Medicine and Health Sciences Commons^™

Declaring Futility After Traumatic Injury And The Burden Of Failure On The Surgeon, Jan-Michael Van Gent, Bryan A Cotton

Faculty, Staff and Student Publications

In this edition of the THOR supplement in Transfusion, there are two articles that deal with resuscitation futility and transfusion. In one article, Yazer et al. delve into the details of the studies outlined in this editorial and summarize the literature on the topic of transfusion and futility. The second article by Dr. Jay Malone discusses the ethical issues surrounding massive transfusion and resuscitation. Taken together, these articles address the clinical and ethical issues surrounding this very emotive and difficult topic.

The Impact Of Rapid Infusers On The Hemostatic Potential Of Cryoprecipitate Products, Connor D Purvis, Samantha Redden, Andrew Jacobson, Yao-Wei Wang, Julie Campbell, Jessica Cardenas, Jan-Michael Van Gent, Bryan A Cotton

Faculty, Staff and Student Publications

Background: In cases of massive transfusion, intravenous access can be limited. Additionally, delivering different products through separate lines and infusion methods adds unnecessary steps. RBC, plasma, and whole blood (WB) are delivered via rapid infusers; cryoprecipitate (CRYO) is infused through separate access and is not approved with these devices.

Study design and methods: We examined the impact of different transfusion methods on hemostatic performance and factor activity using two available CRYO products. Ten bags of CRYO, ten bags pathogen-reduced CRYO (Intercept® Fibrinogen Complex, IFC), and 20 units of WB were obtained. Each CRYO bag was infused with one unit of …

Estrogen As A Therapeutic Agent: Targeting Endotheliopathy And Coagulopathy In Trauma, Niruktha Raghavan, Mira Patel, Bryan A Cotton, Julia Coleman, Donald Jenkins

Faculty, Staff and Student Publications

Background: Traumatic injury remains a leading cause of death, often due to uncontrolled hemorrhage and trauma-induced coagulopathy (TIC). TIC is critically triggered by the endotheliopathy of trauma, involving endothelial cell injury and glycocalyx degradation. Despite conventional advances, the stable casualty rate underscores the urgent need for new precision resuscitation strategies that acknowledge factors like biological sex.

Design: The central hypothesis is that estrogen confers a survival advantage in hormonally active females through a dual action: endothelial cell stabilization (halting glycocalyx shedding) and its inherent procoagulant effect. The analysis assesses the therapeutic potential of both exogenous estrogen and female-derived blood products …

A Rare Case Of Gastric Ascariasis, Sharon Pan, Kevin Yu, Blaine A Mathison, Yan Gao, Marc Roger Couturier, Salem Muayad, Violeta Chávez, Ranya Selim

Faculty, Staff and Student Publications

Background: Ascariasis, caused by the parasitic roundworm Ascaris lumbricoides, is one of the most common helminthic infections globally. Spread by contaminated soil through the fecal-oral route, A. lumbricoides typically infects the small intestine and has rarely been reported to infect the stomach.

Case summary: We describe an unusual case of a male in his 30s with a history of neuroendocrine tumor (NET) who immigrated from Colombia and who underwent esophagogastroduodenoscopy (EGD) and colonoscopy for further evaluation of abdominal pain. He was incidentally found to have a female Ascaris worm in his stomach that was retrieved during the EGD.

Conclusion: …

Dolutegravir Developmental Toxicity Is Mitigated By Magnesium And Folate In Zebrafish Embryos, Robert M Cabrera, Ahmed Mohamed, Ryoko Minowa, Katheryn A Neugebauer, Daniel A Gorelick

Faculty, Staff and Students Publications

Integrase strand transfer inhibitors have transformed human immunodeficiency virus (HIV) therapy, yet the widely prescribed drug dolutegravir (DTG) has been linked to developmental toxicity, and its teratogenic mechanism remains unclear. Here, we used zebrafish to dissect DTG toxicity during early vertebrate development. DTG exposure from 2-4 h post-fertilization (hpf) to 24 hpf produced high mortality and abnormal morphology. Co-treatment with folates partially restored normal morphology, whereas calcium had no effect. Strikingly, supplementation with magnesium (Mg) partially rescued DTG-exposed embryos, implicating Mg availability in protection. In competitive binding assays, Mg increased binding of folate to purified folate receptor (FOLR1) by 30% …

Validation Of The German Version Of The Movement Disorder Society Non-Motor Scale (Mds-Nms), Jonas Bendig, Anika Frank, Adrianna Lipska-Dieck, Kristof Wunderlich, David Geißler-Lösch, Isabel Wurster, Roswitha Kemmner, Kathrin Brockmann, Sheng Luo, Christopher G Goetz, Glenn T Stebbins, Pablo Martinez-Martin, Tiago A Mestre, Alvaro Sanchez-Ferro, Monica M Kurtis, Michelle H S Tosin, Roberta Balestrino, Chi-Ying R Lin, Carmen Gasca-Salas, Heinz Reichmann, Bjoern H Falkenburger

Faculty, Staff and Students Publications

No abstract provided.

Assessment Of Correctness, Content Omission, And Risk Of Harm In Large Language Model Responses To Ophthalmology Continuing Medical Education Questions, Jacqueline L Chen, Amanda J Lu, Rohan Verma, Li Wang, Douglas D Koch, Allison J Chen

Faculty, Staff and Students Publications

Purpose: To evaluate the accuracy and prose responses of 2 large language models (LLMs) to ophthalmology continuing medical education questions.

Design: Question prompts and multiple choice (MC) answer options were input into the 2 LLMs, and responses were analyzed for accuracy and assessed for evidence of correctness, completeness, bias, and potential harm using a previously reported standardized rubric.

Subjects: Basic and Clinical Science Course questions and MC answer options from the American Academy of Ophthalmology question bank were used as inputs into the 2 LLMs (ChatGPT-4 and Google Vertex's Gemini Pro 1.5).

Methods: The MC responses were assessed for accuracy …

Novel Model To Predict Survival In Dcd Heart Transplants: Development Of A Mortality Risk Score Using Unos Data, Anh Nguyen, Abbas Rana, Alexis Shafii, Gabriel Loor, Andrew Civitello, Todd Rosengart, Kenneth Liao

Faculty, Staff and Students Publications

Background: While prior studies have compared outcomes between donation after brain death (DBD) and donation after circulatory death (DCD) heart transplants, this study focuses on donor and recipient characteristics influencing survival and develop a risk score exclusively in DCD heart transplants.

Methods: We analyzed adult DCD heart transplants in the UNOS database from January 2019 to June 2024. Mortality risk factors were assessed using multivariable Cox proportional hazards regression. The coefficients of the most significant factors were used to develop a mortality risk score.

Results: Among 18,014 adult heart transplants, 1453 (8.1%) were DCD recipients. One-, two-, and three-year survival …

The Impact Of Tracheal Intubation Attempts On Chest Compression Fraction During Pediatric Cpr: A Report From The Videography In Pediatric Resuscitation (Viper) Collaborative, Theerapon Jariyasakoolroj, Karen O'Connell, Thomas Macdonald, John Breslin, Jennifer Murphy, Crystal Macdonald, Tara Neubrand, Laura Rochford, Sage Myers, Benjamin Kerrey, Aaron Donoghue

Faculty, Staff and Students Publications

Aim: To examine the association between tracheal intubation (TI) attempts and chest compression (CC) pauses on chest compression fraction (CCF) during pediatric CPR across a network of emergency departments.

Methods: Prospective observational cohort by the Videography in Pediatric Resuscitation (VIPER) Collaborative. Videorecorded CPR events were reviewed to measure CC pauses and characterize TI attempts. CCF was calculated as the proportion of time compressions were delivered during each event. Events were categorized based on whether TI-associated pauses occurred, and CCF was compared using Wilcoxon rank-sum testing.

Results: A total of 183 CPR events were included. The median event duration was 971 …

Hepatopulmonary Syndrome As Presentation Of Pediatric Metabolic Dysfunction-Associated Steatohepatitis, Shruti Sakhuja, Stacey S Beer, Kalyani R Patel, Alexiss M Williams, Nhu Thao Galvan, John A Goss, Krupa R Mysore

Faculty, Staff and Students Publications

Childhood obesity is rising and leading to serious co-morbidities, among which is metabolic dysfunction-associated steatotic liver disease (MASLD) predisposing individuals to cirrhosis. We describe a young 11-year-old Hispanic male who presented with hepatopulmonary syndrome secondary to cirrhotic portal hypertension from metabolic dysfunction-associated steatohepatitis (MASH), necessitating liver transplantation. Despite lifestyle modifications post-transplantation, the patient experienced persistent weight gain and recurrence of steatosis, emphasizing challenges of managing pediatric MASLD. The burden of childhood obesity is increasing and impacting children significantly earlier than previously believed. Our case is one of the few to report the severe complications of MASH in a young, pre-teen …

Hiding In Plain Sight: A Call To Prevent Cutaneous Leishmaniasis Transmission In The United States, Juan David Ramírez, Sarah M Gunter, Megan Coffee, Norman Beatty, Dawn M Wetzel

Faculty, Staff and Students Publications

Cutaneous leishmaniasis (CL), once considered a travel-associated tropical disease, is increasingly transmitted within the United States, particularly in southern regions. Despite mounting evidence of local transmission, public health recognition and preventive infrastructure remain limited. This Viewpoint highlights the urgent need to shift the U.S. CL response from questioning endemicity to preventing transmission. We review ecological, clinical, and surveillance data demonstrating the presence of competent vectors, animal reservoirs, and autochthonous human cases. Diagnostic delays, underreporting, and insufficient provider training contribute to missed prevention opportunities. Climate change and peri-urban rodent-human contact data further heighten future risk. A coordinated response is essential, including …

Seroprevalence Of Helicobacter Pylori Infection Among Asymptomatic Patients Served By A Safety-Net Healthcare System, Aaron P Thrift, Peyman Dinarvand, Luis Juarez, Jourdan Brown, Daniel Avila, Jennifer Mistica Zafiro Garcia-Villanueva, Lisa C Danek, Hammad Mahmood, Thomas Porter, Ann Gotschall, Noreen F Pirzada, Jaime J Rueda, Lee B Lu, Afroze Ali, Ijeoma Anyakorah, Sanjana J Bhattarai, Anees Fatima, Jessica Garcia, Hung V Nguyen, Bharat Joshi, Malvika Juneja, Misba S Lateef, Najda Mujtaba, Preethi V Nambi, Jay S Orr, Huma Rahman, Stephanie Nguyen, Amna Waqar, Yanyan Chen, David Y Graham, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

Background & aims: Helicobacter pylori screening and eradication is a cost-effective strategy for primary gastric cancer prevention in high-risk populations outside the United States. There is a paucity of population-based H pylori seroprevalence data available in high-risk U.S. groups, particularly data for low-income, uninsured patient populations.

Methods: We used data from a cross-sectional study of a largely underserved, immigrant, and minority patient population. Inclusion criteria included asymptomatic individuals 30-65 years of age without prior H pylori testing or treatment. Consented patients completed a study survey and a blood draw to screen for H pylori using IgG serology. We calculated seroprevalence …

Survodutide For The Treatment Of Obesity: Baseline Characteristics Of The Synchronize Cardiovascular Outcomes Trial, Elke Platz, Lee M Kaplan, Carel W Le Roux, Sean Wharton, Svenja Burger, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Constanze Fey, Mikhail N Kosiborod, Biykem Bozkurt

Faculty, Staff and Students Publications

No abstract provided.

A Smoking-Related Plasma Protein Score And Smoking-Related Cancer Risk And Mortality In The Atherosclerosis Risk In Communities Study, Meng Ru, Christopher Douville, Aghiles Guenoun, Hana Zahed, Christie M Ballantyne, Kenneth R Butler, Josef Coresh, David J Couper, Panagis Galiatsatos, Marc J Gunter, Ron C Hoogeveen, Mattias Johansson, Corinne E Joshu, P Martijn Kolijn, Christina M Lill, Jiayun Lu, Michael T Marrone, Giovanna Masala, David C Muller, Anna E Prizment, Raul Zamora-Ros, Nilanjan Chatterjee, Adrienne Tin, Elizabeth A Platz

Faculty, Staff and Students Publications

Background: Self-reported smoking may not fully capture individualized risk of smoking-related cancer, but circulating proteins may reflect biological consequences of smoking. Thus, we developed a score based on smoking-related proteins and evaluated its association with smoking-related cancer.

Methods: This prospective cohort study included 10 563 participants aged 47-70 years in the Atherosclerosis Risk in Communities study. Plasma proteins were measured using the SomaScan Platform (SomaLogic Operating Co, Inc). The score was constructed from proteins associated with current smoking, pack-years, or recent quitting identified by linear regression and elastic net regression. Cox regression was used to estimate adjusted hazard ratios and …

Plasma Metabolites After 10-Weeks Of Glucose Vs Fructose-Sweetened Beverages In Subjects With Overweight/Obesity, Mélanie Guirette, Danielle E Haslam, Jiantao Ma, Peter J Havel, Kimber L Stanhope, Olga Ilkayeva, Christopher B Newgard, Nicola M Mckeown, Mark A Herman

Faculty, Staff and Students Publications

To identify metabolites as potential biomarkers of fructose vs glucose consumption and related metabolic changes, we conducted exploratory metabolomic profiling of fasting blood samples from participants in a double-blind, parallel-arm trial involving 31 male and female adults with overweight or obesity, both before and after supplementation with glucose- or fructose-sweetened beverages. Orthogonal Partial Least Square Discriminatory Analysis (OPLS-DA) was used to identify metabolites that could discriminate between the 2 intervention groups. Changes in 16 metabolites (5 of which are branched-chain amino acid catabolic pathway metabolites) and the branched chain keto acid (BCKA) composite score showed nominal (FDR adjusted P-value …

Risk Factors When Considering Heart Transplants With Donors Aged 45 Or Above: Development Of A Novel Mortality Risk Score Using Unos Data, Anh Nguyen, Abbas Rana, Alexis Shafii, Gabriel Loor, Andrew Civitello, Todd Rosengart, Kenneth Liao

Faculty, Staff and Students Publications

Background: Current International Society for Heart and Lung Transplantation guidelines support the use of donor hearts aged ≥45 if significant coronary artery disease is excluded and ischemic time remains < 4 hours. This study aimed to identify additional risk factors affecting patient survival and develop a risk score for recipients of older donor hearts.

Methods: We performed a retrospective cohort study of adult heart transplants using donors aged ≥45 from January 2000 to June 2024, using United Network for Organ Sharing data. Multivariable Cox regression identified risk factors for mortality, and the most significant variables were used to construct a risk score.

Results: Of 58,859 adult heart transplants, 9,843 (16.7%) involved donors aged ≥45. Recipient median age was 58 years (interquartile range, 51-64). One-, 5-, …

Congenital Aromatase Deficiency In An Adult Male: A Case Report Of Clinical Course And Symptom Reversal With Estrogen Supplementation, Peyton Coady, Arnaav Walia, Beatriz Hernandez, David E Hinojosa-Gonzalez, Adnan El-Achkar, Mohit Khera

Faculty, Staff and Students Publications

Congenital aromatase deficiency is an autosomal recessive CYP19A1 loss-of-function disorder that blocks conversion of androgens to estrogens. A man with homozygous CYP19A1 c.628G > A (exon 5) presented with longstanding fatigue, low libido, and desire to maintain fertility. Physiologic estrogen replacement was started with transdermal estradiol 0.0375 mg. After three months of estrogen therapy, the patient reported markedly improved energy and libido. Follow-up evaluation showed a rise in serum estradiol with normalization of gonadotropins, while maintaining spermatogenesis. This case illustrates the essential role of estrogen in male physiology, sexual function, and fertility. Estradiol replacement can alleviate hypoestrogenic symptoms with preservation of …

Plasma Proteins Associated With Psychosocial Factors And Heart Disease: The Jackson Heart Study, Sara N O'Brien, Madeline G Gillman, Michael D Green, Daniel E Cruz, James S Floyd, Susan Hankinson, Daniel H Katz, Xiaojuan Liu, Michelle C Odden, Bruce M Psaty, Alexander P Reiner, Jerome I Rotter, Stephen S Rich, Robert E Gerszten, Amil Shah, Mario Sims, Usman A Tahir, Lesley F Tinker, Alexis C Wood, Bing Yu, Anthony S Zannas, Laura M Raffield, Láshauntá M Glover

Faculty, Staff and Students Publications

Background: Knowledge of proteomic mechanisms explaining the link between psychosocial stress and cardiovascular disease is limited. This study aimed to (1) identify plasma proteins associated with psychosocial factors and (2) assess associational pathways between psychosocial factors, identified proteins, and incident cardiovascular disease events in a discovery cohort, JHS (Jackson Heart Study), and 2 replication cohorts, the CHS (Cardiovascular Health Study), and the MESA (Multi-Ethnic Study of Atherosclerosis).

Methods: JHS participants from exam 1 (2000-2004) with SomaScan 1.3k platform proteomics data were included (n=2143, mean age=55.3). Depressive symptoms and perceived stress scores were measured via the 20-item Center for Epidemiological Studies …

Ixodid And Flea Infestations And Associated Bacteria On Two Sympatric Felid Species In South Texas, Allan T Showler, Hilary Swarts, Maya Murry, Alisa Nelson, Alexander R Kneubehl, Sarah M Gunter

Faculty, Staff and Students Publications

Ixodid ticks and fleas parasitize wild felids and can transmit pathogens of veterinary and public health concern. We identified ixodid and flea species collected from sympatric South Texas bobcats, L. rufus, and ocelots, L. pardalis. Greater diversities of ixodids were found on both felids than in previous reports, with seven species in three genera on L. rufus and six species in three genera on L. pardalis. We report first findings of tropical horse tick, Dermacentor nitens, on L. rufus in Texas, and Ixodes keiransi on both felids in Texas. Although false cayenne tick, Amblyomma tenellum, nymphs were the most abundant …

Stance And Gait Analysis Of Apollo Astronauts On The Moon, Faye Y Chiou-Tan, Conrad Li, Jason P Caffrey, Millard Reschke, Timothy R Macaulay

Faculty, Staff and Students Publications

Introduction/aim: As humans return to the Moon, safe efficient ambulation and fall prevention on the lunar surface are key concerns. The analysis of gait from archived Apollo mission video footage is now possible with pose estimation video analysis software. Thus, this study aims to retrospectively quantify parameters of Apollo astronauts' stance and gait on the Moon.

Methods: Publicly available National Aeronautics and Space Administration (NASA) footage of astronauts ambulating on the Lunar surface was examined using body pose analysis software. Goniometric lower limb joint/torso angles and width of base of stance and gait were derived. Gait cycle stance phase, swing …

Bridging Access Gaps In Radiotherapy: Knowledge-Based Planning In A Resource-Constrained Clinical Setting, Milton E Ixquiac Cabrera, Erick O Montenegro, Matthew Schmidt, Baozhou Sun, James A Kavanaugh, Taoran Li, Angel Velarde, Vicky De Falla, Francisco Reynoso

Faculty, Staff and Students Publications

Background/purpose: Radiotherapy access in low- and middle-income countries (LMICs) is severely limited by shortages of trained personnel, high patient volumes, and large waiting times for manual treatment planning. Knowledge-based planning (KBP) has shown promise in high-income settings, yet its feasibility in resource-constrained environments remains underexplored. This study aimed to evaluate the feasibility of adapting a KBP model developed at a high-income institution for clinical use at Liga Nacional Contra el Cáncer (LNCC) in Guatemala for gynecological radiotherapy planning.

Materials and methods: A RapidPlan KBP model (Varian-Siemens Healthineers, Palo Alto, CA, USA) originally developed at Washington University in St. Louis using …

A Multi-Institutional Epid-Based 3d Dose Reconstruction Model In A Virtual Phantom For Standardized Patient Qa, Benchmarking And Auditing For Stereotactic Radiosurgery, Benjamin Zwan, Emily Searle, Cameron Stanton, Ching-Ling Teng, Seng Boh Lim, Andrew Dipuglia, Richard Popple, Michael Lovelock, Ashley Cullen, Conor K Mcgarry, Victoria Robinson, Sergei Zavgorodni, Baozhou Sun, Xiaodong Zhao, Matthew Schmidt, Juan-Francisco Calvo-Ortega, Gemma Warner, Andrew Cousins, Michael Barnes, Peter Greer

Faculty, Staff and Students Publications

Background and purpose: For single-isocentre multi-target (SIMT) stereotactic radiosurgery (SRS), benchmarking, auditing and inter-institutional standardisation of dose verification remain challenging as they require specialized equipment and expertise. This work aims to develop and validate an electronic portal imaging device (EPID)-based technique to determine 3D dose in a virtual spherical phantom which is applicable across institutions for SIMT SRS dose verification.

Materials and methods: Small-field output factors from 11 international centres were measured in-water for the TrueBeam linear accelerator, including jaw-defined and high-definition multi-leaf collimator (MLC) fields from 0.5 × 0.5 to 20 × 20 cm2 and depths from 1.5-20 cm. …

The "Hallett Sign" Of Functional Jerky Movement Disorder, Jon Stone, Anthony E Lang, Joseph Jankovic, Michele Tinazzi, Barbara A Dworetzky, Alan Carson, Marina A J Tijssen

Faculty, Staff and Students Publications

No abstract provided.

Adhesion G Protein-Coupled Receptors, Tobias Langenhan, Garret R Anderson, Demet Araç, Gabriela Aust, Monserrat Avila-Zozaya, Sofie Morsing Bagger, Patrick Barth, Sandra Berndt, Stephen C Blacklow, Beatriz Blanco-Redondo, Antony A Boucard, James P Bridges, Lara-Sophie Brodmerkel, Kathleen M Caron, Yin Kwan Chung, Andrew N Dates, Virginea De Araujo Farias, Daniel Del Toro, Joseph G Duman, Felix B Engel, David M Favara, Caroline J Formstone, Chaoyu Fu, Alain Garcia De Las Bayonas, Anastasia Georgiadi, David E Gloriam, Randy A Hall, Jörg Hamann, Peter W Hildebrand, Cheng-Chih Hsiao, Bill X Huang, Jonathan A Javitch, Hee-Yong Kim, Robert J Kittel, Gunnar Kleinau, Richard Leduc, Ines Liebscher, Hsi-Hsien Lin, Joshua Linnert, Marie-Gabrielle Ludwig, David C Martinelli, Signe Mathiasen, Daniel Matúš, Mariam Melkumyan, Ana L Moreno-Salinas, Jan Mulder, Michael A Nash, Kasturi Pal, Daniel T Pederick, Nicole A Perry-Hauser, Xianhua Piao, Yu-Qi Ping, Dimitris G Placantonakis, Fabian Pohl, Simone Prömel, Mette M Rosenkilde, Laurent Sabbagh, Richard C Sando, Patrick Scheerer, Torsten Schöneberg, Elena Seiradake, Mareike Selcho, Florian Seufert, Abhishek K Singh, Georgios Skiniotis, Katja Spiess, Norbert Sträter, David Strutt, Thomas C Südhof, Jinpeng Sun, Gregory G Tall, Doreen Thor, Douglas G Tilley, Kimberley F Tolias, Mario Vallon, Erwin G Van Meir, Benoit Vanhollebeke, Giselle R Wiggin, Uwe Wolfrum, Jie Yan, Nathan A Zaidman, Yimin Zou, Nicole Scholz

Faculty, Staff and Students Publications

Adhesion G protein-coupled receptors (aGPCRs) constitute a structurally and functionally distinct group within the superfamily of GPCRs. In 2015, the International Union of Pharmacology invited the Adhesion GPCR Consortium to publish a comprehensive review about aGPCRs and establish a unified nomenclature. Since then, substantial progress has been made in delineating the biological roles, molecular architecture, biochemical properties, expression profiles, ligand repertoire, and activation and signaling strategies of aGPCRs. Commensurate with these advances, their relevance to human pathophysiology has become increasingly apparent. In a coordinated effort, the Adhesion GPCR Consortium has reviewed recent progress in this field and provides a comprehensive …

Adhesion G Protein-Coupled Receptors, Tobias Langenhan, Garret R Anderson, Demet Araç, Gabriela Aust, Monserrat Avila-Zozaya, Sofie Morsing Bagger, Patrick Barth, Sandra Berndt, Stephen C Blacklow, Beatriz Blanco-Redondo, Antony A Boucard, James P Bridges, Lara-Sophie Brodmerkel, Kathleen M Caron, Yin Kwan Chung, Andrew N Dates, Virginea De Araujo Farias, Daniel Del Toro, Joseph G Duman, Felix B Engel, David M Favara, Caroline J Formstone, Chaoyu Fu, Alain Garcia De Las Bayonas, Anastasia Georgiadi, David E Gloriam, Randy A Hall, Jörg Hamann, Peter W Hildebrand, Cheng-Chih Hsiao, Bill X Huang, Jonathan A Javitch, Hee-Yong Kim, Robert J Kittel, Gunnar Kleinau, Richard Leduc, Ines Liebscher, Hsi-Hsien Lin, Joshua Linnert, Marie-Gabrielle Ludwig, David C Martinelli, Signe Mathiasen, Daniel Matúš, Mariam Melkumyan, Ana L Moreno-Salinas, Jan Mulder, Michael A Nash, Kasturi Pal, Daniel T Pederick, Nicole A Perry-Hauser, Xianhua Piao, Yu-Qi Ping, Dimitris G Placantonakis, Fabian Pohl, Simone Prömel, Mette M Rosenkilde, Laurent Sabbagh, Richard C Sando, Patrick Scheerer, Torsten Schöneberg, Elena Seiradake, Mareike Selcho, Florian Seufert, Abhishek K Singh, Georgios Skiniotis, Katja Spiess, Norbert Sträter, David Strutt, Thomas C Südhof, Jinpeng Sun, Gregory G Tall, Doreen Thor, Douglas G Tilley, Kimberley F Tolias, Mario Vallon, Erwin G Van Meir, Benoit Vanhollebeke, Giselle R Wiggin, Uwe Wolfrum, Jie Yan, Nathan A Zaidman, Yimin Zou, Nicole Scholz

Faculty, Staff and Students Publications

Adhesion G protein-coupled receptors (aGPCRs) constitute a structurally and functionally distinct group within the superfamily of GPCRs. In 2015, the International Union of Pharmacology invited the Adhesion GPCR Consortium to publish a comprehensive review about aGPCRs and establish a unified nomenclature. Since then, substantial progress has been made in delineating the biological roles, molecular architecture, biochemical properties, expression profiles, ligand repertoire, and activation and signaling strategies of aGPCRs. Commensurate with these advances, their relevance to human pathophysiology has become increasingly apparent. In a coordinated effort, the Adhesion GPCR Consortium has reviewed recent progress in this field and provides a comprehensive …

Mif-Cd74 Signaling Drives Immune Modulation In Medulloblastoma, Benjamin Draper, Zhen You, Dean Thompson, Xu Guo, Alaide Morcavallo, Diego Chillon Pino, Carlos Lorenzo Gido Nery, Sumana Shrestha, Chantelle E Bowers, Courtney Himsworth, Alberto Delaidelli, Bethany Remeniuk, Sonia Morlando, Brandon Wade, Freya Gordon, Yara Sanchez-Corrales, Bei Hopkins, Natalie Monteiro, Darren Locke, Miao Liu, Jacob Torrejon Diaz, Kevin Greenslade, Barbara Martins Da Costa, Karen Barker, Colin Kwok, Olumide Ogunbiyi, Anya Fletcher, Stacey Richardson, Carlos Custodia, Rafael Roque, Thomas Jackson, Regan Barfoot, Sergi Castellano, Rebecca M Hill, Olivier Saulnier, Thomas S Jacques, Michael D Taylor, Claudia C Faria, Olivier Ayrault, Poul H Sorensen, John Anderson, Louis Chesler, L Frank Huang, Steven C Clifford, Laura K Donovan

Faculty, Staff and Students Publications

Background: Relapsed medulloblastoma remains a significant therapeutic challenge as it is near universally fatal. The tumor microenvironment of medulloblastoma plays a critical role in tumor progression, influencing tumor growth, immune evasion, and therapeutic resistance. We hypothesized that defining tumor-immune interactions in diagnostic and relapsed medulloblastoma may uncover mechanisms of immune evasion and identify novel therapeutic targets.

Methods: We analyzed paired primary and recurrent RNA-sequencing data from 140 medulloblastoma patients to profile immune cell composition and validate spatial relationships within the TME. To identify key tumor-immune interactions, we developed a novel algorithm to detect receptor-ligand pairs using single-cell RNA-sequencing data. These …

Robot-Assisted Resection Of Diaphragmatic And Hepatorenal Recess Peritoneal Endometriosis: Two Cases And A Narrative Review, Xiaoming Guan, Qiannan Yang, Daniel Y Lovell, Chunhua Zhang

Faculty, Staff and Students Publications

In this report, we describe two cases of diaphragmatic endometriosis with concurrent hepatorenal recess peritoneal involvement managed using robotic-assisted laparoscopic surgery with the da Vinci Xi platform. In both patients, diaphragmatic implants and hepatorenal recess peritoneal lesions were excised en bloc, followed by resection of additional pelvic and abdominal lesions. Case 1 involved a 45-year-old woman whose pathology confirmed endometriosis in 28 of 46 sites, including the diaphragm, umbilicus, bowel, hepatorenal recess peritoneum, and pelvic peritoneum. Case 2 involved a 32-year-old woman with histopathologic evidence of endometriosis in 26 of 34 resected sites, including the appendix, diaphragm, hepatorenal recess peritoneum, …

Reducing Transfusions In Neuromuscular Spinal Fusion: A National Surgical Quality Improvement Program-Pediatrics Quality Improvement Project, Holden Archer, Venessa L Pinto, Farrah Russell, Valentina Briceño, Melissa Ard, Lisa Hensch, Jun Teruya, Tanisha G Daugherty, Wallis Molchen, Ryan D Coleman, Darrell Hanson, Frank T Gerow, Nicole I Montgomery

Faculty, Staff and Students Publications

Background: Pediatric spinal fusion can result in substantial blood loss, particularly in patients with scoliosis related to underlying neuromuscular (NM) disease. Transfusion is frequently required but carries risks including transfusion reactions, alloimmunization, volume overload, and infection.

Local problem: The American College of Surgeons National Surgical Quality Improvement Program-Pediatrics (ACS NSQIP-P) is a nationally validated, risk-adjusted national outcomes registry. At our institution, ACS NSQIP-P data identified our institution as a high outlier in transfusion for neuromuscular scoliosis patients.

Methods: A multidisciplinary group convened from January 2024 to June 2024 to design and implement a perioperative pathway with the primary goal of …

Noncanonical Clock Regulators Control Stress Responses In Digestive Diseases, Dishu Zhou, Roberto E López-Valiente, Samer G Mattar, Dongyin Guan

Faculty, Staff and Students Publications

The digestive system is essential for nutrient absorption, processing, and waste elimination. The expression of many genes and physiological processes within this system exhibits a 24-h rhythmicity. However, modern lifestyle factors, such as jet lag, shift work, and irregular eating patterns, significantly disrupt these rhythms, triggering various stress responses and contributing to numerous digestive disorders. Here, we focus on emerging studies on noncanonical clock regulators involved in stress responses, integrate these novel findings into the established model of the core circadian clock, and highlight recent advances in the development of novel therapeutics targeting these 24-h regulators. In addition, we discuss …

High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology Of Lung Cancer Consortium, Yanhong Liu, Yafang Li, Jinyoung Byun, Vikram R Shaw, Claudio Pikielny, Bo Peng, Chao Cheng, Spiridon Tsavachidis, Xiangjun Xiao, Dakai Zhu, Younghun Han, Ivan P Gorlov, Olga Y Gorlova, Michael Cole, Colette R Gaba, Erin L Crawford, Kristen Purrington, Ellen L Goode, Ping Yang, James Mckay, John K Field, Geoffrey Liu, Rayjean J Hung, Jun Xia, Jiyeon Choi, Matthew B Schabath, Jaclyn Lopiccolo, David C Christiani, Joan Bailey-Wilson, Ann G Schwartz, James C Willey, Diptasri Mandal, Susan M Pinney, Christopher I Amos

Faculty, Staff and Students Publications

Introduction: Rare, deleterious germline variants are key contributors to inherited lung cancer (LC) risk. The Genetic Epidemiology of LC Consortium (GELCC) has curated valuable high-risk LC families and is uniquely positioned to uncover rare, high-penetrance variants underlying familial LC (FLC).

Methods: We performed whole-genome and exome sequencing on germline DNA from 120 high-risk LC families (177 FLC cases, 309 unaffected relatives). We prioritized rare (allele frequency < 1% in the genome aggregation database), potentially deleterious variants present in two or more FLC cases. These variants were then validated in 10,085 sporadic LC (SLC) cases and 612,970 controls.

Results: We identified 118 candidate variants, 28 of which were validated in SLC with strong statistical support. We discovered a novel pathogenic axis of three truncating variants in GALNT6, MUC4, and ERBB3 genes, which …