Digital Commons Network^™

Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation In Preterm Pigs, Line I Christiansen, Bo Holmqvist, Xiaoyu Pan, Kristine Holgersen, Sandy E H Lindholm, Nicole L Henriksen, Douglas G Burrin, David Ley, Thomas Thymann, Per Torp Sangild, Stanislava Pankratova

Faculty, Staff and Students Publications

Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurodevelopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investigated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development. Pigs were treated with 2.25 mg/kg/d recombinant human IGF-1/IGF binding protein-3 complex from birth until day 5 or 9 before the collection of brain samples for quantitative immunohistochemistry (IHC), RNA sequencing, and quantitative PCR analyses. Brain protein synthesis was …

A Learned Map For Places And Concepts In The Human Medial Temporal Lobe, Nora A. Herweg, Lukas Kunz, Daniel Schonhaut, Armin Brandt, Paul A. Wanda, Ashwini D. Sharan, Michael R. Sperling, Andreas Schulze-Bonhage, Michael J. Kahana

Department of Neurology Faculty Papers

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL microwire recordings from 20 patients (9 female, 11 male) navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings. The array of local field potentials in the MTL contains sufficient information …

Hpv-Related Anal Cancer Is Associated With Changes In The Anorectal Microbiome During Cancer Development, Jacob H Elnaggar, Victoria O Huynh, Daniel Lin, R Tyler Hillman, Chike O Abana, Molly B El Alam, Katarina C Tomasic, Tatiana V Karpinets, Ramez Kouzy, Jae L Phan, Jennifer Wargo, Emma B Holliday, Prajnan Das, Melissa P Mezzari, Nadim J Ajami, Erica J Lynn, Bruce D Minsky, Van K Morris, Andrea Milbourne, Craig A Messick, Ann H Klopp, P Andrew Futreal, Cullen M Taniguchi, Kathleen M Schmeler, Lauren E Colbert

Faculty, Staff and Student Publications

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease.

METHODS: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade …

Spontaneous Activity Patterns In Human Attention Networks Code For Hand Movements, Lu Zhang, Lorenzo Pini, Dohyun Kim, Gordon L Shulman, Maurizio Corbetta

2020-Current year OA Pubs

Recent evidence suggests that, in the absence of any task, spontaneous brain activity patterns and connectivity in the visual and motor cortex code for natural stimuli and actions, respectively. These "resting-state" activity patterns may underlie the maintenance and consolidation (replay) of information states coding for ecological stimuli and behaviors. In this study, we examine whether replay patterns occur in resting-state activity in association cortex grouped into high-order cognitive networks not directly processing sensory inputs or motor outputs. Fifteen participants (7 females) performed four hand movements during an fMRI study. Three movements were ecological. The fourth movement as control was less …

Neuronal Sirt3 Deletion Predisposes To Female-Specific Alterations In Cellular Metabolism, Memory, And Network Excitability, Jennifer N Pearson-Smith, Ruth Fulton, Christopher Q Huynh, Anna G Figueroa, Gia B Huynh, Li-Ping Liang, Lindsey B Gano, Cole R Michel, Nichole Reisdorph, Richard Reisdorph, Kristofer S Fritz, Eric Verdin, Manisha Patel

Faculty, Staff and Students Publications

Mitochondrial dysfunction is an early event in the pathogenesis of neurologic disorders and aging. Sirtuin 3 (SIRT3) regulates mitochondrial function in response to the cellular environment through the reversible deacetylation of proteins involved in metabolism and reactive oxygen species detoxification. As the primary mitochondrial deacetylase, germline, or peripheral tissue-specific deletion of SIRT3 produces mitochondrial hyperacetylation and the accelerated development of age-related diseases. Given the unique metabolic demands of neurons, the role of SIRT3 in the brain is only beginning to emerge. Using mass spectrometry-based acetylomics, high-resolution respirometry, video-EEG, and cognition testing, we report targeted deletion of SIRT3 from select neurons …

Ideal Cardiovascular Health, Biomarkers, And Coronary Artery Disease In Persons With Hiv, Pamela S Douglas, Sara Mccallum, Michael T Lu, Triin Umbleja, Kathleen V Fitch, Borek Foldyna, Markella V Zanni, Evelynne S Fulda, Gerald S Bloomfield, Carl J Fichtenbaum, Edgar T Overton, Judith A Aberg, Carlos D Malvestutto, Tricia H Burdo, Roberto C Arduino, Ken S Ho, Michael T Yin, Heather J Ribaudo, Steven K Grinspoon

Faculty, Staff and Student Publications

OBJECTIVE: To investigate relationships between Life's Simple 7 (LS7), an assessment of cardiovascular health (CVH), and coronary plaque among people with HIV (PWH).

DESIGN: Cross-sectional.

METHODS: Coronary computed tomography angiography, immune/inflammatory biomarkers, and characterization of LS7 were collected among a subset of ART-treated PWH enrolled in REPRIEVE, a primary prevention trial. Analyses adjusted for cardiovascular disease risk (ASCVD score).

RESULTS: Median age of the 735 participants was 51(±6) years, 16% female, and median (Q1-Q3) CVD risk was 4.5% (2.6-6.9). Forty percent had poor (≤2 ideal components), 51% had intermediate (three or four ideal components), and only 9% had ideal CVH …

Predicting Locations Of Cryptic Pockets From Single Protein Structures Using The Pocketminer Graph Neural Network, Artur Meller, Michael Ward, Jonathan Borowsky, Meghana Kshirsagar, Jeffrey M Lotthammer, Felipe Oviedo, Juan Lavista Ferres, Gregory R Bowman

2020-Current year OA Pubs

Cryptic pockets expand the scope of drug discovery by enabling targeting of proteins currently considered undruggable because they lack pockets in their ground state structures. However, identifying cryptic pockets is labor-intensive and slow. The ability to accurately and rapidly predict if and where cryptic pockets are likely to form from a structure would greatly accelerate the search for druggable pockets. Here, we present PocketMiner, a graph neural network trained to predict where pockets are likely to open in molecular dynamics simulations. Applying PocketMiner to single structures from a newly curated dataset of 39 experimentally confirmed cryptic pockets demonstrates that it …

Cnih3 Deletion Dysregulates Dorsal Hippocampal Transcription Across The Estrous Cycle, Bernard Mulvey, Hannah E. Frye, Tania Lintz, Stuart Fass, Eric Tycksen, Elliot C. Nelson, Jose A. Morón, Joseph D. Dougherty

2020-Current year OA Pubs

In females, the hippocampus, a critical brain region for coordination of learning, memory, and behavior, displays altered physiology and behavioral output across the estrous or menstrual cycle. However, the molecular effectors and cell types underlying these observed cyclic changes have only been partially characterized to date. Recently, profiling of mice null for the AMPA receptor trafficking gene

Association Of Glucose-6-Phosphate Dehydrogenase Deficiency With Outcomes In Us Veterans With Covid-19, Sarah H Elsea, Javad Razjouyan, Kyung Min Lee, Julie A Lynch, Sharyl Martini, Lavannya M Pandit

Faculty, Staff and Students Publications

IMPORTANCE: The underlying biological risk factors for severe outcome due to SAR-CoV-2 infection are not well defined.

OBJECTIVE: To determine the association between glucose-6-phosphate dehydrogenase (G6PD) deficiency and severity of COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included analysis of 24 700 veterans with G6PD enzyme testing prior to January 1, 2020, obtained through the US Veterans Health Administration national databases. These veterans were cross-referenced with the Veterans Administration COVID-19 Shared Data Resource for SARS-CoV-2 testing from February 15, 2020, to January 1, 2021. The final study population consisted of 4811 veterans who tested positive for SARS-CoV-2. Statistical …

Types Of Diagnostic Errors Reported By Paediatric Emergency Providers In A Global Paediatric Emergency Care Research Network, Prashant Mahajan, Joseph A Grubenhoff, Jim Cranford, Maala Bhatt, James M Chamberlain, Todd Chang, Mark Lyttle, Rianne Oostenbrink, Damian Roland, Richard M Rudy, Kathy N Shaw, Robert Velasco Zuniga, Apoorva Belle, Nathan Kuppermann, Hardeep Singh

Faculty, Staff and Students Publications

Background: Diagnostic errors, reframed as missed opportunities for improving diagnosis (MOIDs), are poorly understood in the paediatric emergency department (ED) setting. We investigated the clinical experience, harm and contributing factors related to MOIDs reported by physicians working in paediatric EDs.

Methods: We developed a web-based survey in which physicians participating in the international Paediatric Emergency Research Network representing five out of six WHO regions, described examples of MOIDs involving their own or a colleague's patients. Respondents provided case summaries and answered questions regarding harm and factors contributing to the event.

Results: Of 1594 physicians surveyed, 412 (25.8%) responded (mean age=43 …

Crispr/Cas9 Screen Uncovers Functional Translation Of Cryptic Lncrna-Encoded Open Reading Frames In Human Cancer, Caishang Zheng, Yanjun Wei, Peng Zhang, Longyong Xu, Zhenzhen Zhang, Kangyu Lin, Jiakai Hou, Xiangdong Lv, Yao Ding, Yulun Chiu, Antrix Jain, Nelufa Islam, Anna Malovannaya, Yun Wu, Feng Ding, Han Xu, Ming Sun, Xi Chen, Yiwen Chen

Faculty, Staff and Students Publications

Emerging evidence suggests that cryptic translation within long noncoding RNAs (lncRNAs) may produce novel proteins with important developmental/physiological functions. However, the role of this cryptic translation in complex diseases (e.g., cancer) remains elusive. Here, we applied an integrative strategy combining ribosome profiling and CRISPR/Cas9 screening with large-scale analysis of molecular/clinical data for breast cancer (BC) and identified estrogen receptor α-positive (ER+) BC dependency on the cryptic ORFs encoded by lncRNA genes that were upregulated in luminal tumors. We confirmed the in vivo tumor-promoting function of an unannotated protein, GATA3-interacting cryptic protein (GT3-INCP) encoded by LINC00992, the expression of which was …

In Utero Exposure To Antiemetic And Risk Of Adult-Onset Colorectal Cancer, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as risk factors. Dicyclomine, an antispasmodic used to treat irritable bowel syndrome, was initially included in Bendectin (comprising doxylamine, pyridoxine, and dicyclomine), an antiemetic prescribed during pregnancy in the 1960s.

METHODS: We estimated the association between in utero exposure to Bendectin and risk of CRC in offspring of the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in Oakland, CA, between 1959 and 1966 (n = 14 507 mothers and 18 751 …

In Vivo White Matter Microstructure In Adolescents With Early-Onset Psychosis: A Multi-Site Mega-Analysis, Claudia Barth, Sinead Kelly, Stener Nerland, Neda Jahanshad, Clara Alloza, Sonia Ambrogi, Ole A Andreassen, Dimitrios Andreou, Celso Arango, Inmaculada Baeza, Nerisa Banaj, Carrie E Bearden, Michael Berk, Hannes Bohman, Josefina Castro-Fornieles, Yann Chye, Benedicto Crespo-Facorro, Elena De La Serna, Covadonga M Díaz-Caneja, Tiril P Gurholt, Catherine E Hegarty, Anthony James, Joost Janssen, Cecilie Johannessen, Erik G Jönsson, Katherine H Karlsgodt, Peter Kochunov, Noemi G Lois, Mathias Lundberg, Anne M Myhre, Saül Pascual-Diaz, Fabrizio Piras, Runar E Smelror, Gianfranco Spalletta, Therese S Stokkan, Gisela Sugranyes, Chao Suo, Sophia I Thomopoulos, Diana Tordesillas-Gutiérrez, Daniela Vecchio, Kirsten Wedervang-Resell, Laura A Wortinger, Paul M Thompson, Ingrid Agartz

Faculty, Staff and Students Publications

Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 >years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age = 16.6 years, interquartile range (IQR) = 2.14, 46.4% females) and 265 adolescent healthy controls (median age = 16.2 years, IQR = 2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean …

Brain Ageing In Schizophrenia: Evidence From 26 International Cohorts Via The Enigma Schizophrenia Consortium, Constantinos Constantinides, Laura K M Han, Clara Alloza, Linda Antonella Antonucci, Celso Arango, Rosa Ayesa-Arriola, Nerisa Banaj, Alessandro Bertolino, Stefan Borgwardt, Jason Bruggemann, Juan Bustillo, Oleg Bykhovski, Vince Calhoun, Vaughan Carr, Stanley Catts, Young-Chul Chung, Benedicto Crespo-Facorro, Covadonga M Díaz-Caneja, Gary Donohoe, Stefan Du Plessis, Jesse Edmond, Stefan Ehrlich, Robin Emsley, Lisa T Eyler, Paola Fuentes-Claramonte, Foivos Georgiadis, Melissa Green, Amalia Guerrero-Pedraza, Minji Ha, Tim Hahn, Frans A Henskens, Laurena Holleran, Stephanie Homan, Philipp Homan, Neda Jahanshad, Joost Janssen, Ellen Ji, Stefan Kaiser, Vasily Kaleda, Minah Kim, Woo-Sung Kim, Matthias Kirschner, Peter Kochunov, Yoo Bin Kwak, Jun Soo Kwon, Irina Lebedeva, Jingyu Liu, Patricia Mitchie, Stijn Michielse, David Mothersill, Bryan Mowry, Víctor Ortiz-García De La Foz, Christos Pantelis, Giulio Pergola, Fabrizio Piras, Edith Pomarol-Clotet, Adrian Preda, Yann Quidé, Paul E Rasser, Kelly Rootes-Murdy, Raymond Salvador, Marina Sangiuliano, Salvador Sarró, Ulrich Schall, André Schmidt, Rodney J Scott, Pierluigi Selvaggi, Kang Sim, Antonin Skoch, Gianfranco Spalletta, Filip Spaniel, Sophia I Thomopoulos, David Tomecek, Alexander S Tomyshev, Diana Tordesillas-Gutiérrez, Therese Van Amelsvoort, Javier Vázquez-Bourgon, Daniela Vecchio, Aristotle Voineskos, Cynthia S Weickert, Thomas Weickert, Paul M Thompson, Lianne Schmaal, Theo G M Van Erp, Jessica Turner, James H Cole, Enigma Schizophrenia Consortium, Danai Dima, Esther Walton

Faculty, Staff and Students Publications

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18–72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18–73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on …

Use Of Contrast Media During Ct-Guided Thermal Ablation Of Colorectal Liver Metastasis For Procedure Planning Is Associated With Improved Immediate Outcomes, Iwan Paolucci, Yuan-Mao Lin, A Kyle Jones, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

PURPOSE: The aim of this study was to analyze the impact of using intra-procedural pre-ablation contrast-enhanced CT prior to percutaneous thermal ablation (pre-ablation CECT) of colorectal liver metastases (CLM) on local outcomes.

MATERIALS AND METHODS: This retrospective analysis of a prospectively collected liver ablation registry included 144 consecutive patients (median age 57 years IQR [49, 65], 60% men) who underwent 173 CT-guided ablation sessions for 250 CLM between October 2015 and March 2020. In addition to oncologic outcomes, technical success was retrospectively evaluated using a biomechanical deformable image registration software for 3D-minimal ablative margin (3D-MAM) quantification. Bayesian regression was used …

Transabdominal Cerclage During Pregnancy: A Retrospective Single Operator Series Over A Quarter Century, David R Hall, Mari Van De Vyver

Faculty, Staff and Student Publications

OBJECTIVE: To describe the pregnancy outcomes and complications observed in a series of cases of transabdominal cerclage (TAC), which is reserved for highly selected women with recurrent mid-trimester pregnancy loss, due to cervical insufficiency.

METHODS: A retrospective audit covering 25 years (January 1, 1997 to December 31, 2021) was performed at the Obstetric Special Care division, Tygerberg Academic Hospital in Cape Town, South Africa. All 118 pregnancies from 94 procedures, operated and managed by the principal author were included for descriptive analysis.

RESULTS: Eighty-four (91.3%) of the 92 first pregnancies after first insertion had successful outcomes. All second and third …

Linoleic Acid Improves Piezo2 Dysfunction In A Mouse Model Of Angelman Syndrome, Luis O Romero, Rebeca Caires, A Kaitlyn Victor, Juanma Ramirez, Francisco J Sierra-Valdez, Patrick Walsh, Vincent Truong, Jungsoo Lee, Ugo Mayor, Lawrence T Reiter, Valeria Vásquez, Julio F Cordero-Morales

Faculty, Staff and Student Publications

Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability and atypical behaviors. AS results from loss of expression of the E3 ubiquitin-protein ligase UBE3A from the maternal allele in neurons. Individuals with AS display impaired coordination, poor balance, and gait ataxia. PIEZO2 is a mechanosensitive ion channel essential for coordination and balance. Here, we report that PIEZO2 activity is reduced in Ube3a deficient male and female mouse sensory neurons, a human Merkel cell carcinoma cell line and female human iPSC-derived sensory neurons with UBE3A knock-down, and de-identified stem cell-derived neurons from individuals with AS. We find that loss …

Heterotopic Pregnancy: A Difficult And Rarely Considered Diagnosis., Joseph M Crum, Howard W Levitin

Women’s Health Articles

A 34-year-old pregnant female presented to the emergency department (ED) with complaints of abdominal pain and vaginal bleeding for two days. The day prior, she was evaluated by her obstetrician and gynecologist with a transvaginal ultrasound demonstrating an intrauterine pregnancy at approximately six weeks gestation. After treatment of symptoms and reassuring laboratory testing, she went home. However, she returned two days later with worsening complaints. It was discovered that the patient had a heterotopic pregnancy, or a concomitant intrauterine and extrauterine pregnancy, resulting from natural conception in the absence of identifiable risk factors. While exceedingly rare, this diagnosis is frequently …

Electrophysiological Normative Responses To Emotional, Neutral, And Cigarette-Related Images, Francesco Versace, Nicola Sambuco, Menton M Deweese, Paul M Cinciripini

Faculty, Staff and Student Publications

To create reproducible emotional probes, affective scientists rely on sets of standardized pictures that are normed using subjective ratings of valence and emotional arousal. However, when emotional responses are investigated using neurophysiological measures, it might be more appropriate to select pictures integrating information from normative subjective reports and normative neurophysiological responses. Here, we provide electrophysiological normative responses for 323 emotional pictures (215 from the IAPS) covering a wide range of categories (erotica, romantic, appetizing foods, landscapes, people engaged in mundane activities, household objects, disgusting objects, accidents, sad people, violence, mutilations, and cigarette-related contents). Event-related potentials (ERPs) and subjective ratings of …

Sleep Duration, Hypnotic Drug Use, And Risk Factors: Cross- Sectional Study, Nazanin Jalali, Parvin Khalili, Zahra Jamali, Zahra Jalali, Amir Moghadam-Ahmadi, Alireza Vakilian, Fatemeh Ayoobi

Department of Neurology Faculty Papers

Both short sleep duration (SSD) and long sleep duration (LSD) are associated with an increased risk of morbidity and mortality. Here, we aimed to assess the prevalence of sleep duration disturbances among adults in association with demographic, medication use, personal habits, and chronic diseases, while also considering the impact of hypnotic drug use. We performed a cross-sectional study of 9991 adult participants of the Rafsanjan Cohort Study (RCS), as part of the Prospective epidemiological research studies in Iran (PERSIAN). Multivariate logistic regression analyses were conducted to assess the association between short (< 6 h) and long (> 9 h) sleep duration with demographic and lifestyle …

Child Abuse Pediatrics Research Network: The Capnet Core Data Project, Joanne N Wood, Kristine A Campbell, James D Anderst, Angela N Bachim, Rachel P Berger, Kent P Hymel, Nancy S Harper, Megan M Letson, John D Melville, Oluwatimilehin Okunowo, Daniel M Lindberg

Faculty, Staff and Students Publications

OBJECTIVE: Examine the epidemiology of subspecialty physical abuse evaluations within CAPNET, a multicenter child abuse pediatrics research network.

METHODS: We conducted a cross-sectional study of children(in-person or remote) by a child abuse pediatrician (CAP) due to concerns for physical abuse at ten CAPNET hospital systems from February 2021 through December 2021.

RESULTS: Among 3667 patients with 3721 encounters, 69.4% wereold; 44.3%old, 59.1% male; 27.1% Black; 57.8% White, 17.0% Hispanic; and 71.0 % had public insurance. The highest level of care was outpatient/emergency department in 60.7%, inpatient unit in 28.0% and intensive care in 11.4%. CAPs performed 79.1% in-person consultations and …

Body Mass Index And Molecular Subtypes Of Colorectal Cancer, Neil Murphy, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease.

METHODS: We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables.

RESULTS: Higher BMI was associated with increased CRC risk (OR per 5 kg/m2 = 1.18, 95% CI = …

The Relationship Of Social Determinants And Distress In Newly Diagnosed Cancer Patients, Brandon Okeke, Cheron Hillmon, Jasmine Jones, Grace Obanigba, Ann Obi, Meagan Nkansah, Nicholas Odiase, Kamil Khanipov, Ikenna C. Okereke

Surgery Articles

Patients with a new cancer diagnosis can experience distress when diagnosed. There are disparities in treatment of cancer patients based on social determinants, but minimal research exists on the relationship of those social determinants and distress after a new cancer diagnosis. Our goals were to determine the social determinants associated with distress after a new cancer diagnosis and determine the relationship of distress with outcome. Patients with a new cancer diagnosis at one institution from January 2019 to December 2020 were analyzed. Patients were given the National Comprehensive Cancer Network (NCCN) distress thermometer during their first visit. Demographics, tumor characteristics, …

Patient-Reported Symptoms At Discharge And Risk Of Complications After Gynecologic Surgery, Xin Shelley Wang, Pedro T Ramirez, Qiuling Shi, Mona Kamal, Araceli Garcia-Gonzalez, Maria D Iniesta, Charles S Cleeland, Larissa A Meyer

Faculty, Staff and Student Publications

Objective: Current gaps in knowledge limit clinicians from fully implementing patient-reported outcomes in routine post-operative care.

Methods: This prospective study assessed symptoms via the gynecologic module of the MD Anderson Symptom Inventory (MDASI-PeriOp-GYN) in patients who underwent open laparotomy.

Results: At discharge, patient-reported moderate to severe (≥4 on a 0-10 scale) abdominal bloating or abdominal cramping, combined with length of stay of ≥4 days, were found to be associated with a higher risk of 30-day post-operative grade II-IV complications by the Clavien-Dindo system (all p values < 0.01). Also, length of stay of ≥4 days and moderate to severe urinary urgency at discharge were found to be associated with the need for re-admission (all p values < 0.01).

Conclusion: This study defined the clinically meaningful symptoms that related to the risk of …

Loci On Chromosome 12q132 Encompassing Erbb3, Pa2g4 And Rab5b Are Associated With Polycystic Ovary Syndrome, R Alan Harris, Kellie J Archer, Mark O Goodarzi, Timothy P York, Jeffrey Rogers, Andrea Dunaif, Jan M Mcallister, Jerome F Strauss

Faculty, Staff and Students Publications

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenemia of ovarian theca cell origin. We report significant association of androgen production with 15 single nucleotide variants (SNVs) identified by exome sequencing of theca cells from women with PCOS and normal ovulatory women. Ten SNVs are located within a 150 kbp region on 12q13.2 which encompasses loci identified in PCOS genome-wide association studies (GWAS) and contains PCOS candidate genes ERBB3 and RAB5B. The region also contains PA2G4 which encodes a transcriptional corepressor of androgen receptor and androgen receptor-regulated genes. PA2G4 has not previously been recognized as related to PCOS in published …

An Integrative Approach For Exploring The Nature Of Fibroepithelial Neoplasms., Jihui Yun, Woohang Heo, Eun-Shin Lee, Deukchae Na, Wonyoung Kang, Jinjoo Kang, Jeesoo Chae, Dakyung Lee, Woochan Lee, Jinha Hwang, Tae-Kyung Yoo, Bok Sil Hong, Hye-Youn Son, Dong-Young Noh, Charles Lee, Hyeong-Gon Moon, Jong-Il Kim

Faculty Research 2023

BACKGROUND: Malignant phyllodes tumour (MPT) is a rare breast malignancy with epithelial and mesenchymal features. Currently, there are no appropriate research models or effective targeted therapeutic approaches for MPT.

METHODS: We collected fresh frozen tissues from nine patients with MPT and performed whole-exome and RNA sequencing. Additionally, we established patient-derived xenograft (PDX) models from patients with MPT and tested the efficacy of targeting dysregulated pathways in MPT using the PDX model from one MPT.

RESULTS: MPT has unique molecular characteristics when compared to breast cancers of epithelial origin and can be classified into two groups. The PDX model derived from …

Alphaviruses Detected In Mosquitoes In The North-Eastern Regions Of South Africa, 2014 To 2018, Milehna M Guarido, Isabel Fourie, Kgothatso Meno, Adriano Mendes, Megan A Riddin, Caitlin Macintyre, Sontaga Manyana, Todd Johnson, Maarten Schrama, Erin E Gorsich, Basil D Brooke, Antonio Paulo G Almeida, Marietjie Venter

Faculty, Staff and Student Publications

The prevalence and distribution of African alphaviruses such as chikungunya have increased in recent years. Therefore, a better understanding of the local distribution of alphaviruses in vectors across the African continent is important. Here, entomological surveillance was performed from 2014 to 2018 at selected sites in north-eastern parts of South Africa where alphaviruses have been identified during outbreaks in humans and animals in the past. Mosquitoes were collected using a net, CDC-light, and BG-traps. An alphavirus genus-specific nested RT-PCR was used for screening, and positive pools were confirmed by sequencing and phylogenetic analysis. We collected 64,603 mosquitoes from 11 genera, …

A Multicenter Study Of Clinical Impact Of Variant Of Uncertain Significance Reclassification In Breast, Ovarian And Colorectal Cancer Susceptibility Genes., Sukh Makhnoon, Brooke Levin, Megan Ensinger, Kristin Mattie, Robert J Volk, Zhongming Zhao, Tito Mendoza, Sanjay Shete, Laila Samiian, Generosa Grana, Andrew Grainger, Banu Arun, Brian H Shirts, Susan K Peterson

Oncology Articles

BACKGROUND: Clinical interpretation of genetic test results is complicated by variants of uncertain significance (VUS) that have an unknown impact on health but can be clarified through reclassification. There is little empirical evidence regarding VUS reclassification in oncology care settings, including the prevalence and outcomes of reclassification, and racial/ethnic differences.

METHODS: This was a retrospective analysis of persons with and without a personal history of cancer carrying VUS (with or without an accompanying pathogenic or likely pathogenic [P/LP] variant) in breast, ovarian, and colorectal cancer predisposition genes seen at four cancer care settings (in Texas, Florida, Ohio, and New Jersey) …

Sumoylation Regulates Functional Properties Of The Oocyte Transcription Factors Sohlh1 And Nobox, Bethany K Patton, Surabhi Madadi, Shawn M Briley, Avery A Ahmed, Stephanie A Pangas

Faculty, Staff and Students Publications

SOHLH1 and NOBOX are oocyte-expressed transcription factors with critical roles in ovary development and fertility. In mice, Sohlh1 and Nobox are essential for fertility through their regulation of the oocyte transcriptional network and cross-talk to somatic cells. Sumoylation is a posttranslational modification that regulates transcription factor function, and we previously showed that mouse oocytes deficient for sumoylation had an altered transcriptional landscape that included significant changes in NOBOX target genes. Here, we show that mouse SOHLH1 is modified by SUMO2/3 at lysine 345 and mutation of this residue alters SOHLH1 nuclear to cytoplasmic localization. In NOBOX, we identify a non-consensus …

Comparison Of Postoperative Outcomes Of Laparoscopic Vs Open Inguinal Hernia Repair, Jennie Meier, Audrey Stevens, Miles Berger, Konstantinos I Makris, Athanasios Bramos, Joan Reisch, C Munro Cullum, Simon C Lee, Celette Sugg Skinner, Herbert Zeh, Cynthia J Brown, Courtney J Balentine

Faculty, Staff and Students Publications

Importance: Advocates of laparoscopic surgery argue that all inguinal hernias, including initial and unilateral ones, should be repaired laparoscopically. Prior work suggests outcomes of open repair are improved by using local rather than general anesthesia, but no prior studies have compared laparoscopic surgery with open repair under local anesthesia.

Objective: To evaluate postoperative outcomes of open inguinal hernia repair under general or local anesthesia compared with laparoscopic repair.

Design, setting, and participants: This retrospective cohort study identified 107 073 patients in the Veterans Affairs Surgical Quality Improvement Program database who underwent unilateral initial inguinal hernia repair from 1998 to 2019. …