Lydic, Kristin Holoch, Courtney Marsh, Elin Grundberg, Kaela Varberg

Manuscripts, Articles, Book Chapters and Other Papers

Recurrent pregnancy loss (RPL), defined as two or more consecutive miscarriages, affects 1-5% of couples attempting to conceive and most frequently occurs between 6 and 8 weeks of gestation, coinciding with critical stages of placental development. Despite this temporal association, placental contributions to RPL pathogenesis remain poorly understood. We hypothesized that trophoblast lineage development, including extravillous trophoblast (EVT) and syncytiotrophoblast (STB) differentiation, are disrupted in RPL. To test this hypothesis, we established and functionally characterized human trophoblast stem (TS) cell lines derived from products of conception (POC) obtained from consenting idiopathic RPL cases. Four TS cell lines were successfully derived …

Regional Variation Of Underlying Kidney Diseases In Children Undergoing Chronic Kidney Replacement Therapy Around The Globe., Dagmara Borzych-Dużałka, Marjolein Bonthuis, Uma Ali, Yok-Chin Yap, Michael Manno, Yihui Zhai, Reyner Loza, Seema Hashmi, Naye Choi, Kenza Soulami, Judith Exantus, Mohamed S. Al Riyami, Sameh Mabrouk, Marbella Ma Angeles, Cristina Zelaya-Camacho, Henny Adriani Puspitasari, Syed Saimul Huque, Francisco Cano, Kar Hui Ng, Sevcan A. Bakkaloğlu, Jerome Harambat, Kitty J. Jager, Bradley A. Warady, Franz Schaefer

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: There is a scarcity of information regarding the distribution of the diseases leading to kidney failure (KF) in children living in the emerging world. We used registry data to provide a global overview of the underlying disease spectrum in children commencing kidney replacement therapy (KRT).

METHODS: We analyzed KF causes among 23,620 children and adolescents commencing maintenance KRT in 80 countries, using data from the IPNA Global KRT Registry (including ESPN/ERA Registry), the International Pediatric Dialysis Network (IPDN), the United States Renal Data System (USRDS), and the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA). The analysis considered …

Cognitive Behavioral Therapy For Individuals With Low Literacy And Perinatal Depression: A Randomized Clinical Trial, Eliza Kleban, Ashleen Lee, Aminata Koroma, D Taylor Hendrixson, Joshua Duncan, Mark J Manary, Kevin B Stephenson

2020-Current year OA Pubs

IMPORTANCE: Perinatal depression is common in sub-Saharan Africa, yet treatment gaps are substantial. Cognitive behavioral therapy (CBT) is effective but relies on written materials.

OBJECTIVE: To evaluate the efficacy of a culturally adapted CBT intervention delivered by lay counselors to women with perinatal depression in rural Sierra Leone.

DESIGN, SETTING, AND PARTICIPANTS: This study was an individually randomized, outcomes assessor- and investigator-blinded, clinical trial of an adapted CBT intervention vs enhanced usual care. The trial was conducted in 6 government-run antenatal clinics in Pujehun District, Sierra Leone, which has limited infrastructure, low literacy, high maternal undernutrition, and no perinatal mental …

Hematopoietic Cell Transplant Access And Patient Diversity, Rachel Cusatis, Ramzi Abboud, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Allogeneic hematopoietic cell transplant (HCT) is curative for hematologic cancers, yet access remains inequitable for racially and ethnically underrepresented and socioeconomically disadvantaged populations, making the goal of having a suitable donor for every patient who needs a transplant challenging. The ACCESS trial broadened access by enrolling patients without matched donors, who instead received an HCT from a mismatched unrelated donor.

OBJECTIVE: To compare baseline characteristics of ACCESS trial participants with participants enrolled in a similar clinical trial and a patient-reported outcome (PRO) protocol cohort.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included adult participants (aged ≥18 years) from 3 …

Defining The Qualities Of A Surgical Resident Who "Gets It": A Qualitative Analysis Of Faculty And Resident Perceptions, Shaleen V Sathe, Ravi R Agrawal, Jennifer Yu, Paul E Wise, Michael Awad, Kevin Y Pei

2020-Current year OA Pubs

BACKGROUND: The phrase "getting it" is frequently used in surgical trainee assessment, yet its meaning remains undefined. This study explores how residents and faculty define the concept and whether perceptions align.

METHODS: Semi-structured interviews were conducted with 11 residents and 13 faculty at a single institution and analyzed using reflexive thematic analysis.

RESULTS: Residents described "getting it" as clinical competence, social awareness, feedback responsiveness, and team integration, while noting challenges with interpreting implicit expectations and the influence of faculty bias. Faculty described "getting it" as a gestalt recognition of initiative, insight, and sound clinical judgment. Both agreed that the concept …

A Covalent Allosteric Molecular Glue Suppresses Nrf2-Dependent Cancer Growth, Nilotpal Roy, Ilah Bok, Harit Panda, Dhaval P Bhatt, Emily M Wilkerson, Soma Saeidi, Paul Zolkind, Michael B Major, Et Al.

2020-Current year OA Pubs

UNLABELLED: The NRF2 transcription factor is constitutively active in cancer, in which it functions to maintain oxidative homeostasis and reprogram cellular metabolism. NRF2-active tumors exhibit NRF2 dependency and resistance to chemotherapy/radiotherapy (RT). In this study, we characterize VVD-065, a first-in-class NRF2 inhibitor that acts via an unprecedented allosteric molecular glue mechanism. In the absence of stress or mutation, NRF2 is rapidly degraded by the Kelch-like ECH-associated protein 1 (KEAP1)-cullin3 (CUL3) ubiquitin-ligase complex. VVD-065 specifically and covalently engages Cys151 on KEAP1, which in turn promotes KEAP1-CUL3 complex formation, leading to enhancement of NRF2 degradation. Previously reported Cys151-directed compounds decrease KEAP1-CUL3 interactions …

Androgen Loss Accelerates Brain Tumour Growth Via Hpa Axis Activation, Juyeun Lee, Joshua B Rubin, Et Al.

2020-Current year OA Pubs

Many cancers, including glioblastoma (GBM), show a male-biased incidence and associated worse outcomes

Crispr-Cas9 Cd33-Deleted Allogeneic Hematopoietic Cell Transplantation With Gemtuzumab Ozogamicin Maintenance In Aml: A Phase 1/2 Trial, John F Dipersio, Et Al.

2020-Current year OA Pubs

Patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are likely to relapse despite allogenic hematopoietic cell transplantation (HCT). Post-HCT preventative maintenance can be limited by toxicity toward the normal donor cells. Tremtelectogene empogeditemcel (trem-cel) is a CRISPR-Cas9 gene-edited allogeneic HCT product lacking CD33, designed to shield the donor graft from cytotoxicity of subsequent CD33-targeted therapies such as gemtuzumab ozogamicin (GO). In this multicenter, phase 1/2a, open-label study, adult patients with AML/MDS with high relapse risk received trem-cel after myeloablative conditioning followed by GO maintenance (0.5-2.0 mg m

Adaptive Evolution Of Gene Regulatory Networks In Mammalian Neocortex, Zhuo Li, Linda J Richards, Et Al.

2020-Current year OA Pubs

Mammals have evolved a more complex brain, exemplified by the transformation of the single-layer dorsal cortex of excitatory projection neurons (ExNs) in ancestors into a multilayered cerebral neocortex

Single-Cell Spatiotemporal Dissection Of The Human Maternal-Fetal Interface, Cheng Wang, Sarah K England, David K Stevenson, Gary M Shaw, Et Al.

2020-Current year OA Pubs

The human maternal-fetal interface is characterized by mosaic intermingling of maternal and fetal cells

Preterm Birth Increases Susceptibility To Hyperglycemia-Induced Kidney Injury With Sex-Specific Differences In Structural And Molecular Responses, Rachel K Dailey, Aleksandra Cwiek, Logan C Hamil, Sage Timberline, Ayyappa Kumar Sista Kameshwar, Masako Suzuki, Jaya Isaac, Kimberly Deronde, Mark Conaway, Kevin M Bennett, Edwin J Baldelomar, Matthew R Hoch, Kimberly J Reidy, Jennifer R Charlton

2020-Current year OA Pubs

BACKGROUND: Preterm birth increases the long-term risk of diabetes and chronic kidney disease (CKD), yet its impact on diabetic kidney disease (DKD) is unclear. We previously showed that male preterm mice with diabetes develop early features of DKD, including reduced podocyte density, decreased renin expression, activation of angiogenesis pathways, and impaired endothelial-podocyte signaling. Here, we examine whether preterm birth similarly accelerates DKD progression in female mice and compare structural and transcriptomic outcomes in the females to the prior male cohort to assess sex-specific differences.

METHODS: Preterm mice were delivered by Caesarean section at 19 days post conception (dpc) and term …