Medical Specialties Commons^™

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Comprehensive Analysis Of Transcription Factor-Based Molecular Subtypes And Their Correlation To Clinical Outcomes In Small-Cell Lung Cancer, Sehhoon Park, Tae Hee Hong, Soohyun Hwang, Simon Heeke, Carl M Gay, Jiyeon Kim, Hyun-Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Jong Ho Cho, Yong Soo Choi, Jhingook Kim, Young Mog Shim, Hong Kwan Kim, Lauren Averett Byers, John V Heymach, Yoon-La Choi, Se-Hoon Lee, Keunchil Park

Faculty, Staff and Student Publications

BACKGROUND: Recent studies have reported the predictive and prognostic value of novel transcriptional factor-based molecular subtypes in small-cell lung cancer (SCLC). We conducted an in-depth analysis pairing multi-omics data with immunohistochemistry (IHC) to elucidate the underlying characteristics associated with differences in clinical outcomes between subtypes.

METHODS: IHC (n = 252), target exome sequencing (n = 422), and whole transcriptome sequencing (WTS, n = 189) data generated from 427 patients (86.4% males, 13.6% females) with SCLC were comprehensively analysed. The differences in the mutation profile, gene expression profile, and inflammed signatures were analysed according to the IHC-based molecular subtype.

FINDINGS: IHC-based …

C2h2 Zinc Finger Transcription Factors Associated With Hemoglobinopathies, Xing Zhang, Fangfang Xia, Xiaotian Zhang, Robert M Blumenthal, Xiaodong Cheng

Faculty, Staff and Student Publications

In humans, specific aberrations in β-globin results in sickle cell disease and β-thalassemia, symptoms of which can be ameliorated by increased expression of fetal globin (HbF). Two recent CRISPR-Cas9 screens, centered on ∼1500 annotated sequence-specific DNA binding proteins and performed in a human erythroid cell line that expresses adult hemoglobin, uncovered four groups of candidate regulators of HbF gene expression. They are (1) members of the nucleosome remodeling and deacetylase (NuRD) complex proteins that are already known for HbF control; (2) seven C2H2 zinc finger (ZF) proteins, including some (ZBTB7A and BCL11A) already known for directly silencing the fetal γ-globin …

Mitochondrial Regulation Of Gpx4 Inhibition-Mediated Ferroptosis In Acute Myeloid Leukemia, Hiroki Akiyama, Ran Zhao, Lauren B Ostermann, Ziyi Li, Matthew Tcheng, Samar J Yazdani, Arman Moayed, Malcolm L Pryor, Sandeep Slngh, Natalia Baran, Edward Ayoub, Yuki Nishida, Po Yee Mak, Vivian R Ruvolo, Bing Z Carter, Aaron D Schimmer, Michael Andreeff, Jo Ishizawa

Faculty, Staff and Student Publications

Resistance to apoptosis in acute myeloid leukemia (AML) cells causes refractory or relapsed disease, associated with dismal clinical outcomes. Ferroptosis, a mode of non-apoptotic cell death triggered by iron-dependent lipid peroxidation, has been investigated as potential therapeutic modality against therapy-resistant cancers, but our knowledge of its role in AML is limited. We investigated ferroptosis in AML cells and identified its mitochondrial regulation as a therapeutic vulnerability. GPX4 knockdown induced ferroptosis in AML cells, accompanied with characteristic mitochondrial lipid peroxidation, exerting anti-AML effects in vitro and in vivo. Electron transport chains (ETC) are primary sources of coenzyme Q

Dynamic Imaging Of Blood Coagulation Within The Hematoma Of Patients With Acute Hemorrhagic Stroke, Muhammad E Haque, Seth B Boren, James Mills, Kerry G Schneider, Maria Parekh, Stuart M Fraser, Ivo Bach, Praveen Hariharan, Pamela J Zelnick, Felix S Guerra Castanon, Asim Naveed, Muhammad Tariq, Octavio D Arevalo, Khader M Hasan, Miguel Escobar, Xiurong Zhao, Clark Sitton, Ponnada A Narayana, James C Grotta, Jaroslaw Aronowski, Sean I Savitz

Faculty, Staff and Student Publications

BACKGROUND: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making.

METHODS: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, …

New Horizons In Hyperpolarized13c Mri, Myriam M Chaumeil, James A Bankson, Kevin M Brindle, Shdema Epstein, Ferdia A Gallagher, Martin Grashei, Caroline Guglielmetti, Joshua D Kaggie, Kayvan R Keshari, Stephan Knecht, Christoffer Laustsen, Andreas B Schmidt, Daniel Vigneron, Yi-Fen Yen, Franz Schilling

Faculty, Staff and Student Publications

Hyperpolarization techniques significantly enhance the sensitivity of magnetic resonance (MR) and thus present fascinating new directions for research and applications with in vivo MR imaging and spectroscopy (MRI/S). Hyperpolarized 13C MRI/S, in particular, enables real-time non-invasive assessment of metabolic processes and holds great promise for a diverse range of clinical applications spanning fields like oncology, neurology, and cardiology, with a potential for improving early diagnosis of disease, patient stratification, and therapy response assessment. Despite its potential, technical challenges remain for achieving clinical translation. This paper provides an overview of the discussions that took place at the international workshop "New Horizons …

Social And Behavior Factors Of Alzheimer's Disease And Related Dementias: A National Study In The Us, David Ciciora, Elizabeth Vásquez, Edward Valachovic, Lifang Hou, Yinan Zheng, Hua Xu, Xiaoqian Jiang, Kun Huang, Kelley Pettee Gabriel, Hong-Wen Deng, Mary P Gallant, Kai Zhang

Faculty, Staff and Student Publications

Introduction: Considerable research has linked many risk factors to Alzheimer's Disease and Related Dementias (ADRD). Without a clear etiology of ADRD, it is advantageous to rank the known risk factors by their importance and determine if disparities exist. Statistical-based ranking can provide insight into which risk factors should be further evaluated.

Methods: This observational, population-based study assessed 50 county-level measures and estimates related to ADRD in 3,155 counties in the U.S. using data from 2010 to 2021. Statistical analysis was performed in 2022-2023. The machine learning method, eXtreme Gradient Boosting, was utilized to rank the importance of these variables by …

Deep Learning To Predict Rapid Progression Of Alzheimer's Disease From Pooled Clinical Trials: A Retrospective Study, Xiaotian Ma, Madison Shyer, Kristofer Harris, Dulin Wang, Yu-Chun Hsu, Christine Farrell, Nathan Goodwin, Sahar Anjum, Avram S Bukhbinder, Sarah Dean, Tanveer Khan, David Hunter, Paul E Schulz, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

The rate of progression of Alzheimer's disease (AD) differs dramatically between patients. Identifying the most is critical because when their numbers differ between treated and control groups, it distorts the outcome, making it impossible to tell whether the treatment was beneficial. Much recent effort, then, has gone into identifying RPs. We pooled de-identified placebo-arm data of three randomized controlled trials (RCTs), EXPEDITION, EXPEDITION 2, and EXPEDITION 3, provided by Eli Lilly and Company. After processing, the data included 1603 mild-to-moderate AD patients with 80 weeks of longitudinal observations on neurocognitive health, brain volumes, and amyloid-beta (Aβ) levels. RPs were defined …

Cancer Statistics In Korea: Incidence, Mortality, Survival, And Prevalence In 2021, Eun Hye Park, Kyu-Won Jung, Nam Ju Park, Mee Joo Kang, E Hwa Yun, Hye-Jin Kim, Jeong-Eun Kim, Hyun-Joo Kong, Jeong-Soo Im, Hong Gwan Seo

Faculty, Staff and Student Publications

PURPOSE: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2021.

MATERIALS AND METHODS: Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2021, with survival follow-up until December 31, 2022. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea.

RESULTS: The number of new cancer diagnoses in 2021 increased by 27,002 cases (10.8%) compared to 2020. In 2021, newly diagnosed cancer cases and deaths from cancer were reported as 277,523 (age-standardized rate [ASR], 289.3 per …

Prediction Of Cancer Incidence And Mortality In Korea, 2024, Kyu-Won Jung, Mee Joo Kang, Eun Hye Park, E Hwa Yun, Hye-Jin Kim, Jeong-Eun Kim, Hyun-Joo Kong, Jeong-Soo Im, Hong Gwan Seo

Faculty, Staff and Student Publications

PURPOSE: This study aimed to report the projected cancer incidence and mortality for the year 2024 to estimate Korea's current cancer burden.

MATERIALS AND METHODS: Cancer incidence data from 1999 to 2021 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2022 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and multiplying the projected age-specific rates by the anticipated age-specific population for 2024. A joinpoint regression model was used to determine the year in which …

E-Cadherin Loss Drives Diffuse-Type Gastric Tumorigenesis Via Ezh2-Mediated Reprogramming, Gengyi Zou, Yuanjian Huang, Shengzhe Zhang, Kyung-Pil Ko, Bongjun Kim, Jie Zhang, Vishwa Venkatesan, Melissa P Pizzi, Yibo Fan, Sohee Jun, Na Niu, Huamin Wang, Shumei Song, Jaffer A Ajani, Jae-Il Park

Faculty, Staff and Student Publications

Diffuse-type gastric adenocarcinoma (DGAC) is a deadly cancer often diagnosed late and resistant to treatment. While hereditary DGAC is linked to CDH1 mutations, the role of CDH1/E-cadherin inactivation in sporadic DGAC tumorigenesis remains elusive. We discovered CDH1 inactivation in a subset of DGAC patient tumors. Analyzing single-cell transcriptomes in malignant ascites, we identified two DGAC subtypes: DGAC1 (CDH1 loss) and DGAC2 (lacking immune response). DGAC1 displayed distinct molecular signatures, activated DGAC-related pathways, and an abundance of exhausted T cells in ascites. Genetically engineered murine gastric organoids showed that Cdh1 knock-out (KO), KrasG12D, Trp53 KO (EKP) accelerates tumorigenesis with immune evasion …

Protective Effects Of The Postbiotic Lactobacillus Plantarum Md35 On Bone Loss In An Ovariectomized Mice Model, Ju-Yeong Myeong, Hye-Yeon Jung, Hyo-Seok Chae, Hyang Hyun Cho, Don-Kyu Kim, You-Jee Jang, Jae-Il Park

Faculty, Staff and Student Publications

Postmenopausal osteoporosis is caused by estrogen deficiency, which impairs bone homeostasis, resulting in increased osteoclastic resorption without a corresponding increase in osteoblastic activity. Postbiotics have several therapeutic properties, including anti-obesity, anti-diabetic, anti-inflammatory, and anti-osteoporotic effects. However, the beneficial effects of the postbiotic MD35 of Lactobacillus plantarum on bone have not been studied. In this study, we demonstrated that the postbiotic L. plantarum MD35, isolated from young radish water kimchi, influences osteoclast differentiation in mouse bone marrow-derived macrophage (BMM) culture. In addition, it was effective protecting against estrogen deficiency-induced bone loss in ovariectomized (OVX) mice, an animal model of postmenopausal osteoporosis. …

Clinical Efficacy Of Blood Derivatives On Wound Healing: A Systematic Review And Network Meta-Analysis, Yanhong Wu, Guang Peng, Yuzhi Wang, Jianwu Chen, Bin Zhang, Jianbing Tang, Biao Cheng

Faculty, Staff and Student Publications

This study aims to evaluate the clinical effects of different blood derivatives on wound healing using network meta-analysis. PubMed, Embase, OVID, Web of Science, SCOPUS and Cochrane Central were searched to obtain studies about blood derivatives on wound healing until October 2023. R 4.2.0 and Stata 15.0 softwares were used for data analysis. Forty-four studies comprising 5164 patients were included. The results of network meta-analysis showed that the healing area from high to low was GF + ORCCB, ORCCB, GF, PRF, Unnas paste dressing, APG, PRP injection, PRP, PRP + thrombin gel, PPP, HPL, CT. The healing time from low …

Patient Experience Of Head And Neck Surgery With Free Flap Reconstruction., Lillian W. Dattilo, Trinity I. Russell, Chloe B. Warinner, Heather Starmer, Donald J. Annino, Laura A. Goguen, Rosh K. V. Sethi, Ravindra Uppaluri, Melina Windon, Regan W. Bergmark, Eleni M. Rettig

Markey Cancer Center Faculty Publications

IMPORTANCE: Major head and neck surgery with microvascular free tissue transfer reconstruction is complex, with considerable risk of morbidity. Little is known about patients' experiences, including decision-making prior to, and regret following, free flap surgery.

OBJECTIVE: To characterize patient experiences and decision regret of patients undergoing head and neck reconstructive free flap surgery.

DESIGN, SETTING, AND PARTICIPANTS: This mixed-methods cohort study comprising semistructured interviews was conducted June to August 2021 at a single tertiary academic cancer center. Participants underwent head and neck reconstructive surgery with microvascular free tissue transfer (flap) more than 3 months before recruitment (range, 3 months to …

Ic3d Classification Of Corneal Dystrophies-Edition 3, Jayne Weiss, Christopher Rapuano, Berthold Seitz, Massimo Busin, Tero Kivelä, Nacim Bouheraoua, Cecilie Bredrup, Ken Nischal, Harshvardhan Chawla, Vincent Borderie, Kenneth Kenyon, Eung Kweon Kim, Hans Ulrik Møller, Francis Munier, Tim Berger, Walter Lisch

Wills Eye Hospital Papers

PURPOSE: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature.

METHODS: Peer-reviewed publications from 2014 to 2023 were evaluated. The new information was used to update the anatomic classification and each of the 22 standardized templates including the level of evidence for being a corneal dystrophy [from category 1 (most evidence) to category 4 (least evidence)].

RESULTS: Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( …

Accuracy Of Influenza Icd-10 Diagnosis Codes In Identifying Influenza Illness In Children., James W. Antoon, Tess Stopczynski, Justin Z. Amarin, Laura S. Stewart, Julie A. Boom, Leila C. Sahni, Marian G. Michaels, John V. Williams, Janet A. Englund, Eileen J. Klein, Mary A. Staat, Elizabeth P. Schlaudecker, Rangaraj Selvarangan, Jennifer E. Schuster, Geoffrey A. Weinberg, Peter G. Szilagyi, Ariana Perez, Heidi L. Moline, Andrew J. Spieker, Carlos G. Grijalva, Samantha M. Olson, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Studies of influenza in children commonly rely on coded diagnoses, yet the ability of International Classification of Diseases, Ninth Revision codes to identify influenza in the emergency department (ED) and hospital is highly variable. The accuracy of newer International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes to identify influenza in children is unknown.

OBJECTIVE: To determine the accuracy of ICD-10 influenza discharge diagnosis codes in the pediatric ED and inpatient settings.

DESIGN, SETTING, AND PARTICIPANTS: Children younger than 18 years presenting to the ED or inpatient settings with fever and/or respiratory symptoms at 7 …

Transitioning From Afmrd Entrustable Professional Activities To Abfm Core Outcomes To Measure Clinical Preparedness., Bryce A Ringwald

Medical Education Articles

No abstract provided.

Shaping The Future Of Vascular Care: The Evolution Of Advanced Practice Providers (Apps)., Alexandra Moran Baird, Katherine Hays, Danielle Vlazny

Medical Education Articles

No abstract provided.

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations In Chronic Pancreatitis: A Multicenter, Cross-Sectional Study, Kristyn Gumpper-Fedus, Kaylin Chasser, Valentina Pita-Grisanti, Molly Torok, Timothy Pfau, Thomas A Mace, Rachel M Cole, Martha A Belury, Stacey Culp, Phil A Hart, Somashekar G Krishna, Luis F Lara, Mitchell L Ramsey, William Fisher, Evan L Fogel, Chris E Forsmark, Liang Li, Stephen Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Darwin L Conwell, Zobeida Cruz-Monserrate, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Introduction: Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) such as linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations.

Methods: NGAL was measured by immunoassay, and FA composition was measured by gas chromatography in plasma (n = 171) from a multicenter study, including controls (n = 50), acute and recurrent acute pancreatitis (AP/RAP) (n = 71), and CP (n = 50). Peripheral blood mononuclear …

Does A Reduction In Receiving Assistance With Daily Activities Among Older Adults In Mexico Indicate An Increase In Unmet Needs Or A Decrease In Needs For Care?, Brian Downer, Rafael Samper-Ternent, Philip Cantu, Matthew Miller, Rebeca Wong

Faculty, Staff and Student Publications

OBJECTIVES: The percentage of older adults in Mexico with difficulty completing activities of daily living (ADL) who receive assistance from family appears to be decreasing. We compared 2 birth cohorts of older adults in Mexico to investigate whether this trend reflects an increase in unmet caregiving needs or a decrease in the need for care.

METHODS: We selected Mexican Health and Aging Study participants aged 60-76 in 2001 (n = 4,805) and 2018 (n = 6,494). ADL tasks were dressing, walking, bathing, getting in and out of bed, and toileting. Participants who reported difficulty with an ADL were asked if …

The Dementia Care Study (D-Care): Recruitment Strategies And Demographic Characteristics Of Participants In A Pragmatic Randomized Trial Of Dementia Care, Mia Yang, Rafael Samper-Ternent, Elena Volpi, Aval-Na'ree Green, Maya Lichtenstein, Katy Araujo, Pamela Borek, Peter Charpentier, James Dziura, Thomas M Gill, Rebecca Galloway, Erich J Greene, Kristin Lenoir, Peter Peduzzi, Can Meng, Jordan Reese, Amy Shelton, Eleni A Skokos, Jenny Summapund, Erin Unger, David B Reuben, Jeff D Williamson, Alan B Stevens

Faculty, Staff and Student Publications

INTRODUCTION: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare.

METHODS: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients.

RESULTS: Electronic health record (EHR) queries of patients with a diagnosis of dementia and engagement of their clinicians were the main recruitment strategies. A total of 2176 dyads were enrolled, with 80% recruited after the onset of the pandemic. PLWD had a mean age of 80.6 years (SD 8.5), …

Transitioning From An In-Person Intervention To Augmented Text Messaging During Covid-19 In Mexican Americans With Prediabetes: The Starr County Diabetes Prevention Randomized Clinical Trial, Sharon A Brown, Mary A Winter, Heather A Becker, Alexandra A García, Mary M Velasquez, Hirofumi Tanaka, William B Perkison, Eric L Brown, David Aguilar, Craig L Hanis

Faculty, Staff and Student Publications

PURPOSE: The purpose of the study was to explore the feasibility of using commonly available technology, such as text messaging, for diabetes prevention in rural Mexican American communities during COVID-19.

METHODS: Participants were selected from a diabetes prevention study funded by the National Institutes of Health that, prior to COVID-19, involved in-person group intervention sessions. Participants were predominantly female adults born in Mexico and Spanish-speaking. A subsample (n = 140) was divided into 3 cohorts: (1) 50 who completed the initial in-person intervention prior to the COVID-19 research pause, (2) 60 who needed additional support sessions to complete the intervention …

Samhd1 Compound Heterozygous Rare Variants Associated With Moyamoya And Mitral Valve Disease In The Absence Of Other Features Of Aicardi-Goutières Syndrome, Aamuktha R Karla, Amélie Pinard, Maura L Boerio, Dimitri Hemelsoet, Simon J Tavernier, Michel De Pauw, Elke Vereecke, Stuart Fraser, Michael J Bamshad, Dongchuan Guo, Bert Callewaert, Dianna M Milewicz

Faculty, Staff and Student Publications

Aicardi-Goutières syndrome (AGS) is an autosomal recessive inflammatory syndrome that manifests as an early-onset encephalopathy with both neurologic and extraneurologic clinical findings. AGS has been associated with pathogenic variants in nine genes: TREX1, RNASEH2B, RNASEH2C, RNASEH2A, SAMHD1, ADAR, IFIH1, LSM11, and RNU7-1. Diagnosis is established by clinical findings (encephalopathy and acquired microcephaly, intellectual and physical impairments, dystonia, hepatosplenomegaly, sterile pyrexia, and/or chilblains), characteristic abnormalities on cranial CT (calcification of the basal ganglia and white matter) and MRI (leukodystrophic changes), or the identification of pathogenic/likely pathogenic variants in the known genes. One of the genes associated with AGS, SAMHD1, has also …

Premastectomy Radiotherapy And Immediate Breast Reconstruction: A Randomized Clinical Trial, Mark V Schaverien, Puneet Singh, Benjamin D Smith, Wei Qiao, Catherine L Akay, Elizabeth S Bloom, Mariana Chavez-Macgregor, Carrie K Chu, Mark W Clemens, Jessica S Colen, Richard A Ehlers, Rosa F Hwang, Melissa M Joyner, Rene D Largo, Alexander F Mericli, Melissa P Mitchell, John W Shuck, Nina Tamirisa, Debasish Tripathy, Mark T Villa, Wendy A Woodward, Rensi Zacharia, Henry M Kuerer, Karen E Hoffman

Faculty, Staff and Student Publications

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR).

Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR.

Design, setting, and participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible.

Intervention: This …

Final Report Of The Phase Ii Next/Cns-Gct-4 Trial: Gempox Followed By Marrow-Ablative Chemotherapy For Recurrent Intracranial Germ Cell Tumors, Margaret Shatara, Megan Blue, Joseph Stanek, Yin A Liu, Daniel M Prevedello, Pierre Giglio, Vinay K Puduvalli, Sharon L Gardner, Jeffrey C Allen, Kenneth K Wong, Marvin D Nelson, Floyd H Gilles, Roberta H Adams, Jasmine Pauly, Katrina O'Halloran, Ashley S Margol, Girish Dhall, Jonathan L Finlay

Faculty, Staff and Student Publications

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx).

Methods: A total of 9 patients with confirmed …

The Tudor-Knot Domain Of Kat5 Regulates Nucleosomal Substrate Acetylation, Fan Xuan, Hongwen Xuan, Mengying Huang, Wei He, Han Xu, Xiaobing Shi, Hong Wen

Faculty, Staff and Student Publications

The lysine acetyltransferase KAT5 is a pivotal enzyme responsible for catalyzing histone H4 acetylation in cells. In addition to its indispensable HAT domain, KAT5 also encompasses a conserved Tudor-knot domain at its N-terminus. However, the function of this domain remains elusive, with conflicting findings regarding its role as a histone reader. In our study, we have employed a CRISPR tiling array approach and unveiled the Tudor-knot motif as an essential domain for cell survival. The Tudor-knot domain does not bind to histone tails and is not required for KAT5's chromatin occupancy. However, its absence leads to a global reduction in …

Efficacy Of Behavioral Economic Nudges To Assist Teen Mothers: The Healthy Adolescent Transitions Randomized Controlled Trial., Jack Stevens, Joseph Rausch, Robyn Lutz, Ngozi Osuagwu

Women’s Health Articles

Communities may often lack the resources to deliver intensive programs to assist teen mothers, and many eligible adolescents may decline participation in lengthy interventions. Therefore, alternative approaches involving less resource and time may be needed. Behavioral economics (BE) can inform the development of such novel interventions. BE often feature low-intensity approaches designed to "nudge" people to help them reach their long-term goals. Nudges can include giving reminders, making the desired behavior more convenient, and optimizing the verbal presentation of recommended options. Three hundred thirty-one American adolescents (ages 14 to 19) who were 22 to 35 weeks pregnant were enrolled in …

Fear Antiviral Response Pathway Is Independent Of Interferons And Countered By Poxvirus Proteins, Emily A Rex, Dahee Seo, Sruthi Chappidi, Chelsea Pinkham, Sabrynna Brito Oliveira, Aaron Embry, David Heisler, Yang Liu, Moiz Munir, Karolin Luger, Neal M Alto, Flávio Guimarães Da Fonseca, Robert Orchard, Dustin C Hancks, Don B Gammon

Faculty, Staff and Student Publications

The human facilitates chromatin transcription (FACT) complex is a chromatin remodeller composed of human suppressor of Ty 16 homologue (hSpt16) and structure-specific recognition protein-1 subunits that regulates cellular gene expression. Whether FACT regulates host responses to infection remained unclear. We identify a FACT-mediated, interferon-independent, antiviral pathway that restricts poxvirus replication. Cell culture and bioinformatics approaches suggest that early viral gene expression triggers nuclear accumulation of SUMOylated hSpt16 subunits required for the expression of E26 transformation-specific sequence-1 (ETS-1)-a transcription factor that activates virus restriction programs. However, biochemical studies show that poxvirus-encoded A51R proteins block ETS-1 expression by outcompeting structure-specific recognition protein-1 …

Reciprocal Relationships Between Stress And Depressive Symptoms: The Essential Role Of The Nucleus Accumbens, Yizhou Ma, Peter Kochunov, Mark D Kvarta, Tara Legates, Bhim M Adhikari, Joshua Chiappelli, Andrew Van Der Vaart, Eric L Goldwaser, Heather Bruce, Kathryn S Hatch, Si Gao, Shuo Chen, Ann Summerfelt, Thomas E Nichols, L Elliot Hong

Faculty, Staff and Student Publications

BACKGROUND: Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms.

METHODS: In total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006-2010, age = 55.0 ± 7.5 [40-70] years; second visit: 2014-2019; age = 62.7 ± 7.5 [44-80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and …

Rfx Transcription Factor In The Human-Associated Yeast Candida Albicans Regulates Adhesion To Oral Epithelium, Diana L Rodríguez, Elena Lindemann-Perez, J Christian Perez

Faculty, Staff and Student Publications

Adhesion to mucosal surfaces is a critical step in many bacterial and fungal infections. Here, using a mouse model of oral infection by the human fungal pathobiont Candida albicans, we report the identification of a novel regulator of C. albicans adhesion to the oral mucosa. The regulator is a member of the regulatory factor X (RFX) family of transcription factors, which control cellular processes ranging from genome integrity in model yeasts to tissue differentiation in vertebrates. Mice infected with the C. albicans rfx1 deletion mutant displayed increased fungal burden in tongues compared to animals infected with the reference strain. High-resolution …