Medical Specialties Commons^™

Dll3 As An Emerging Target For The Treatment Of Neuroendocrine Neoplasms, James Yao, Emily Bergsland, Rahul Aggarwal, Ana Aparicio, Himisha Beltran, Judy S. Crabtree, Christine L. Hann, Toni Ibrahim, Lauren A. Byers, Hironobu Sasano, John Umejiego, Marianne Pavel

School of Medicine Faculty Publications

Introduction: Neuroendocrine neoplasms (NEN) are heterogeneous malignancies that can arise at almost any anatomical site and are classified as biologically distinct well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC). Current systemic therapies for advanced disease, including targeted therapies, chemotherapy, and immunotherapy, are associated with limited duration of response. New therapeutic targets are needed. One promising target is delta-like ligand 3 (DLL3), an inhibitory ligand of the Notch receptor whose overexpression on the surface of NEN is associated with tumorigenesis. Methods: This article is a narrative review that highlights the role of DLL3 in NEN progression and prognosis, the …

Daratumumab Plus Lenalidomide, Bortezomib And Dexamethasone In Newly Diagnosed Multiple Myeloma: Analysis Of Vascular Thrombotic Events In The Griffin Study., Douglas W Sborov, Muhamed Baljevic, Brandi Reeves, Jacob Laubach, Yvonne A Efebera, Cesar Rodriguez, Luciano J Costa, Ajai Chari, Rebecca Silbermann, Sarah A Holstein, Larry D Anderson, Jonathan L Kaufman, Nina Shah, Huiling Pei, Sharmila Patel, Annelore Cortoos, J Blake Bartlett, Jessica Vermeulen, Thomas S Lin, Peter M Voorhees, Paul G Richardson

Oncology Articles

Patients with multiple myeloma are at increased risk of vascular thromboembolic events (VTEs). This post hoc analysis evaluated VTEs in the randomised phase 2 GRIFFIN study (ClinicalTrials.gov Identifier: NCT02874742) that investigated lenalidomide/bortezomib/dexamethasone (RVd) ± daratumumab (D). Patients with newly diagnosed multiple myeloma who were eligible for autologous stem cell transplantation (ASCT) received D-RVd/RVd induction, high-dose therapy and ASCT, D-RVd/RVd consolidation and up to 2 years of lenalidomide maintenance therapy ± D. VTE prophylaxis was recommended (at least aspirin, ≥162 mg daily) in accordance with International Myeloma Working Group guidelines. In the safety population (D-RVd, n = 99; RVd, n = …

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …

An Evaluation Of Peer-Rated Surgical Skill And Its Relationship With Detrusor Muscle Sampling In Transurethral Resection Of Bladder Tumor, Minh N Pham, Oliver S Ko, Reiping Huang, Amanda X Vo, Kyle P Tsai, Jeremy D Lai, Matthew T Hudnall, Joshua A Halpern, Joshua J Meeks, Jonas Benson, Ricardo Soares, Ronald Kim, Karl Y Bilimoria, Jonah J Stulberg, Gregory B Auffenberg

Faculty, Staff and Student Publications

OBJECTIVE: To assess the reliability of peer-review of TURBT videos as a means to evaluate surgeon skill and its relationship to detrusor sampling.

METHODS: Urologists from an academic health system submitted TURBT videos in 2019. Ten blinded peers evaluated each surgeon's performance using a 10-item scoring instrument to quantify surgeon skill. Normalized composite skill scores for each surgeon were calculated using peer ratings. For surgeons submitting videos, we retrospectively reviewed all TURBT pathology results (2018-2019) to assess surgeon-specific detrusor sampling. A hierarchical logistic regression model was fit to evaluate the association between skill and detrusor sampling, adjusting for patient and …

Nocturnal Dipping And Kidney Function Decline: Findings From The Ckd In Children Study, Christine Y Bakhoum, Manali Phadke, Yanhong Deng, Joshua A Samuels, Pranav S Garimella, Susan L Furth, F Perry Wilson, Joachim H Ix

Faculty, Staff and Student Publications

INTRODUCTION: Normally, blood pressure (BP) declines by at least 10% from daytime to nighttime. In adults, blunted nocturnal dipping has been associated with more rapid decline in kidney function. Nondipping is prevalent in children with chronic kidney disease (CKD). We sought to determine whether nondipping is associated with proteinuria and progression to kidney failure in children with CKD.

METHODS: In the prospective CKD in children (CKiD) cohort, Cox proportional hazards models were used to evaluate the relationship between baseline nondipping and progression to kidney failure. Linear mixed effects models were used to evaluate the relationship between nondipping and changes in …

Examining The Effects Of Formal Education Level On The Montreal Cognitive Assessment, Renee S. White, Justin M. Barber, Jordan P. Harp, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Background: Brief, global assessments such as the Montreal Cognitive Assessment (MoCA) are widely used in primary care for assessing cognition in older adults. Like other neuropsychological instruments, lower formal education can influence MoCA interpretation.

Methods: Data from 2 large studies of cognitive aging were used—Alzheimer’s Disease Neuroimaging Initiative (ADNI) and National Alzheimer’s Coordinating Center (NACC). Both use comprehensive examinations to determine cognitive status and have brain amyloid status for many participants. Mixed models were used to account for random variation due to data source.

Results: Cognitively intact participants with lower education (≤12 years) were more likely than …

Multiple Gene Variants Linked To Alzheimer's-Type Clinical Dementia Via Gwas Are Also Associated With Non-Alzheimer's Neuropathologic Entities, Yuriko Katsumata, Lincoln M. P. Shade, Timothy J. Hohman, Julie A. Schneider, David A. Bennett, Jose M. Farfel, Walter A. Kukull, David W. Fardo, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

The classic pathologic hallmarks of Alzheimer’s disease (AD) are amyloid plaques and neurofibrillary tangles (AD neuropathologic changes, or ADNC). However, brains from individuals clinically diagnosed with “AD-type” (amnestic) dementia usually harbor heterogeneous neuropathologies in addition to, or other than, ADNC. We hypothesized that some AD-type dementia associated genetic single nucleotide variants (SNVs) identified from large genomewide association studies (GWAS) were associated with non-ADNC neuropathologies. To test this hypothesis, we analyzed data from multiple studies with available genotype and neuropathologic phenotype information. Clinical AD/dementia risk alleles of interest were derived from the very large GWAS by Bellenguez et al. (2022) who …

Outpatient Surgery For Rib Fracture Fixation: A Report Of Three Cases., Daniel T Degenova, Nolan P Schmitz, Jia Bao Lin, Travis J Jones, Benjamin C Taylor

Surgery Articles

Rib fractures are common injuries observed in trauma patients that will often heal without operative intervention. However, patients can infrequently have continued pain. Operative fixation of these symptomatic rib fractures has traditionally led to the patient requiring hospital admission for observation and pain control. The purpose of this study was to review three cases of outpatient rib fracture, open reduction and internal fixation (ORIF) surgery. Three patients with symptomatic rib fractures treated with ORIF at a single urban level one trauma center underwent outpatient same-day surgery. Pertinent demographic, clinical, radiographic, and surgical data were collected. All patients had decreased preoperative …

A Rare Cause Of Urticaria In An Nsaid Tolerant Patient, Thao Le, Mary K. Mcleod, Laurianne Wild

Posters

Introduction: Acetaminophen is one of the most used anti-pyretics to mitigate fever. Few cases have been reported of hypersensitivity reactions to acetaminophen without non-steroidal anti-inflammatory drug (NSAID) intolerance. It is recommended that if there is suspected drug hypersensitivity then the patient should undergo an oral drug challenge. Case Description: A 49-year-old male presented for evaluation of urticaria that occurred with acetaminophen ingestion. He reported several episodes where he developed diffuse urticaria within 15 minutes of ingestion, but no other symptoms concerning for anaphylaxis. He was unsure of the dose. He also noted urticaria with Excedrin migraine, which contains acetaminophen, aspirin, …

Improving Fluid Management Of Extreme Premature Infants By Providing A Restrictive Fluid Management Algorithm In The Icn, Jacob S. Ward, Dena Hubbard, Nicholas Clark

Posters

Intro: Excessive fluid intake in extremely premature infants during the first week of life is known to increase risk of adverse events such as necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), and overall mortality. There also is some correlation with the need for mechanical ventilation and development bronchopulmonary dysplasia (BPD). While fluid restriction is recommended to decrease the likelihood of adverse outcomes, at our institution we found there was a wide variability in and lack of evidence-based standards on fluid management in this vulnerable population. We aimed to improve the fluid management of the extremely premature infants by standardizing a …

Membership And Feedback On The American Academy Of Orthopaedic Surgeons And Other Subspecialty Societies: A Survey Study Of Orthopaedic Surgeons., Arjun Saxena, Gregory R Toci, Parker L Brush, Alexis Reinhardt, Pedro K Beredjiklian, Alan S. Hilibrand, Alex R. Vaccaro, Daniel Fletcher

Rothman Institute Papers

Introduction: Orthopaedic surgeons face decreased reimbursement, lower income, and increased rates of burnout. As subspecializing through fellowship training in orthopaedics becomes more and more prevalent, the value of membership to a general orthopaedic society (American Academy of Orthopaedic Surgeons [AAOS]) warrants investigation.

Methods: One hundred thirty orthopaedic surgeons were surveyed by e-mail through a 14-item anonymous survey administered through SurveyMonkey. The survey inquired about surgeon experience, practice type, fellowship training, and details regarding AAOS and subspecialty society membership.

Results: The response rate was 67%, with 94% of respondents indicating that they were members of AAOS and a subspecialty society. The …

Safety Of Simultaneous Bilateral Intravitreal Versus Unilateral Anti-Vasculo-Endothelial Growth Factors Injection In An Operating Room Setting, Irfan Kabiruddin Jeeva, Sidra Masud, Rehman Siddiqui, Hadees Murad Fahad

Department of Ophthalmology & Visual Sciences

Objectives: Chorioretinal diseases requiring the use of anti-vascular endothelial growth (anti-VEGF) injections often occur in both eyes simultaneously. This can necessitate injecting both eyes together rather than one eye at a time. The purpose of the study was to determine whether simultaneous bilateral intravitreal injections of anti-VEGF agents are safe when administered in an operation theatre setting.
Methods: Retrospective review of data was conducted. Single center study conducted in a tertiary care hospital in Karachi Pakistan. Approximately 30,000 eyes that received anti-VEGF injection during a 10-year study period were included (March 2008-February 2018). Patients who were lost to follow up …

Use Of A Microsimulation Method For Assessing Dynamics Of Smoking Status And Gains In Life Expectancy After Quitting In A Longitudinal Cohort Of Us Older Adults, Haomiao Jia, Erica I. Lubetkin

Publications and Research

Objectives: Previous studies were unable to estimate the dynamics of smoking status in the US elderly general population, and no study has assessed the benefit of quitting in terms of resultant gains in life expectancy. We proposed a novel method to estimate the per cent of quitting in remaining lifetime, successful quitting and relapse, as well as life expectancy by participants' baseline smoking status.

Design: Longitudinal cohort.

Setting: US community-dwelling population.

Participants: Respondents from the Medicare Health Outcome Survey Cohort 15 (baseline 2012, follow-up 2014). We included respondents who were aged ≥65 years and alive at the baseline and participated …

Stroke Genetics Informs Drug Discovery And Risk Prediction Across Ancestries, Aniket Mishra, Rainer Malik, Tsuyoshi Hachiya, Tuuli Jürgenson, Shinichi Namba, Daniel C Posner, Frederick K Kamanu, Masaru Koido, Quentin Le Grand, Mingyang Shi, Yunye He, Marios K Georgakis, Ilana Caro, Kristi Krebs, Yi-Ching Liaw, Felix C Vaura, Kuang Lin, Bendik Slagsvold Winsvold, Vinodh Srinivasasainagendra, Livia Parodi, Hee-Joon Bae, Ganesh Chauhan, Michael R Chong, Liisa Tomppo, Rufus Akinyemi, Gennady V Roshchupkin, Naomi Habib, Yon Ho Jee, Jesper Qvist Thomassen, Vida Abedi, Jara Cárcel-Márquez, Marianne Nygaard, Hampton L Leonard, Chaojie Yang, Ekaterina Yonova-Doing, Maria J Knol, Adam J Lewis, Renae L Judy, Tetsuro Ago, Philippe Amouyel, Nicole D Armstrong, Mark K Bakker, Traci M Bartz, David A Bennett, Joshua C Bis, Constance Bordes, Sigrid Børte, Anael Cain, Paul M Ridker, Kelly Cho, Zhengming Chen, Carlos Cruchaga, John W Cole, Phil L De Jager, Rafael De Cid, Matthias Endres, Leslie E Ferreira, Mirjam I Geerlings, Natalie C Gasca, Vilmundur Gudnason, Jun Hata, Jing He, Alicia K Heath, Yuk-Lam Ho, Aki S Havulinna, Jemma C Hopewell, Hyacinth I Hyacinth, Michael Inouye, Mina A Jacob, Christina E Jeon, Christina Jern, Masahiro Kamouchi, Keith L Keene, Takanari Kitazono, Steven J Kittner, Takahiro Konuma, Amit Kumar, Paul Lacaze, Lenore J Launer, Keon-Joo Lee, Kaido Lepik, Jiang Li, Liming Li, Ani Manichaikul, Hugh S Markus, Nicholas A Marston, Thomas Meitinger, Braxton D Mitchell, Felipe A Montellano, Takayuki Morisaki, Thomas H Mosley, Mike A Nalls, Børge G Nordestgaard, Martin J O'Donnell, Yukinori Okada, N Charlotte Onland-Moret, Bruce Ovbiagele, Annette Peters, Bruce M Psaty, Stephen S Rich, Jonathan Rosand, Marc S Sabatine, Ralph L Sacco, Danish Saleheen, Else Charlotte Sandset, Veikko Salomaa, Muralidharan Sargurupremraj, Makoto Sasaki, Claudia L Satizabal, Carsten O Schmidt, Atsushi Shimizu, Nicholas L Smith, Kelly L Sloane, Yoichi Sutoh, Yan V Sun, Kozo Tanno, Steffen Tiedt, Turgut Tatlisumak, Nuria P Torres-Aguila, Hemant K Tiwari, David-Alexandre Trégouët, Stella Trompet, Anil Man Tuladhar, Anne Tybjærg-Hansen, Marion Van Vugt, Riina Vibo, Shefali S Verma, Kerri L Wiggins, Patrik Wennberg, Daniel Woo, Peter W F Wilson, Huichun Xu, Qiong Yang, Kyungheon Yoon, Compass Consortium, Invent Consortium, Dutch Parelsnoer Initiative (Psi) Cerebrovascular Disease Study Group, Estonian Biobank, Precise4q Consortium, Finngen Consortium, Ninds Stroke Genetics Network (Sign), Megastroke Consortium, Siren Consortium, China Kadoorie Biobank Collaborative Group, Va Million Veteran Program, International Stroke Genetics Consortium (Isgc), Biobank Japan, Charge Consortium, Gigastroke Consortium, Iona Y Millwood, Christian Gieger, Toshiharu Ninomiya, Hans J Grabe, J Wouter Jukema, Ina L Rissanen, Daniel Strbian, Young Jin Kim, Pei-Hsin Chen, Ernst Mayerhofer, Joanna M M Howson, Marguerite R Irvin, Hieab Adams, Sylvia Wassertheil-Smoller, Kaare Christensen, Mohammad A Ikram, Tatjana Rundek, Bradford B Worrall, G Mark Lathrop, Moeen Riaz, Eleanor M Simonsick, Janika Kõrv, Paulo H C França, Ramin Zand, Kameshwar Prasad, Ruth Frikke-Schmidt, Frank-Erik De Leeuw, Thomas Liman, Karl Georg Haeusler, Ynte M Ruigrok, Peter Ulrich Heuschmann, W T Longstreth, Keum Ji Jung, Lisa Bastarache, Guillaume Paré, Scott M Damrauer, Daniel I Chasman, Jerome I Rotter, Christopher D Anderson, John-Anker Zwart, Teemu J Niiranen, Myriam Fornage, Yung-Po Liaw, Sudha Seshadri, Israel Fernández-Cadenas, Robin G Walters, Christian T Ruff, Mayowa O Owolabi, Jennifer E Huffman, Lili Milani, Yoichiro Kamatani, Martin Dichgans, Stephanie Debette

Faculty, Staff and Student Publications

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary …

Lessons From The Failure To Complete A Trial Of Denosumab In Women With A Pathogenic Brca1/2 Variant Scheduling Risk-Reducing Salpingo-Oophorectomy, Meghna S Trivedi, Nadir Arber, Eitan Friedman, Judy E Garber, Kevin Holcomb, Neil S Horowitz, Jason D Wright, J Jack Lee, Lana A Vornik, Saba Abutaseh, Tawana Castile, Edward R Sauter, Eileen Dimond, Brandy M Heckman-Stoddard, Margaret House, Goli Samimi, Powel H Brown, Katherine D Crew

Faculty, Staff and Student Publications

Female carriers of pathogenic/likely pathogenic (P/LP) BRCA1/2 variants are at increased risk of developing breast and ovarian cancer. Currently, the only effective strategy for ovarian cancer risk reduction is risk-reducing bilateral salpingo-oophorectomy (RR-BSO), which carries adverse effects related to early menopause. There is ongoing investigation of inhibition of the RANK ligand (RANKL) with denosumab as a means of chemoprevention for breast cancer in carriers of BRCA1 P/LP variants. Through the NCI Division of Cancer Prevention (DCP) Early Phase Clinical Trials Prevention Consortia, a presurgical pilot study of denosumab was developed in premenopausal carriers of P/LP BRCA1/2 variants scheduled for RR-BSO …

Estimation Of Tumor Cell Total Mrna Expression In 15 Cancer Types Predicts Disease Progression, Shaolong Cao, Jennifer R Wang, Shuangxi Ji, Peng Yang, Yaoyi Dai, Shuai Guo, Matthew D Montierth, John Paul Shen, Xiao Zhao, Jingxiao Chen, Jaewon James Lee, Paola A Guerrero, Nicholas Spetsieris, Nikolai Engedal, Sinja Taavitsainen, Kaixian Yu, Julie Livingstone, Vinayak Bhandari, Shawna M Hubert, Najat C Daw, P Andrew Futreal, Eleni Efstathiou, Bora Lim, Andrea Viale, Jianjun Zhang, Matti Nykter, Bogdan A Czerniak, Powel H Brown, Charles Swanton, Pavlos Msaouel, Anirban Maitra, Scott Kopetz, Peter Campbell, Terence P Speed, Paul C Boutros, Hongtu Zhu, Alfonso Urbanucci, Jonas Demeulemeester, Peter Van Loo, Wenyi Wang

Faculty, Staff and Student Publications

Single-cell RNA sequencing studies have suggested that total mRNA content correlates with tumor phenotypes. Technical and analytical challenges, however, have so far impeded at-scale pan-cancer examination of total mRNA content. Here we present a method to quantify tumor-specific total mRNA expression (TmS) from bulk sequencing data, taking into account tumor transcript proportion, purity and ploidy, which are estimated through transcriptomic/genomic deconvolution. We estimate and validate TmS in 6,590 patient tumors across 15 cancer types, identifying significant inter-tumor variability. Across cancers, high TmS is associated with increased risk of disease progression and death. TmS is influenced by cancer-specific patterns of gene …

Ovarian Steroid Cell Tumors, Not Otherwise Specified: Analysis Of Nine Cases With A Literature Review, Mengyan Lin, Kechun Bao, Lingjia Lu, Shuhang Xu, Yun Liang, Xiaodong Cheng, Fenfen Wang

Faculty, Staff and Student Publications

BACKGROUND: Ovarian steroid cell tumors (SCTs), not otherwise specified (NOS), are rare, with few large studies. The purpose of this study was to analyze the clinical features, prognosis, and treatment choices for these patients of different age groups.

METHODS: This was a retrospective study. We identified nine cases of ovarian steroid cell tumor, not otherwise specified, confirmed by post-operative histopathological examination, and analyzed clinical features, surgical procedures, and follow up outcomes. We also reviewed cases reports of ovarian steroid cell tumors, not otherwise specified.

RESULTS: A total of nine cases were included. The age range was 9-68 years (mean, 41.89 …

Risks Of Depression And Suicide After Diagnosis With Heart Failure: A National Cohort Study, Casey Crump, Jan Sundquist, Kenneth S Kendler, Weiva Sieh, Alexis C Edwards, Kristina Sundquist

Faculty, Staff and Student Publications

BACKGROUND: Heart failure (HF) has been associated with psychosocial distress, but other long-term mental health sequelae are unclear.

OBJECTIVES: In this study, the authors sought to determine risks of major depression and suicide, susceptible time periods, and sex-specific differences after HF diagnosis in a large population-based cohort.

METHODS: A national cohort study was conducted of all 154,572 persons diagnosed with HF at ages 18-75 years during 2002-2017 in Sweden and 1,545,720 age- and sex-matched population-based control subjects who were followed up for major depression and suicide ascertained from nationwide inpatient, outpatient, and death records through 2018. Poisson regression was used …

Image Analysis Reveals Differences In Tumor Multinucleations In Black And White Patients With Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma, Can F Koyuncu, Reetoja Nag, Cheng Lu, Germán Corredor, Vidya S Viswanathan, Vlad C Sandulache, Pingfu Fu, Kailin Yang, Quintin Pan, Zelin Zhang, Jun Xu, Deborah J Chute, Wade L Thorstad, Farhoud Faraji, Justin A Bishop, Mitra Mehrad, Patricia D Castro, Andrew G Sikora, Lester D R Thompson, Rebecca D Chernock, Krystle A Lang Kuhs, Jay K Wasman, Jingqin R Luo, David J Adelstein, Shlomo A Koyfman, James S Lewis, Anant Madabhushi

Faculty, Staff and Student Publications

BACKGROUND: Understanding biological differences between different racial groups of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) patients, who have differences in terms of incidence, survival, and tumor morphology, can facilitate accurate prognostic biomarkers, which can help develop personalized treatment strategies.

METHODS: This study evaluated whether there were morphologic differences between HPV-associated tumors from Black and White patients in terms of multinucleation index (MuNI), an image analysis-derived metric that measures density of multinucleated tumor cells within epithelial regions on hematoxylin-eosin images and previously has been prognostic in HPV-associated OPSCC patients. In this study, the authors specifically evaluated whether the same …

Structural Brain Alterations Associated With Suicidal Thoughts And Behaviors In Young People: Results From 21 International Studies From The Enigma Suicidal Thoughts And Behaviours Consortium, Laura S Van Velzen, Maria R Dauvermann, Lejla Colic, Luca M Villa, Hannah S Savage, Yara J Toenders, Alyssa H Zhu, Joanna K Bright, Adrián I Campos, Lauren E Salminen, Sonia Ambrogi, Rosa Ayesa-Arriola, Nerisa Banaj, Zeynep Başgöze, Jochen Bauer, Karina Blair, Robert James Blair, Katharina Brosch, Yuqi Cheng, Romain Colle, Colm G Connolly, Emmanuelle Corruble, Baptiste Couvy-Duchesne, Benedicto Crespo-Facorro, Kathryn R Cullen, Udo Dannlowski, Christopher G Davey, Katharina Dohm, Janice M Fullerton, Ali Saffet Gonul, Ian H Gotlib, Dominik Grotegerd, Tim Hahn, Ben J Harrison, Mengxin He, Ian B Hickie, Tiffany C Ho, Frank Iorfino, Andreas Jansen, Fabrice Jollant, Tilo Kircher, Bonnie Klimes-Dougan, Melissa Klug, Elisabeth J Leehr, Elizabeth T C Lippard, Katie A Mclaughlin, Susanne Meinert, Adam Bryant Miller, Philip B Mitchell, Benson Mwangi, Igor Nenadić, Amar Ojha, Bronwyn J Overs, Julia-Katharina Pfarr, Fabrizio Piras, Kai G Ringwald, Gloria Roberts, Georg Romer, Marsal Sanches, Margaret A Sheridan, Jair C Soares, Gianfranco Spalletta, Frederike Stein, Giana I Teresi, Diana Tordesillas-Gutiérrez, Aslihan Uyar-Demir, Nic J A Van Der Wee, Steven J Van Der Werff, Robert R J M Vermeiren, Alexandra Winter, Mon-Ju Wu, Tony T Yang, Paul M Thompson, Miguel E Rentería, Neda Jahanshad, Hilary P Blumberg, Anne-Laura Van Harmelen, Enigma Suicidal Thoughts And Behaviours Consortium, Lianne Schmaal

Faculty, Staff and Student Publications

Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample …

Ambulatory Monitoring Of Subglottal Pressure Estimated From Neck-Surface Vibration In Individuals With And Without Voice Disorders, Juan P Cortés, Jon Z Lin, Katherine L Marks, Víctor M Espinoza, Emiro J Ibarra, Matías Zañartu, Robert E Hillman, Daryush D Mehta

Faculty, Staff and Student Publications

The aerodynamic voice assessment of subglottal air pressure can discriminate between speakers with typical voices from patients with voice disorders, with further evidence validating subglottal pressure as a clinical outcome measure. Although estimating subglottal pressure during phonation is an important component of a standard voice assessment, current methods for estimating subglottal pressure rely on non-natural speech tasks in a clinical or laboratory setting. This study reports on the validation of a method for subglottal pressure estimation in individuals with and without voice disorders that can be translated to connected speech to enable the monitoring of vocal function and behavior in …

Risk Factors For Community-Acquired Bacterial Infection Among Young Infants In South Asia: A Longitudinal Cohort Study With Nested Case-Control Analysis, Nicholas E Connor, Mohammad Shahidul Islam, Luke C Mullany, Nong Shang, Zulfiqar A Bhutta, Anita K M Zaidi, Sajid Soofi, Imran Nisar, Pinaki Panigrahi, Kalpana Panigrahi, Radhanath Satpathy, Anuradha Bose, Rita Isaac, Abdullah H Baqui, Dipak K Mitra, Qazi Sadeq-Ur Rahman, Tanvir Hossain, Stephanie J Schrag, Jonas M Winchell, Melissa L Arvay, Maureen H Diaz, Jessica L Waller, Martin W Weber, Davidson H Hamer, Patricia Hibberd, A S M Nawshad Uddin Ahmed, Maksuda Islam, Mohammad Belal Hossain, Shamim A Qazi, Shams El Arifeen, Gary L Darmstadt, Samir K Saha

Faculty, Staff and Student Publications

OBJECTIVE: Risk factors predisposing infants to community-acquired bacterial infections during the first 2 months of life are poorly understood in South Asia. Identifying risk factors for infection could lead to improved preventive measures and antibiotic stewardship.

METHODS: Five sites in Bangladesh, India and Pakistan enrolled mother-child pairs via population-based pregnancy surveillance by community health workers. Medical, sociodemographic and epidemiological risk factor data were collected. Young infants aged 0-59 days with signs of possible serious bacterial infection (pSBI) and age-matched controls provided blood and respiratory specimens that were analysed by blood culture and real-time PCR. These tests were used to build …

Cardiovascular Outcomes In Patients With Chronic Kidney Disease And Covid-19: A Multi-Regional Data-Linkage Study, Emilie J Lambourg, Peter J Gallacher, Robert W Hunter, Moneeza Siddiqui, Eve Miller-Hodges, James D Chalmers, Dan Pugh, Neeraj Dhaun, Samira Bell

Faculty, Staff and Student Publications

BACKGROUND: Data describing cardiovascular outcomes in patients with coronavirus disease 2019 (COVID-19) and chronic kidney disease (CKD) are lacking. We compared cardiovascular outcomes of patients with and without COVID-19, stratified by CKD status.

METHODS: This retrospective, multi-regional data-linkage study utilised individual patient-level data from two Scottish cohorts. All patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Cohort 1 between 1 February 2020 and 31 March 2021 and in Cohort 2 between 28 February 2020 and 8 February 2021 were included.

RESULTS: Overall, 86 964 patients were tested for SARS-CoV-2. There were 36 904 patients (mean±sd age 61±21 …

Identification Of Novel Susceptibility Methylation Loci For Pancreatic Cancer In A Two-Phase Epigenome-Wide Association Study, Ziqiao Wang, Yue Lu, Myriam Fornage, Li Jiao, Jianjun Shen, Donghui Li, Peng Wei

Faculty, Staff and Student Publications

The role of DNA methylation and its interplay with gene expression in the susceptibility to pancreatic cancer (PanC) remains largely unexplored. To fill in this gap, we conducted an integrative two-phase epigenome-wide association study (EWAS) of PanC using genomic DNA from 44 cases and 556 controls (20 local controls and 536 public controls in the Framingham Heart Study) in phase 1 and 23 cases and 22 controls in phase 2. We validated the findings using pre-diagnostic blood samples from 13 cases and 26 controls in the Women's Health Initiative (WHI) Study. We further examined gene expression in peripheral leukocytes of …

Identification Of Key Genes Associated With Cancer Stem Cell Characteristics In Wilms’ Tumor Based On Bioinformatics Analysis, Cheng Su, Jie Zheng, Siyu Chen, Jinwei Tuo, Jinxia Su, Xiuyi Ou, Shaohua Chen, Congjun Wang

Faculty, Staff and Student Publications

BACKGROUND: Nephroblastoma, also known as Wilms' tumor (WT), remains one of the major causes of tumor-related deaths worldwide in children. Cancer stem cells (CSCs) are considered to be the main culprits in cancer resistance and disease recurrence, which are reported in multiple types of tumors. However, the research on CSCs in WT is limited. Therefore, our study aimed to identify the key genes related to CSCs in WT to provide new ideas for treating WT.

METHODS: The RNA-seq and clinical data of WT samples were obtained from the University of California Santa Cruz (UCSC) Xena database, which included 120 WT …

Anatomical Validation Of Automatic Respiratory Motion Correction For Coronary 18f-Sodium Fluoride Positron Emission Tomography By Expert Measurements From Four-Dimensional Computed Tomography, Martin Lyngby Lassen, Evangelos Tzolos, Tinsu Pan, Jacek Kwiecinski, Sebastien Cadet, Damini Dey, Daniel Berman, Piotr Slomka

Faculty, Staff and Student Publications

BACKGROUND: Respiratory motion correction is of importance in studies of coronary plaques employing

PURPOSE: To investigate the accuracy of the motion correction employed in a software (FusionQuant) used for evaluation of

METHODS: This study included 23 patients who undertook thoracic PET scans for the assessment of coronary plaques using

RESULTS: In total, 19 coronary plaques were identified in 16 patients. No statistical differences were observed for the maximum respiratory motion observed in x, y, and the 3D motion fields (magnitude and direction) between the CT and PET (X direction: 4D CT = 2.5 ± 1.5 mm, PET = 2.4 ± …

Bile Acids Regulate The Epithelial Na+ Channel In Native Tissues Through Direct Binding At Multiple Sites, Xue-Ping Wang, Viktor Tomilin, Andrew J Nickerson, Runze Tian, Merve Ertem, Abagail Mckernan, Xiaoguang Lei, Oleh Pochynyuk, Ossama B Kashlan

Faculty, Staff and Student Publications

Bile acids, originally known to emulsify dietary lipids, are now established signalling molecules that regulate physiological processes. Signalling targets several proteins that include the ion channels involved in regulating intestinal motility and bile viscosity. Studies show that bile acids regulate the epithelial sodium channel (ENaC) in cultured cell models and heterologous expression systems. ENaC plays both local and systemic roles in regulating extracellular fluids. Here we investigated whether bile acids regulate ENaC expressed in native tissues. We found that taurocholic acid and taurohyodeoxycholic acid regulated ENaC in both the distal nephron and distal colon. We also tested the hypothesis that …

Netie: Inferring The Evolution Of Neoantigen-T Cell Interactions In Tumors, Tianshi Lu, Seongoh Park, Yi Han, Yunguan Wang, Shawna Marie Hubert, P Andy Futreal, Ignacio Wistuba, John V Heymach, Alexandre Reuben, Jianjun Zhang, Tao Wang

Faculty, Staff and Student Publications

Neoantigens are the key targets of antitumor immune responses from cytotoxic T cells and play a critical role in affecting tumor progressions and immunotherapy treatment responses. However, little is known about how the interaction between neoantigens and T cells ultimately affects the evolution of cancerous masses. Here, we develop a hierarchical Bayesian model, named neoantigen-T cell interaction estimation (netie) to infer the history of neoantigen-CD8

International Delphi Consensus Guidelines For Follow-Up After Prophylactic Total Gastrectomy: The Life After Prophylactic Total Gastrectomy (Lag-Tg) Study, Geoffrey Roberts, Patrick R Benusiglio, Tanya Bisseling, Daniel Coit, Jeremy L Davis, Sam Grimes, Theresa A Guise, Richard Hardwick, Kirsty Harris, Paul Furman Mansfield, Jeremy Rossaak, Karen Chelcun Schreiber, Peter P Stanich, Vivian E Strong, Pardeep Kaurah

Faculty, Staff and Student Publications

BACKGROUND: Prophylactic total gastrectomy (PTG) remains the only means of preventing gastric cancer for people with genetic mutations predisposing to Hereditary Diffuse Gastric Cancer (HDGC), mainly in the CDH1 gene. The small but growing cohort of people undergoing PTG at a young age are expected to have a life-expectancy close to the general population, however, knowledge of the long-term effects of, and monitoring requirements after, PTG is limited. This study aims to define the standard of care for follow-up after PTG.

METHODS: Through a combination of literature review and two-round Delphi consensus of major HDGC/PTG units and physicians, and patient …

Immune Dysfunction Signatures Predict Outcomes And Define Checkpoint Blockade-Unresponsive Microenvironments In Acute Myeloid Leukemia, Sergio Rutella, Jayakumar Vadakekolathu, Francesco Mazziotta, Stephen Reeder, Tung-On Yau, Rupkatha Mukhopadhyay, Benjamin Dickins, Heidi Altmann, Michael Kramer, Hanna A Knaus, Bruce R Blazar, Vedran Radojcic, Joshua F Zeidner, Andrea Arruda, Bofei Wang, Hussein A Abbas, Mark D Minden, Sarah K Tasian, Martin Bornhäuser, Ivana Gojo, Leo Luznik

Faculty, Staff and Student Publications

Background

Immune exhaustion and senescence are dominant dysfunctional states of effector T cells and major hurdles for the success of cancer immunotherapy. In the current study, we characterized how acute myeloid leukemia (AML) promotes the generation of senescent-like CD8⁺ T cells and whether they have prognostic relevance.

METHODS

We analyzed NanoString, bulk RNA-Seq and single-cell RNA-Seq data from independent clinical cohorts comprising 1,896 patients treated with chemotherapy and/or immune checkpoint blockade (ICB).

Results

We show that senescent-like bone marrow CD8⁺ T cells were impaired in killing autologous AML blasts and that their proportion negatively correlated with overall survival …