Medicine and Health Sciences Commons^™

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 …

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 …

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 …

Risk Factors For Hcc In Contemporary Cohorts Of Patients With Cirrhosis, Fasiha Kanwal, Saira Khaderi, Amit G Singal, Jorge A Marrero, Nicole Loo, Sumeet K Asrani, Christopher I Amos, Aaron P Thrift, Xiangjun Gu, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Etiological risk factors for cirrhosis have changed in the last decade. It remains unclear to what extent these trends in cirrhosis risk factors have changed HCC risk.

APPROACH AND RESULTS: We used data from two contemporary, prospective multiethnic cohorts of patients with cirrhosis: the Texas Hepatocellular Carcinoma Consortium Cohort and the Houston Veterans Administration Cirrhosis Surveillance Cohort. Patients with cirrhosis were enrolled from seven US centers and followed until HCC diagnosis, transplant, death, or June 30, 2021. We calculated the annual incidence rates for HCC and examined the effects of etiology, demographic, clinical, and lifestyle factors on …

Pediatric Consultation-Liaison Psychology: Insights And Lessons Learned During The Covid-19 Pandemic, Nicole M Schneider, Dara M Steinberg, Andrea M Garcia, Jessy Guler, Emily Mudd, A Monica Agoston, Katherine N Schwartzkopf, Kristin A Kullgren, Laura Judd-Glossy

Faculty, Staff and Students Publications

COVID-19 has presented a variety of challenges to the provision of psychology services. In the first month of the pandemic, pediatric consultation-liaison (CL) psychologists reported significant changes in methodology of service delivery (Steinberg et al. in Clin Pract Pediatr Psychol 9:1, 2020). To better understand how and if these changes persisted, as well as other emerging trends, a follow-up study examined changes and challenges six months into the pandemic. An anonymous questionnaire assessed topics related to pediatric CL psychology including practice changes, perception of changes, and institutional support. The questionnaire was sent to the APA Society of Pediatric Society's special …

Fetal Nephrology: A Quaternary Care Center Experience, Auda M Plaud Gonzalez, Catherine Joseph, Samantha R Stover, Ahmed Nassr, Chester J Koh, Joseph R Angelo, Michael C Braun

Faculty, Staff and Students Publications

Background: Congenital anomalies of the kidney and urinary tract (CAKUTs) represent 15%–20% of prenatally diagnosed abnormalities. Maternal characteristics, the frequency of various forms of kidney disease including CAKUT referred for prenatal nephrology consultation, and their perinatal outcomes are less well defined.

Methods: A retrospective chart review was performed of fetal CAKUT and other forms of kidney disease referred for prenatal nephrology consults at Texas Children's Hospital Fetal Center from January 1, 2012, to December 31, 2018.

Results: Two hundred seventeen prenatal nephrology consultations were performed during the study period, representing 4.7% of total Fetal Center referrals at a mean estimated …

Patterns Of Co-Occurring Birth Defects In Children With Anotia And Microtia, Jeremy M Schraw, Renata H Benjamin, Charles J Shumate, Mark A Canfield, Daryl A Scott, Scott D Mclean, Hope Northrup, Angela E Scheuerle, Christian P Schaaf, Joseph W Ray, Han Chen, A J Agopian, Philip J Lupo

Faculty, Staff and Student Publications

Many infants with anotia or microtia (A/M) have co-occurring birth defects, although few receive syndromic diagnoses in the perinatal period. Evaluation of co-occurring birth defects in children with A/M could identify patterns indicative of undiagnosed/unrecognized syndromes. We obtained information on co-occurring birth defects among infants with A/M for delivery years 1999-2014 from the Texas Birth Defects Registry. We calculated observed-to-expected ratios (OER) to identify birth defect combinations that occurred more often than expected by chance. We excluded children diagnosed with genetic or chromosomal syndromes from analyses. Birth defects and syndromes/associations diagnosed ≤1 year of age were considered. We identified 1310 …

Design Of Serena-6, A Phase Iii Switching Trial Of Camizestrant In Esr1-Mutant Breast Cancer During First-Line Treatment, Nicholas Turner, Cynthia Huang-Bartlett, Kevin Kalinsky, Massimo Cristofanilli, Giampaolo Bianchini, Stephen Chia, Hiroji Iwata, Wolfgang Janni, Cynthia X Ma, Erica L Mayer, Yeon Hee Park, Steven Fox, Xiaochun Liu, Sasha Mcclain, Francois-Clement Bidard

2020-Current year OA Pubs

No abstract provided.

Surgical Results Of The Lung Cancer Mutation Consortium 3 Trial: A Phase Ii Multicenter Single-Arm Study To Investigate The Efficacy And Safety Of Atezolizumab As Neoadjuvant Therapy In Patients With Stages Ib-Select Iiib Resectable Non-Small Cell Lung Cancer, Valerie W Rusch, G Alexander Patterson, Salama N Waqar, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Multimodality treatment for resectable non-small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non-small cell lung cancer and promising preoperatively in small clinical trials for resectable non-small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery.

METHODS: Patients with stage IB to select IIIB resectable non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was …

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

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 …

Prognostic Significance Of Acellular Mucin In Patients Undergoing Cytoreductive Surgery And Hyperthermic Intraperitoneal Chemotherapy (Crs/Hipec) For Appendiceal Neoplasms, Derek J Erstad, Kristen A Robinson, Karen Beaty, Safia Rafeeq, Yi-Ju Chiang, Kanwal Raghav, John P Shen, Michael J Overman, Wai Chin Foo, Melissa W Taggart, Paul F Mansfield, Richard E Royal, Keith F Fournier, Christopher P Scally

Faculty, Staff and Student Publications

Introduction: Appendiceal neoplasms have a propensity for peritoneal dissemination. The standard of care for select individuals is CRS/HIPEC. In the current 8th AJCC Staging system, a finding of only intraperitoneal acellular mucin (M1a) is classified as Stage IVa. There is concern that the current AJCC system may over-stage patients.

Methods: This was a single-institution retrospective review of 164 cases of mucinous appendiceal neoplasm. Patients undergoing CRS/HIPEC with M1a disease were compared to patients with peritoneal deposits containing tumor cells (well-differentiated adenocarcinoma; low-grade mucinous carcinoma peritonei-M1b,G1). Overall and recurrence-free survival were assessed.

Results: Median age was 51 years, 70% were female, …

The Presence Of A Single Nuchal Cord In The Third Trimester May Not Affect Tei Index In Lga Fetuses, Julia Murlewska, Przemysław Poszwa, Oskar Sylwestrzak, Maria Respondek-Liberska, Dennis Wood

Department of Obstetrics and Gynecology Faculty Papers

(1) Background: The aim of this study was to assess the RV (right ventricle) and LV (left ventricle) Tei index in large for gestational age (LGA) fetuses with a single 360-degree umbilical coil of the umbilical cord around the fetal neck identified by ultrasound in the third trimester of gestation. (2) Methods: The RV and LV Tei index for the cardiac function were measured in 297 singleton pregnancies, and we identified 25 LGA fetuses. There were 48% of LGA fetuses with a nuchal umbilical cord—LGA/NC—larger for gestational age fetuses with a nuchal cord. NC was detected with a color Doppler …

State Variation In Squamous Cell Carcinoma Of The Anus Incidence And Mortality, And Association With Hiv/Aids And Smoking In The United States, Haluk Damgacioglu, Yueh-Yun Lin, Ana Patricia Ortiz, Chi-Fang Wu, Zahed Shahmoradi, Shiang Shiuan Shyu, Ruosha Li, Alan G Nyitray, Keith Sigel, Gary M Clifford, Naomi Jay, Vivian Colon Lopez, Gregory M Barnell, Elizabeth Y Chiao, Elizabeth A Stier, Karen J Ortiz-Ortiz, Jeslie M Ramos-Cartagena, Kalyani Sonawane, Ashish A Deshmukh

Faculty, Staff and Student Publications

PURPOSE: Squamous cell carcinoma of the anus (SCCA) incidence and mortality rates are rising in the United States. Understanding state-level incidence and mortality patterns and associations with smoking and AIDS prevalence (key risk factors) could help unravel disparities and provide etiologic clues.

METHODS: Using the US Cancer Statistics and the National Center for Health Statistics data sets, we estimated state-level SCCA incidence and mortality rates. Rate ratios (RRs) were calculated to compare incidence and mortality in 2014-2018 versus 2001-2005. The correlations between SCCA incidence with current smoking (from the Behavioral Risk Factor Surveillance System) and AIDS (from the HIV Surveillance …

The Coronavirus Disease 2019 Pandemic Unmasked The Challenges Faced By Early-Stage Faculty In Infectious Diseases: A Call To Action, Erin M Scherer, Martin Backer, Karen Carvajal, Lara Danziger-Isakov, Sharon Frey, Leigh M Howard, Felicia Scaggs Huang, Angelica C Kottkamp, Tara Reid, Maria C Rodriguez-Barradas, Helen C Stankiewicz Karita, Zheyi Teoh, Anna Wald, Jennifer Whitaker, Zanthia Wiley, Igho Ofotokun, Kathryn M Edwards, Infectious Diseases Clinical Research Consortium (Idcrc) Mentorship Program Writing Group

Faculty, Staff and Students Publications

The coronavirus disease 2019 (COVID-19) pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for infectious diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, female faculty, underrepresented in medicine and science faculty and particularly ESF, experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and …

A Scoping Review Of Transgender Policies In The 15 Most Commonly Played Uk Professional Sports., Michael Mclarnon, Jane Thornton, Gail Knudson, Nigel Jones, Danny Glover, Andrew Murray, Michael Cummings, Neil Heron

Family Medicine Publications

INTRODUCTION: There has been much debate recently on the participation of transgender and gender-diverse (TGD) athletes in sport, particularly in relation to fairness, safety and inclusion. The 2021 IOC Framework on Fairness, Inclusion and Non-discrimination acknowledges the central role that eligibility criteria play in ensuring fairness, particularly in the female category, and states that athletes should not be excluded solely on the basis of their TGD identity.

AIMS: To identify policies that address TGD athlete participation in the 15 major United Kingdom (UK) sporting organisations and to summarise the evidence for each of these policies.

METHODS: A scoping review of …

Adjuvant Chemotherapy Versus Adjuvant Concurrent Chemoradiotherapy After Radical Surgery For Early-Stage Cervical Cancer: A Randomized, Non-Inferiority, Multicenter Trial, Danhui Weng, Huihua Xiong, Changkun Zhu, Xiaoyun Wan, Yaxia Chen, Xinyu Wang, Youzhong Zhang, Jie Jiang, Xi Zhang, Qinglei Gao, Gang Chen, Hui Xing, Changyu Wang, Kezhen Li, Yaheng Chen, Yuyan Mao, Dongxiao Hu, Zimin Pan, Qingqin Chen, Baoxia Cui, Kun Song, Cunjian Yi, Guangcai Peng, Xiaobing Han, Ruifang An, Liangsheng Fan, Wei Wang, Tingchuan Xiong, Yile Chen, Zhenzi Tang, Lin Li, Xingsheng Yang, Xiaodong Cheng, Weiguo Lu, Hui Wang, Beihua Kong, Xing Xie, Ding Ma

Faculty, Staff and Student Publications

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant …

A Close-Up Examination Of Racial Disparities In Infant And Maternal Outcomes In Montgomery County, Ohio, Kelsey M. Harman, Keith M. Reisinger-Kindle, Rose Maxwell

Obstetrics and Gynecology Faculty Publications

Background: Infant and maternal outcomes in Montgomery County, Ohio, are among the worst in the state and rival that of many low-income nations. This study compares maternal and infant outcomes across 3 zip codes in Montgomery County to discern factors that are influencing health outcomes for their residents. The zip codes represent 3 distinct communities with unique racial and socioeconomic makeups.  Methods: A cohort of maternal-infant dyads (n=5098) who delivered at Miami Valley Hospital and Good Samaritan Hospital from January 1, 2009, to January 1, 2019, were analyzed via retrospective chart review. Maternal (MCS) and infant (ICS) outcome composite scores …

Developmental Programming: Adverse Sexually Dimorphic Transcriptional Programming Of Gestational Testosterone Excess In Cardiac Left Ventricle Of Fetal Sheep, Venkateswaran Ramamoorthi Elangovan, Nadia Saadat, Adel Ghnenis, Vasantha Padmanabhan, Arpita K Vyas

2020-Current year OA Pubs

Adverse in-utero insults during fetal life alters offspring's developmental trajectory, including that of the cardiovascular system. Gestational hyperandrogenism is once such adverse in-utero insult. Gestational testosterone (T)-treatment, an environment of gestational hyperandrogenism, manifests as hypertension and pathological left ventricular (LV) remodeling in adult ovine offspring. Furthermore, sexual dimorphism is noted in cardiomyocyte number and morphology in fetal life and at birth. This study investigated transcriptional changes and potential biomarkers of prenatal T excess-induced adverse cardiac programming. Genome-wide coding and non-coding (nc) RNA expression were compared between prenatal T-treated (T propionate 100 mg intramuscular twice weekly from days 30 to 90 …

Combination Of Epha2- And Wee1-Targeted Therapies In Endometrial Cancer, Santosh K Dasari, Robiya Joseph, Sujanitha Umamaheswaran, Lingegowda S Mangala, Emine Bayraktar, Cristian Rodriguez-Aguayo, Yutuan Wu, Nghi Nguyen, Reid T Powell, Mary Sobieski, Yuan Liu, Mamur A Chowdhury, Paola Amero, Clifford Stephan, Gabriel Lopez-Berestein, Shannon N Westin, Anil K Sood

Faculty, Staff and Student Publications

EphA2 tyrosine kinase is upregulated in many cancers and correlated with poor survival of patients, including those with endometrial cancer. EphA2-targeted drugs have shown modest clinical benefit. To improve the therapeutic response to such drugs, we performed a high-throughput chemical screen to discover novel synergistic partners for EphA2-targeted therapeutics. Our screen identified the Wee1 kinase inhibitor, MK1775, as a synergistic partner to EphA2, and this finding was confirmed using both in vitro and in vivo experiments. We hypothesized that Wee1 inhibition would sensitize cells to EphA2-targeted therapy. Combination treatment decreased cell viability, induced apoptosis, and reduced clonogenic potential in endometrial …

Depatuxizumab Mafodotin In Egfr-Amplified Newly Diagnosed Glioblastoma: A Phase Iii Randomized Clinical Trial, Andrew B Lassman, Stephanie L Pugh, Tony J C Wang, Kenneth Aldape, Hui K Gan, Matthias Preusser, Michael A Vogelbaum, Erik P Sulman, Minhee Won, Peixin Zhang, Golnaz Moazami, Marian S Macsai, Mark R Gilbert, Earle E Bain, Vincent Blot, Peter J Ansell, Suvajit Samanta, Madan G Kundu, Terri S Armstrong, Jeffrey S Wefel, Clemens Seidel, Filip Y De Vos, Sigmund Hsu, Andrés F Cardona, Giuseppe Lombardi, Dmitry Bentsion, Richard A Peterson, Craig Gedye, Véronique Bourg, Antje Wick, Walter J Curran, Minesh P Mehta

Faculty, Staff and Student Publications

BACKGROUND: Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor epidermal growth factor receptor gene amplification (EGFR-amp). Preclinical and early-phase clinical data suggested efficacy of depatuxizumab mafodotin (depatux-m), an antibody-drug conjugate comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs.

METHODS: In this phase III trial, adults with centrally confirmed, EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo. Corneal epitheliopathy was treated with a combination of protocol-specified prophylactic and supportive measures. There was 85% power to detect a hazard ratio (HR) ≤0.75 for overall survival …

Rna Profiling Of Human Dorsal Root Ganglia Reveals Sex Differences In Mechanisms Promoting Neuropathic Pain, Pradipta R Ray, Stephanie Shiers, James P Caruso, Diana Tavares-Ferreira, Ishwarya Sankaranarayanan, Megan L Uhelski, Yan Li, Robert Y North, Claudio Tatsui, Gregory Dussor, Michael D Burton, Patrick M Dougherty, Theodore J Price

Faculty, Staff and Student Publications

Neuropathic pain is a leading cause of high-impact pain, is often disabling and is poorly managed by current therapeutics. Here we focused on a unique group of neuropathic pain patients undergoing thoracic vertebrectomy where the dorsal root ganglia is removed as part of the surgery allowing for molecular characterization and identification of mechanistic drivers of neuropathic pain independently of preclinical models. Our goal was to quantify whole transcriptome RNA abundances using RNA-seq in pain-associated human dorsal root ganglia from these patients, allowing comprehensive identification of molecular changes in these samples by contrasting them with non-pain-associated dorsal root ganglia. We sequenced …

Visualization Of Preimplantation Uterine Fluid Absorption In Mice Using Alexa Fluor™ 488 Hydrazide†, Yuehuan Li, Taylor Elijah Martin, Jonathan Matthew Hancock, Rong Li, Suvitha Viswanathan, John P Lydon, Yi Zheng, Xiaoqin Ye

Faculty, Staff and Students Publications

Uterine fluid plays important roles in supporting early pregnancy events and its timely absorption is critical for embryo implantation. In mice, its volume is maximum on day 0.5 post-coitum (D0.5) and approaches minimum upon embryo attachment ~D4.0. Its secretion and absorption in ovariectomized rodents were shown to be promoted by estrogen and progesterone (P4), respectively. The temporal mechanisms in preimplantation uterine fluid absorption remain to be elucidated. We have established an approach using intraluminally injected Alexa Fluor™ 488 Hydrazide (AH) in preimplantation control (RhoAf/f) and P4-deficient RhoAf/fPgrCre/+ mice. In control mice, bulk entry (seen as smeared cellular staining) via uterine …

A Phase Ib/Ii Study Of Lenvatinib And Pembrolizumab In Advanced Endometrial Carcinoma (Study 111/Keynote-146): Long-Term Efficacy And Safety Update, Vicky Makker, Carol Aghajanian, Allen L Cohn, Margarita Romeo, Raquel Bratos, Marcia S Brose, Mark Messing, Lea Dutta, Corina E Dutcus, Jie Huang, Emmett V Schmidt, Robert Orlowski, Matthew H Taylor

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The open-label phase Ib/II Study 111/KEYNOTE-146 of daily lenvatinib 20 mg plus pembrolizumab 200 mg once every 3 weeks showed promising efficacy and tolerable safety in patients with previously treated advanced endometrial carcinoma (EC; primary data cutoff …

Health Benefits And Cost-Effectiveness Of Children's Oncology Group Breast Cancer Screening Guidelines For Chest-Irradiated Hodgkin Lymphoma Survivors, F Lennie Wong, Janie M Lee, Wendy M Leisenring, Joseph P Neglia, Rebecca M Howell, Susan A Smith, Kevin C Oeffinger, Chaya S Moskowitz, Tara O Henderson, Ann Mertens, Paul C Nathan, Yutaka Yasui, Wendy Landier, Gregory T Armstrong, Leslie L Robison, Smita Bhatia

Faculty, Staff and Student Publications

Purpose: To evaluate the outcomes and cost-effectiveness of the Children's Oncology Group Guideline recommendation for breast cancer (BC) screening using mammography (MAM) and breast magnetic resonance imaging (MRI) in female chest-irradiated childhood Hodgkin lymphoma (HL) survivors. Digital breast tomosynthesis (DBT), increasingly replacing MAM in practice, was also examined.

Methods: Life years (LYs), quality-adjusted LYs (QALYs), BC mortality, health care costs, and false-positive screen frequencies of undergoing annual MAM, DBT, MRI, MAM + MRI, and DBT + MRI from age 25 to 74 years were estimated by microsimulation. BC risks and non-BC mortality were estimated from female 5-year survivors of …

A Phase Ib/Ii Study Of Lenvatinib And Pembrolizumab In Advanced Endometrial Carcinoma (Study 111/Keynote-146): Long-Term Efficacy And Safety Update., Vicky Makker, Carol Aghajanian, Allen L Cohn, Margarita Romeo, Raquel Bratos, Marcia S Brose, Mark Messing, Lea Dutta, Corina E Dutcus, Jie Huang, Emmett V Schmidt, Robert Orlowski, Matthew H Taylor

Department of Medicine Faculty Papers

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The open-label phase Ib/II Study 111/KEYNOTE-146 of daily lenvatinib 20 mg plus pembrolizumab 200 mg once every 3 weeks showed promising efficacy and tolerable safety in patients with previously treated advanced endometrial carcinoma (EC; primary data cutoff …

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 = …

Incidence And Clearance Of Anal Human Papillomavirus Infection In 16 164 Individuals, According To Human Immunodeficiency Virus Status, Sex, And Male Sexuality: An International Pooled Analysis Of 34 Longitudinal Studies, Feixue Wei, Marc T Goodman, Ningshao Xia, Jun Zhang, Anna R Giuliano, Gypsyamber D'Souza, Nancy A Hessol, Maarten F Schim Van Der Loeff, Jianghong Dai, Karin Neukam, Alexandra De Pokomandy, I Mary Poynten, Ronald B Geskus, Joaquin Burgos, Isabelle Etienney, Anna-Barbara Moscicki, Maria Gabriella Donà, Maura L Gillison, Alan G Nyitray, Rebecca G Nowak, Evy Yunihastuti, Huachun Zou, Carmen Hidalgo-Tenorio, Nittaya Phanuphak, Jean-Michel Molina, Alice M Schofield, Stephen Kerr, Song Fan, Yong Lu, Jason J Ong, Admire T Chikandiwa, Sirinya Teeraananchai, Nicola Squillace, Dorothy J Wiley, Joel M Palefsky, Damien Georges, Catharina J Alberts, Gary M Clifford

Faculty, Staff and Student Publications

Background: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized.

Methods: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their …

Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Testing And Detection During Peripartum Hospitalizations Among A Multicenter Cohort Of Pregnant Persons: March 2020-February 2021, Miranda J Delahoy, Flor Munoz, De-Kun Li, Carmen Sofia Arriola, Nanette Lee Bond, Michael Daugherty, Jeannette Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Stephanie A Irving, Mary Juergens, Venkatesh Kancharla, Mara Greenberg, Roxana Odouli, Gabriella Newes-Adeyi, Erin G Nicholson, Lawrence Reichle, Momodou Sanyang, Margaret Snead, Fatimah S Dawood, Allison L Naleway

Faculty, Staff and Students Publications

BACKGROUND: Identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden.

METHODS: This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 US integrated healthcare networks (sites 1-3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020-February 2021 and ≥1 antenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing …

Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Testing And Detection During Peripartum Hospitalizations Among A Multicenter Cohort Of Pregnant Persons: March 2020-February 2021, Miranda J Delahoy, Flor Munoz, De-Kun Li, Carmen Sofia Arriola, Nanette Lee Bond, Michael Daugherty, Jeannette Ferber, Nickolas Ferguson, Louise Hadden, Jillian T Henderson, Stephanie A Irving, Mary Juergens, Venkatesh Kancharla, Mara Greenberg, Roxana Odouli, Gabriella Newes-Adeyi, Erin G Nicholson, Lawrence Reichle, Momodou Sanyang, Margaret Snead, Fatimah S Dawood, Allison L Naleway

Faculty, Staff and Students Publications

BACKGROUND: Identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden.

METHODS: This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 US integrated healthcare networks (sites 1-3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020-February 2021 and ≥1 antenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing …