Digital Commons Network^™

Peripheral And Central Kynurenine Pathway Abnormalities In Major Depression, Elisabeth R Paul, Lilly Schwieler, Sophie Erhardt, Sandra Boda, Ada Trepci, Anna Asratian, Adam Yngve, Robert Dantzer, Markus Heilig, J Paul Hamilton, Martin Samuelsson

Faculty, Staff and Student Publications

Considerable data relate major depressive disorder (MDD) with aberrant immune system functioning. Pro-inflammatory cytokines facilitate metabolism of tryptophan along the kynurenine pathway (KP) putatively resulting in reduced neuroprotective and increased neurotoxic KP metabolites in MDD, in addition to modulating metabolic and immune function. This central nervous system hypothesis has, however, only been tested in the periphery. Here, we measured KP-metabolite levels in both plasma and cerebrospinal fluid (CSF) of depressed patients (n = 63/36 respectively) and healthy controls (n = 48/33). Further, we assessed the relation between KP abnormalities and brain-structure volumes, as well as body mass index (BMI), an …

Stem Cell Architecture Drives Myelodysplastic Syndrome Progression And Predicts Response To Venetoclax-Based Therapy, Irene Ganan-Gomez, Hui Yang, Feiyang Ma, Guillermo Montalban-Bravo, Natthakan Thongon, Guillaume Richard-Carpentier, Ganiraju Manyam, Feng Wang, Ana Alfonso, Shuaitong Chen, Caleb Class, Rashmi Kanagal-Shamanna, Justin P Ingram, Yamini Ogoti, Ashley Rose, Sanam Loghavi, Pamela Lockyer, Benedetta Cambo, Muharrem Muftuoglu, Sarah Schneider, Vera Adema, Michael Mclellan, John Garza, Matteo Marchesini, Nicola Giuliani, Matteo Pellegrini, Jing Wang, Jason Walker, Ziyi Li, Koichi Takahashi, Joel D Leverson, Carlos Bueso-Ramos, Michael Andreeff, Karen Clise-Dwyer, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

Myelodysplastic syndromes (MDS) are heterogeneous neoplastic disorders of hematopoietic stem cells (HSCs). The current standard of care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, almost 50% of MDS patients fail HMA therapy and progress to acute myeloid leukemia, facing a dismal prognosis due to lack of approved second-line treatment options. As cancer stem cells are the seeds of disease progression, we investigated the biological properties of the MDS HSCs that drive disease evolution, seeking to uncover vulnerabilities that could be therapeutically exploited. Through integrative molecular profiling of HSCs and progenitor cells in large patient cohorts, we found …

Brain Stereotactic Radiosurgery Using Mr-Guided Online Adaptive Planning For Daily Setup Variation: An End-To-End Test, Eun Young Han, He Wang, Tina Marie Briere, Debra Nana Yeboa, Themistoklis Boursianis, Evangelos Pappas, Jinzhong Yang

Faculty, Staff and Student Publications

Online magnetic resonance (MR)-guided radiotherapy is expected to benefit brain stereotactic radiosurgery (SRS) due to superior soft tissue contrast and capability of daily adaptive planning. The purpose of this study was to investigate daily adaptive plan quality with setup variations and to perform an end-to-end test for brain SRS with multiple metastases treated with a 1.5-Tesla MR-Linac (MRL). The RTsafe PseudoPatient Prime brain phantom was used with a delineation insert that includes two predefined structures mimicking gadolinium contrast-enhanced brain lesions. Daily adaptive plans were generated using six preset and six random setup variations. Two adaptive plans per daily MR image …

Monitoring Malignant T-Cell Clones By Direct Tcr Expression Assay In Patients With Leukemic Cutaneous T-Cell Lymphoma During Extracorporeal Photopheresis, Xiao Ni, Sourindra Maiti, Alissa Redko, Pedram Bijani, Madeleine Duvic

Faculty, Staff and Student Publications

Background/purpose: Accurate assessment of malignant T-cell clones in patients with leukemic cutaneous T-cell lymphoma (L-CTCL) is crucial for diagnosis, treatment, and monitoring disease. Although multiple approaches to quantitate malignant T-cell clones have been reported, a cost-effective assay with broad coverage is not available. We report a NanoString-nCounter-Technology-based direct TCR expression assay (DTEA) that was previously developed to quantify both TCR-Vα and TCR-Vβ usages after adoptive immunotherapy. This study was performed to test the effectiveness of DTEA in assessing malignant T-cell clones in L-CTCL patients.

Methods: Total RNAs extracted from peripheral blood mononuclear cells of patients before starting extracorporeal photopheresis (ECP) …

Zanubrutinib For Treatment-Naïve And Relapsed/Refractory Chronic Lymphocytic Leukaemia: Long-Term Follow-Up Of The Phase I/Ii Au-003 Study, Gavin Cull, Jan A Burger, Stephen Opat, David Gottlieb, Emma Verner, Paula Marlton, Patrick Johnston, David Simpson, Jennifer C Stern, Radha Prathikanti, Kenneth Wu, William Novotny, Jane Huang, Constantine S Tam

Faculty, Staff and Student Publications

The phase I/II AU-003 study in patients with treatment-naïve (TN) or relapsed/refractory (R/R) chronic lymphocytic leukaemia/small lymphocytic lymphoma demonstrated that zanubrutinib therapy results in clinically meaningful and durable responses with acceptable safety and tolerability. We report updated safety and efficacy data for 123 patients with a median follow-up of 47·2 months. Patients received zanubrutinib 160 mg twice daily (81 patients), 320 mg once daily (40), or 160 mg once daily (two). Discontinuations due to adverse events or disease progression were uncommon. The overall response rate (ORR) was 95·9% (TN, 100%; R/R, 95%) with 18·7% achieving complete response (CR). Ongoing response …

The Mesencephalic Locomotor Region Recruits V2a Reticulospinal Neurons To Drive Forward Locomotion In Larval Zebrafish, Jake Howitt

Faculty, Staff and Student Publications

Although the topics of surgical techniques and medical therapies have been widely studied in aortic dissection (AD), studies examining the short- and long-term impact of this event on mental health are largely lacking. Many of the studies have used the 36-Item Short Form Survey at variable time points after the event. However, AD as medical trauma has a complex impact on a person's identity. Its implications for emotional, mental, social, existential, and self-concept could be explored more robustly. This topic was identified as a topic of interest by the AD Collaborative. The AD Collaborative Mental Health Working Group was formed …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Manouchehr Hessabi, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD+GI), 10 children with ASD but no GI symptoms (ASD−GI), and 20 from typically developing (TD) children (TD) in this pilot study. Fecal mycobiome taxa were analyzed by ITS sequencing. GI symptoms (GI Severity Index (GSI)), behavioral symptoms (Social Responsiveness Scale −2 (SRS-2)), inflammation and fungal immunity (fecal calprotectin and serum dectin-1 (ELISA)) were evaluated. …

Nonjudgmental Acceptance: Associations With Substance-Related Cue Reactivity In Adults With Substance Use Disorders And Posttraumatic Stress, Scott D Lane

Faculty, Staff and Student Publications

The present investigation examined the predictive utility of nonjudgmental acceptance, a facet of mindfulness defined as the ability to remain aware and nonevaluative about internal experience, in terms of substance-related cue reactivity among adults with substance use disorders (SUD) and posttraumatic stress (PTS) symptomatology. We hypothesized that higher nonjudgmental acceptance, indexed via self-report, would predict higher levels of self-reported control over oneself and safety 'in the moment', broadly, and lower levels of substance-related craving in response to substance script cues. Effects were expected after subtracting reactivity to neutral script cues from each outcome rating. PTS severity was included as a …

Wavelet Analysis Reveals Differential Lower Limb Muscle Activity Patterns Long After Anterior Cruciate Ligament Reconstruction

Faculty, Staff and Student Publications

The purpose of this study was to test whether differences in muscle activity patterns between anterior cruciate ligament-reconstructed patients (ACLR) and healthy controls could be detected 10 to 15 years post-surgery using a machine learning classification approach. Eleven ACLR subjects and 12 healthy controls were recruited from an ongoing prospective randomized clinical trial. Surface electromyography (EMG) signals were recorded from gastrocnemius medialis and lateralis, tibialis anterior, vastus medialis, rectus femoris, biceps femoris, and semitendinosus muscles. Muscle activity was analyzed using wavelet analysis and examined within four sub-phases of the hop test, as well as an average of the task as …

Identification Of A Novel Microdeletion Causative Of Nance-Horan Syndrome, Kavya Rao

Faculty, Staff and Student Publications

BACKGROUND: Nance-Horan syndrome (NHS) is a rare X-linked genetic disorder characterized by ophthalmologic and dental anomalies as well as dysmorphic facies. The clinical phenotype in males includes congenital cataracts, vision loss, microcornea, nystagmus, microphthalmia, glaucoma, screwdriver blade-shaped incisors, supernumerary maxillary incisors, diastema, delays, intellectual disability, and dysmorphic facies. With the evolution of array-CGH technology, a total of five kindreds with NHS have been reported in the medical literature with microdeletions encompassing the NHS gene rather than sequencing variants.

METHODS: The patient is a 19-year-old male born to non-consanguineous parents with a past medical history of bilateral congenital cataracts, nystagmus, poor …

Genetic Subtyping And Phenotypic Characterization Of The Immune Microenvironment And Myc/Bcl2 Double Expression Reveal Heterogeneity In Diffuse Large B-Cell Lymphoma, Qingyan Au, Harry Nunns, Máté Nagy, Alexandar Tzankov, Feng Zhu, Carlo Visco, Govind Bhagat, Karen Dybkaer, April Chiu, Wayne Tam, Youli Zu, Eric D Hsi, Fredrick B Hagemeister, Xiaoping Sun, Xin Han, Heounjeong Go, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Benjamin M Parsons, J Han Van Krieken, Miguel A Piris, Jane N Winter, Yong Li, Bing Xu, Maher Albitar, Hua You, Ken H Young

Faculty, Staff and Students Publications

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is molecularly and clinically heterogeneous, and can be subtyped according to genetic alterations, cell-of-origin, or microenvironmental signatures using high-throughput genomic data at the DNA or RNA level. Although high-throughput proteomic profiling has not been available for DLBCL subtyping, MYC/BCL2 protein double expression (DE) is an established prognostic biomarker in DLBCL. The purpose of this study is to reveal the relative prognostic roles of DLBCL genetic, phenotypic, and microenvironmental biomarkers.

EXPERIMENTAL DESIGN: We performed targeted next-generation sequencing; IHC for MYC, BCL2, and FN1; and fluorescent multiplex IHC for microenvironmental markers in a large cohort of …

Subtype-Specific And Co-Occurring Genetic Alterations In B-Cell Non-Hodgkin Lymphoma, Man Chun John Ma, Saber Tadros, Alyssa Bouska, Tayla Heavican, Haopeng Yang, Dalia Moore, Keenan Hartert, Neeraj Jain, Jordan Showell, Sreejoyee Ghosh, Lesley Street, Marta Davidson, Christopher Carey, Joshua Tobin, Deepak Perumal, Julie M Vose, Matthew A Lunning, Aliyah R Sohani, Benjamin J Chen, Shannon Buckley, Loretta J Nastoupil, R Eric Davis, Jason R Westin, Nathan H Fowler, Samir Parekh, Maher Gandhi, Sattva Neelapu, Douglas Stewart, Kapil Bhalla, Javeed Iqbal, Timothy Greiner, Scott J Rodig, Adnan Mansoor, Michael R Green

Faculty, Staff and Student Publications

B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL, such as diffuse large B-cell lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, such as mantle cell lymphoma, remain less extensively characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth, including diffuse large B-cell lymphoma, …

Naked (N) Mutant Mice Carry A Nonsense Mutation In The Homeobox Of Hoxc13, Carlos J Perez, Lars Mecklenburg, Almudena Fernandez, Marta Cantero, Tiago Antonio De Souza, Sharon Y R Dent, Alexander Awgulewitsch, Fernando Benavides

Faculty, Staff and Student Publications

Loss of function mutations in HOXC13 have been associated with Ectodermal Dysplasia-9, Hair/Nail Type (ECTD9) in consanguineous families, characterized by sparse to complete absence of hair and nail dystrophy. Here we characterize the spontaneous mouse mutation Naked (N) as a terminal truncation in the Hoxc13 (homeobox C13) gene. Similar to previous reports for homozygous Hoxc13 knock-out (KO) mice, homozygous N/N mice exhibit generalized alopecia with abnormal nails and a short lifespan. However, in contrast to Hoxc13 heterozygous KO mice, N/+ mice show generalized or partial alopecia, associated with loss of hair fibres, along with normal lifespan and fertility. Our data …

Fungi: Friend Or Foe? A Mycobiome Evaluation In Children With Autism And Gastrointestinal Symptoms, Manouchehr Hessabi, Deborah A Pearson, Rosleen Mansour, Melissa R Van Arsdall, Fernando Navarro, J Marc Rhoads

Faculty, Staff and Student Publications

Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and …

Kaposiform Lymphangiomatosis Presenting With A Group A Streptococcus Pericardial Effusion

Faculty, Staff and Student Publications

A 4-year-old child was transferred to the paediatric intensive care unit with acute respiratory failure following 4 days of fever, nausea and vomiting. Chest X-ray on admission had an enlarged cardiac silhouette and transthoracic echo confirmed a large pericardial effusion. An emergent pericardiocentesis was performed at bedside which drained nearly 1000 mL of purulent fluid. Postdrainage course was complicated by acute systolic and diastolic heart failure, thrombocytopenia and acute renal failure. A chest CT and MRI were concerning for a diffuse mediastinal soft-tissue density, so the patient underwent interventional radiology-guided biopsy complicated by haemorrhage requiring mediastinal exploration and subtotal thymectomy. …

Underutilization Of Endovascular Therapy In Black Patients With Ischemic Stroke: An Analysis Of State And Nationwide Cohorts, Rania Abdelkhaleq

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Endovascular therapy (EVT) is a very effective treatment but relies on specialized capabilities that are not available in every hospital where acute ischemic stroke is treated. Here, we assess whether access to and utilization of this therapy has extended uniformly across racial and ethnic groups.

METHODS: We conducted a retrospective, population-based study using the 2019 Texas Inpatient Public Use Data File. Acute ischemic stroke cases and EVT use were identified using the

RESULTS: Among 40 814 acute ischemic stroke cases in Texas in 2019, 54% were White, 17% Black, and 21% Hispanic. Black patients had similar admissions …

Artificial Intelligence And Chatbots In Psychiatry

Faculty, Staff and Student Publications

The utilization of artificial intelligence (AI) in psychiatry has risen over the past several years to meet the growing need for improved access to mental health solutions. Additionally, shortages of mental health providers during the COVID-19 pandemic have continued to exacerbate the burden of mental illness worldwide. AI applications already in existence include those enabled to assist with psychiatric diagnoses, symptom tracking, disease course prediction, and psychoeducation. Modalities of AI mental health care delivery include availability through the internet, smartphone applications, and digital gaming. Here we review emerging AI-based interventions in the form of chat and therapy bots, specifically conversational …

Radiation Doses In Patients Undergoing Computed Tomographic Coronary Artery Calcium Evaluation With A 64-Slice Scanner Versus A 256-Slice Scanner, Paul Madaj, Dong Li, Rine Nakanishi, Daniele Andreini, Gianluca Pontone, Edoardo Conte, Rachael O'Rourke, Christian Hamilton-Craig, Manojna Nimmagadda, Nicholas Kim, Badiha Fatima, Christopher Dailing, Kashif Shaikh, Chandana Shekar, Ju Hwan Lee, Matthew J Budoff

The Texas Heart Institute Journal

Computed tomographic coronary artery calcium scanning enables cardiovascular risk stratification; however, exposing patients to high radiation levels is an ongoing concern. New-generation computed tomographic systems use lower radiation doses than older systems do. To quantify comparative doses of radiation exposure, we prospectively acquired images from 220 patients with use of a 64-slice GE LightSpeed VCT scanner (control group, n=110) and a 256-slice GE Revolution scanner (study group, n=110). The groups were matched for age, sex, and body mass index; statistical analysis included t tests and linear regression.

The mean dose-length product was 21% lower in the study group than in …

The Europdx Data Portal: An Open Platform For Patient-Derived Cancer Xenograft Data Sharing And Visualization., Zdenka Dudová, Nathalie Conte, Jeremy Mason, Dalibor Stuchlík, Radim Peša, Csaba Halmagyi, Zinaida Perova, Abayomi Mosaku, Ross Thorne, Alex Follette, Ľuboslav Pivarč, Radim Šašinka, Muhammad Usman, Steven Neuhauser, Dale A. Begley, Debra M Krupke, Massimiliano Frassà, Alessandro Fiori, Riccardo Corsi, Luca Vezzadini, Claudio Isella, Andrea Bertotti, Carol J Bult, Helen Parkinson, Enzo Medico, Terrence Meehan, Aleš Křenek

Faculty Research 2022

BACKGROUND: Patient-derived xenografts (PDX) mice models play an important role in preclinical trials and personalized medicine. Sharing data on the models is highly valuable for numerous reasons - ethical, economical, research cross validation etc. The EurOPDX Consortium was established 8 years ago to share such information and avoid duplicating efforts in developing new PDX mice models and unify approaches to support preclinical research. EurOPDX Data Portal is the unified data sharing platform adopted by the Consortium.

MAIN BODY: In this paper we describe the main features of the EurOPDX Data Portal ( https://dataportal.europdx.eu/ ), its architecture and possible utilization by …

Care Team And Practice-Level Implementation Strategies To Optimize Pediatric Collaborative Care: Study Protocol For A Cluster-Randomized Hybrid Type Iii Trial, David J Kolko, Elizabeth A Mcguier, Renee Turchi, Eileen Thompson, Satish Iyengar, Shawna N Smith, Kimberly Hoagwood, Celeste Liebrecht, Ian M Bennett, Byron J Powell, Kelly Kelleher, Maria Silva, Amy M Kilbourne

2020-Current year OA Pubs

BACKGROUND: Implementation facilitation is an effective strategy to support the implementation of evidence-based practices (EBPs), but our understanding of multilevel strategies and the mechanisms of change within the "black box" of implementation facilitation is limited. This implementation trial seeks to disentangle and evaluate the effects of facilitation strategies that separately target the care team and leadership levels on implementation of a collaborative care model in pediatric primary care. Strategies targeting the provider care team (TEAM) should engage team-level mechanisms, and strategies targeting leaders (LEAD) should engage organizational mechanisms.

METHODS: We will conduct a hybrid type 3 effectiveness-implementation trial in a …

Safety And Activity Of Pembrolizumab In Combination With Rituximab In Relapsed Or Refractory Follicular Lymphoma, Loretta J Nastoupil, Collin K Chin, Jason R Westin, Nathan H Fowler, Felipe Samaniego, Man Chun John Ma, Fuliang Chu, Ly Dsouza, Chizobam Obi, Jennifer Mims, Lei Feng, Shouhao Zhou, Michael Green, Richard Eric Davis, Sattva S Neelapu

Faculty, Staff and Student Publications

PD-1 blockade enhances the function of antitumor T cells and antibody-dependent, cell-mediated cytotoxicity (ADCC) of NK cells. In a single-center, open-label, phase 2 trial, we tested the combination of pembrolizumab, an anti-PD-1 monoclonal antibody, and rituximab, an anti-CD20 monoclonal antibody that induces ADCC, in 30 patients with follicular lymphoma (FL) with rituximab-sensitive disease who had relapsed after ≥1 prior therapy. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 16 cycles, and rituximab was given at 375 mg/m2 IV weekly for 4 weeks in cycle 1 only. The most common grade 3/4 adverse events (AEs) were …

The Influence Of Preoperative Dialysis On Survival After Continuous-Flow Left Ventricular Assist Device Implantation, Ajith P Nair, Andrew B Civitello, Leo Simpson, O H Frazier, George V Letsou

Faculty, Staff and Students Publications

OBJECTIVES: Dialysis is considered a contraindication to continuous-flow left ventricular assist device (CF-LVAD) implantation. We evaluated clinical outcomes and survival in carefully selected, low-risk patients with renal failure who required dialysis before CF-LVAD implantation.

METHODS: We extracted medical record data of patients who underwent CF-LVAD placement at our centre between 1 January 2006 and 31 August 2017, with 2 clinical scenarios: those who required long-term (>14 days) dialysis and those who required short-term (≤14 days) dialysis immediately before implantation. Demographic, clinical and intraoperative characteristics and survival outcomes were assessed.

RESULTS: Of 621 patients who underwent CF-LVAD implantation during the …

Transitions Of Care: Completeness Of The Interoperability Data Standard For Communication From Home Health Care To Primary Care., Edgar Chou, Paulina S Sockolow

Department of Medicine Faculty Papers

Data sharing is necessary to address communication deficits along the transitions of care among community settings. Evidence-based practice supports home healthcare (HHC) patients to see their primary care team within the first two weeks of hospital discharge to reduce rehospitalization risk. A small subset of patient data collected at HHC admission is mandated to be transmitted to primary care, predominantly by fax. Using qualitative analysis, we assessed completeness of the United States Core Data for Interoperability (USCDI) interoperability standard, as compared to the patient data collected by the primary care team (topics) and HHC (classes) during the initial visit; and …

Activation Of Ras/Mapk Pathway Confers Mcl-1 Mediated Acquired Resistance To Bcl-2 Inhibitor Venetoclax In Acute Myeloid Leukemia, Qi Zhang, Bridget Riley-Gillis, Lina Han, Yannan Jia, Alessia Lodi, Saravanan Ganesan, Sergej N Konoplev, Shannon R Sweeney, Jeremy A Ryan, Yulia Jitkova, Kenneth Dunner, Shaun E Grosskurth, Priyanka Vijay, Sujana Ghosh, Charles Lu, Wencai Ma, Stephen Kurtz, Vivian R Ruvolo, Helen Ma, Connie C Weng, Cassandra L Ramage, Natalia Baran, Ce Shi, Tianyu Cai, Richard Eric Davis, Venkata L Battula, Yingchang Mi, Jing Wang, Courtney D Dinardo, Michael Andreeff, Jeffery W Tyner, Aaron Schimmer, Anthony Letai, Rose Ann Padua, Carlos E Bueso-Ramos, Stefano Tiziani, Joel Leverson, Relja Popovic, Marina Konopleva

Faculty, Staff and Student Publications

Despite high initial response rates, acute myeloid leukemia (AML) treated with the BCL-2-selective inhibitor venetoclax (VEN) alone or in combinations commonly acquires resistance. We performed gene/protein expression, metabolomic and methylation analyses of isogenic AML cell lines sensitive or resistant to VEN, and identified the activation of RAS/MAPK pathway, leading to increased stability and higher levels of MCL-1 protein, as a major acquired mechanism of VEN resistance. MCL-1 sustained survival and maintained mitochondrial respiration in VEN-RE cells, which had impaired electron transport chain (ETC) complex II activity, and MCL-1 silencing or pharmacologic inhibition restored VEN sensitivity. In support of the importance …

Artificial Intelligence In Mammographic Phenotyping Of Breast Cancer Risk: A Narrative Review, Aimilia Gastounioti, Shyam Desai, Vinayak S Ahluwalia, Emily F Conant, Despina Kontos

2020-Current year OA Pubs

BACKGROUND: Improved breast cancer risk assessment models are needed to enable personalized screening strategies that achieve better harm-to-benefit ratio based on earlier detection and better breast cancer outcomes than existing screening guidelines. Computational mammographic phenotypes have demonstrated a promising role in breast cancer risk prediction. With the recent exponential growth of computational efficiency, the artificial intelligence (AI) revolution, driven by the introduction of deep learning, has expanded the utility of imaging in predictive models. Consequently, AI-based imaging-derived data has led to some of the most promising tools for precision breast cancer screening.

MAIN BODY: This review aims to synthesize the …

Mild Encephalitis/Encephalopathy With A Reversible Splenial Lesion Associated With Systemic Mycoplasma Pneumoniae Infection In North America: A Case Report

Faculty, Staff and Student Publications

BACKGROUND: Mild encephalitis/encephalopathy with reversible splenial lesion is a clinical-radiological entity found to occur in the setting of an acute systemic inflammatory state with isolated lesions of the splenium of the corpus callosum and mild encephalopathy. Mild encephalitis/encephalopathy with reversible splenial lesion is commonly found to occur in children in the setting of viral infections. It has rarely been associated with Mycoplasma pneumoniae in the United States, unlike in Eastern and Southern Asia where this is much more prominent.

CASE PRESENTATIONS: A 5-year-old African-American boy with autism spectrum disorder presented to our emergency department with acute onset intractable vomiting, diarrhea, …

Rare Coding Variants In Rcn3 Are Associated With Blood Pressure, Karen Y. He, Tanika N. Kelly, Heming Wang, Jingjing Liang, Luke Zhu, Brian E. Cade, Themistocles L. Assimes, Lewis C. Becker, Amber L. Beitelshees, Lawrence F. Bielak, Adam P. Bress, Jennifer A. Brody, Yen-Pei Christy Chang, Yi-Cheng Chang, Paul S. De Vries, Ravindranath Duggirala, Ervin R. Fox, Nora Franceschini, Anna L. Furniss, Yan Gao, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of …

The Social Cerebellum: A Large-Scale Investigation Of Functional And Structural Specificity And Connectivity, Athanasia Metoki, Yin Wang, Ingrid R Olson

2020-Current year OA Pubs

The cerebellum has been traditionally disregarded in relation to nonmotor functions, but recent findings indicate it may be involved in language, affective processing, and social functions. Mentalizing, or Theory of Mind (ToM), is the ability to infer mental states of others and this skill relies on a distributed network of brain regions. Here, we leveraged large-scale multimodal neuroimaging data to elucidate the structural and functional role of the cerebellum in mentalizing. We used functional activations to determine whether the cerebellum has a domain-general or domain-specific functional role, and effective connectivity and probabilistic tractography to map the cerebello-cerebral mentalizing network. We …

Crare Coding Variants In Rcn3 Are Associated With Blood Pressure, Luke Zhu, Lewis C Becker, Amber L Beitelshees, Lawrence F Bielak, Adam P Bress, Jennifer A Brody, Yen-Pei Christy Chang, Yi-Cheng Chang, Paul S De Vries, Ravindranath Duggirala, Ervin R Fox, Nora Franceschini, Anna L Furniss, Yan Gao, Xiuqing Guo, Jeffrey Haessler, Yi-Jen Hung, Shih-Jen Hwang, Rita R Kalyani, Ching-Ti Liu, Chunyu Liu, Lisa Warsinger Martin, May E Montasser, Paul M Muntner, Stanford Mwasongwe, Take Naseri, Walter Palmas, Muagututi'a Sefuiva Reupena, Kenneth M Rice, Wayne H-H Sheu, Daichi Shimbo, Jennifer A Smith, Beverly M Snively, Lisa R Yanek, Wei Zhao, John Blangero, Eric Boerwinkle, Yii-Der Ida Chen, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, Myriam Fornage, Jiang He, Lifang Hou, Robert C Kaplan, Sharon L R Kardia, Eimear E Kenny, Charles Kooperberg, Donald Lloyd-Jones, Ruth J F Loos, Rasika A Mathias, Stephen T Mcgarvey, Braxton D Mitchell, Kari E North, Patricia A Peyser, Bruce M Psaty, Laura M Raffield, D C Rao, Susan Redline, Alex P Reiner, Stephen S Rich, Jerome I Rotter, Kent D Taylor, Russell Tracy, Ramachandran S Vasan, Samoan Obesity, Lifestyle And Genetic Adaptations Study (Olaga) Group, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Alanna C Morrison, Daniel Levy, Aravinda Chakravarti, Donna K Arnett, Xiaofeng Zhu

Faculty, Staff and Student Publications

BACKGROUND: While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of …

Dietary Patterns Are Associated With Improved Ovarian Reserve In Overweight And Obese Women: A Cross-Sectional Study Of The Lifestyle And Ovarian Reserve (Lore) Cohort, Ashley M Eskew, Bronwyn S Bedrick, Jorge E Chavarro, Joan K Riley, Emily S Jungheim

2020-Current year OA Pubs

BACKGROUND: Growing evidence suggests that adherence to certain dietary patterns is associated with improved fecundity and reproductive outcomes in the general population and infertile couples assisted reproductive treatments. The objective of this study was to assess if dietary patterns are associated with ovarian reserve in reproductive age women without a history of infertility.

METHODS: This was a cross-sectional study of 185 women in the Lifestyle and Ovarian Reserve (LORe) cohort. Women aged 18-44 without a history of infertility were recruited from the local community at an academic medical center. Subjects completed validated food frequency and physical activity questionnaires to assess …