Medical Sciences Commons^™

Deep Brain Stimulation Response Circuits In Obsessive-Compulsive Disorder, Andreas Horn, Ningfei Li, Garance M Meyer, Ron Gadot, Nicole R Provenza, Sameer A Sheth

Faculty, Staff and Students Publications

In the field of deep brain stimulation (DBS), two major themes are currently making significant progress. First, the framework of connectomic DBS, in which circuits that are associated with improvements of specific symptoms are described and targeted to improve and potentially personalize treatment. Second, the concept of brain sensing and adaptive DBS, which aims at identifying neural biomarkers that may guide stimulation in a closed-loop fashion.

In DBS for Obsessive Compulsive Disorder (OCD), substantial progress has been made on both ends, over the last five years. Together, results begin to draw a picture of exactly which circuit is …

Integrated Transcriptomic Landscape Of Medulloblastoma And Ependymoma Reveals Novel Tumor Subtype-Specific Biology, Sonali Arora, Nicholas Nuechterlein, Matt Jensen, Gregory Glatzer, Philipp Sievers, Srinidhi Varadharajan, Andrey Korshunov, Felix Sahm, Stephen C Mack, Michael D Taylor, Taranjit S Gujral, Eric C Holland

Faculty, Staff and Students Publications

Background: Medulloblastoma and ependymoma are common pediatric central nervous system tumors with significant molecular and clinical heterogeneity. While molecular subgrouping has enabled classification into molecular subtypes, the extent of heterogeneity within these subgroups remains poorly defined.

Methods: We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. After rigorous batch effect correction, normalization, and dimensionality reduction, we generated a unified landscape to explore gene expression, signaling pathways, RNA fusions, and copy number variations.

Results: Our transcriptional analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with …

Analysis Of Failure To Rescue In Adult Patients Who Undergo Open, Proximal Aortic Repair, Kyle W Blackburn, Joseph S Coselli, Armin Farazdaghi, Lynna Nguyen, Susan Y Green, Anna Xue, Vicente Orozco-Sevilla, Scott M Leikin, Marc R Moon, Subhasis Chatterjee

Faculty, Staff and Students Publications

Objective: Failure to rescue (FTR) is a metric of postoperative care, measuring a center's ability to prevent operative death after a surgical complication. We evaluated trends in and contributors to FTR after proximal aortic surgery at a high-volume institution.

Methods: Of 4180 patients in our single practice who underwent open proximal aortic repair from 1990 to 2024, 1304 (31.2%) had at least 1 of 4 FTR-related complications identified by the Society of Thoracic Surgeons (STS). Operative death was defined as death within 30 days of surgery or before hospital discharge or transfer. We analyzed FTR rate by specific complication, including …

Prospective Evaluation Of The European Society Of Cardiology 0/1h-Algorithm’S Safety And Efficacy For Triage Of Patients With Suspected Myocardial Infarction (Presc1se-Mi): Rationale And Design Of A Prospective International Multicenter Stepped-Wedge Cluster Randomized Controlled Trial, Jasper Boeddinghaus, Paolo Bima, Luca Crisanti, Dagmar I Keller, Ksenija Slankamenac, Michael Christ, Philipp Schuetz, Andrea Wiencierz, Ivo Strebel, Julia Reinhardt, Iryna Vyshnevska, Tzu-Ying Tsao, Felix Mahfoud, Maria Pia Ruggieri, Stephan Steuer, Òscar Miró, Veli-Pekka Harjola, Fulvio Morello, Peiman Nazerian, Dominik Roth, José Luis Zamorano, Deborah Erica Gannon, Jason Pott, Mohammed Oa Abubakr, Hyun Suk Yang, Joe Young, Richina Bicette, Andreea Cuculici, Héctor Bueno, Juan Sanchis, Christian Mueller

Faculty, Staff and Students Publications

Background: International practice guidelines recommend the more rapid European Society of Cardiology (ESC) 0/1h-algorithm for the triage of patients with suspected myocardial infarction (MI) as the preferred option and consider the ESC 0/3h-algorithm as an alternative. However, many centers worldwide have not yet adopted the ESC 0/1h-algorithm in clinical practice due to uncertainty which approach best balances safety and efficacy.

Methods: PRESC1SE-MI (PRospective Evaluation of the European Society of Cardiology 0/1h-algorithm`s Safety and Efficacy for Triage of Patients with Suspected Myocardial Infarction) is an international, investigator-initiated multicenter, stepped-wedge, cluster randomized controlled trial. At least 52,156 consecutive adult patients with nontraumatic …

Training In Medications For Opioid Use Disorder And Buprenorphine Prescribing In The Post X-Waiver Era: Insights From A Nationwide, Multispecialty Survey, Sung In H Kim-Vences, Justin Nguyen, Jacqueline M Hirth, Kyle P Suen, Colleen A Keough, Roger Zoorob, Alicia A Kowalchuk

Faculty, Staff and Students Publications

Objective: The January 2023 repeal of the X-waiver aimed to reduce regulatory barriers to buprenorphine prescribing and enhance patient access to medications for opioid use disorder (MOUD). Its impact on prescribing by non-addiction-trained physicians, the integration of MOUD training into residency programs, and the role of mandated training on clinical practice remain unclear.

Methods: A 2024 online survey assessed physicians' awareness of the X-waiver repeal, exposure to MOUD training, and changes in buprenorphine prescribing. Multivariable logistic regression evaluated the independent effect of MOUD training and whether mandatory versus voluntary formats influenced prescribing behavior.

Results: Among 959 physicians (42.7 % residents), …

Cyclic Amp-Dependent Regulation Of Ryanodine Receptors In Healthy And Diseased Hearts, Mohit M Hulsurkar, Isabelle Ong, Joshua A Keefe, Issam H Abu-Taha, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

Cyclic adenosine monophosphate (cAMP) is a critical second messenger in cardiomyocytes, regulating essential cellular functions. Upon G-protein-coupled receptor stimulation, adenylyl cyclase (AC) synthesizes cAMP, which phosphodiesterase (PDE) enzymes subsequently degrade. Recent studies challenge the traditional view of uniform cAMP signaling, revealing nanodomain-specific regulation within cardiomyocytes. This localized cAMP signaling modulates key Ca2+-handling proteins, including ryanodine receptor type-2 (RyR2), through channel-bound protein kinases and PDEs. Additionally, nucleoside-diphosphate kinases (NDPKs), particularly NDPK-C, contribute to cAMP synthesis and RyR2 regulation. Elevated NDPK-C levels in failing hearts correlate with increased cAMP levels, enhanced sarcoplasmic reticulum Ca2+ release, and cardiac arrhythmias. Furthermore, cAMP influences the …

Recognising Type 5 Diabetes – Authors’ Reply, Meredith Hawkins, Peter Schwarz, Chittaranjan S Yajnik, Mandeep Bajaj, Alvin C Powers, Michael S Boyne, Sarah Wild, Dirk L Christensen, Silver Bahendeka, Angus G Jones, Satinath Mukhopadhyay, Kaushik Ramaiya, David Phillips, Sylvia Kehlenbrink, Davis Kibirige, Charlotte Bavuma, Noel P Somasundaram, Debbie S Thompson, Jacko Abodo, Shitaye Alemu, Prasad Katulanda, Faruque Pathan, Shahjada Selim, Sarah Mathai, Mini Joseph, Mahindra Sonawane, Sandeep Mathur, Shajith Anoop, Sadishkumar Kamalanathan, Prosenjit Mondal, Dukhabandhu Naik, Ullas Kolthur-Seetharam, Riddhi Dasgupta, Felix Jebasingh, Nihal Thomas, Pradnyashree Wadivkar, Allan A Vaag

Faculty, Staff and Students Publications

No abstract provided.

Baseline Characteristics In The Synchronize™-2 Randomized Phase 3 Trial Of Survodutide, A Glucagon Receptor/Glp-1 Receptor Dual Agonist, For Obesity In People With Type 2 Diabetes, Sean Wharton, Carel W Le Roux, Biykem Bozkurt, Elke Platz, Gabriele Bleckert, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Isabel M Kloer, Lee M Kaplan

Faculty, Staff and Students Publications

Aims: Survodutide is an investigational glucagon receptor/glucagon-like peptide-1 receptor dual agonist that has shown promise for treating obesity and its complications in Phase 2 trials. Two double-blind, randomized, global Phase 3 trials are designed to assess the efficacy and safety of survodutide for treatment of obesity-SYNCHRONIZE™-1 in people with obesity without type 2 diabetes (T2D) and SYNCHRONIZE™-2 in people with obesity and T2D. This paper describes the baseline characteristics of participants in SYNCHRONIZE-2 (ClinicalTrials.gov identifier NCT06066528).

Materials and methods: Participants aged ≥18 years with a body mass index (BMI) ≥27 kg/m2 and T2D were randomized 1:1:1 to weekly subcutaneous …

Icosapent Ethyl Reduces Cvd Risk In Cardiovascular-Kidney-Metabolic Syndrome: Reduce-It Ckm, Michael Miller, Deepak L Bhatt, Eliot A Brinton, Terry A Jacobson, Ph Gabriel Steg, Steven B Ketchum, Armando Lira Pineda, Jean-Claude Tardif, Christie M Ballantyne

Faculty, Staff and Students Publications

Background/introduction: Cardiovascular-kidney-metabolic (CKM) syndrome was recently identified as a cardiometabolic disorder that incorporates chronic kidney disease with the metabolic syndrome (MetS). REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was an international, double-blind, placebo-controlled trial that randomized hypertriglyceridemic (TG, 150-499 mg/dL) statin-treated patients with established cardiovascular disease (CVD) or diabetes and multiple CVD risk factors to icosapent ethyl (IPE) or placebo (4 grams/day). It is unknown if renal insufficiency added to MetS confers incremental CVD risk in secondary prevention patients without diabetes and if IPE lowers that risk.

Methods: The current study evaluated the secondary prevention patient subgroup with …

The Reversibility Of Urate Tophi With Treat-To-Target In Gout: All Gone. Forever?, Jasvinder A Singh

Faculty, Staff and Students Publications

No abstract provided.

The Hidden Link Between Endometriosis And Obesity: A State-Of-The-Art Review, Shefali N Desai, Christina C Reed, Yamely Mendez, Qiannan Yang, Xiaoming Guan

Faculty, Staff and Students Publications

Endometriosis remains an under-researched disease with a wide range of symptoms. Endometriosis reduces a woman's quality of life and professional productivity, yet its exact causes, risk factors, and treatment have yet to be elucidated. Body mass index and endometriosis have been observed to be inversely related; however, this relationship may only be a correlation rather than a causation. Obesity may play a role in the inflammation and cell proliferation associated with endometriosis through the complex signaling pathways of adipokines. A literature review was done on endometriosis and obesity to gain insight and synthesize knowledge about opportunities to improve endometriosis care, …

Trans-Broad-Ligament Abdominal Cerclage Versus Blind Needle-Piercing Abdominal Cerclage During Pregnancy: A Comparison Of Surgical Outcomes, Qiannan Yang, Daniel Y Lovell, Joseph Nassif, Lubna Chohan, Jugnu Biba Nijjar, Nurul Farhanah Binte Abdul Latif, Zhenkun Guan, Xiaoming Guan

Faculty, Staff and Students Publications

No abstract provided.

Purpuric Pityriasis Rosea In A 7-Year-Old Girl: A Rare Variant With Generalized Involvement, Ying-Ying Qian, Ya-Fen Wu, Ting Zhang, Ji-Bing Li, Si-Yuan Song, Wei Li

Faculty, Staff and Students Publications

A 7-year-old girl presented with a 10-day history of generalized purpura and petechiae. The eruption began with a solitary violaceous macule on the trunk and progressed within 1 week to multiple oval and round dark-red to violaceous purpuric macules, ecchymoses, and petechiae affecting the face, trunk, and extremities. Lesions were distributed parallel to skin cleavage lines with a characteristic “Christmas-tree” pattern on the back (Fig 1). No oropharyngeal lesions were noted on examination, and the patient denied sore throat or oral discomfort. She reported no pruritus, pain, fever, or systemic symptoms.

Pair-Feeding Study Designs Can Create Biases And Inflate Type I Error Rates: A Simulation Study, Wasiuddin Najam, Daniel E Kpormegbey, Deependra K Thapa, Bret Rust, Lilian Golzarri-Arroyo, Lance H Baumgard, Louis Wai-Tong Fan, Joseph G Ibrahim, Edith J Mayorga, David B Allison

Children’s Nutrition Research Center Staff Publications

Objective: Pair-feeding is a study design element where one group's food intake is provided to another group to assess whether a treatment effect is independent of food intake. Investigators often assume equivalent food intake across experimental conditions and exclude it from the statistical analysis. However, the impact of this practice on type I error (T1Er) rates has not been quantified.

Methods: We conducted a Monte Carlo simulation in which animals were assigned baseline weights and food intakes, then randomized to non-pair-fed or pair-fed groups. Daily food intake for both groups was initially drawn from the baseline food intake distribution. For …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach, Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary A Churchill, David B Allison

Children’s Nutrition Research Center Staff Publications

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

Unravelling The Molecular Mechanisms Causal To Type 2 Diabetes Across Global Populations And Disease-Relevant Tissues, Ozvan Bocher, Ana Luiza Arruda, Satoshi Yoshiji, Chi Zhao, Alicia Huerta-Chagoya, Chen-Yang Su, Xianyong Yin, Davis Cammann, Henry J Taylor, Jingchun Chen, Ken Suzuki, Ravi Mandla, Ta-Yu Yang, Fumihiko Matsuda, Josep M Mercader, Jason Flannick, James B Meigs, Alexis C Wood, Marijana Vujkovic, Benjamin F Voight, Cassandra N Spracklen, Jerome I Rotter, Andrew P Morris, Eleftheria Zeggini

Children’s Nutrition Research Center Staff Publications

Type 2 diabetes (T2D) is a prevalent disease arising from complex molecular mechanisms. Here we leverage T2D genetic associations to identify causal molecular mechanisms in an ancestry-aware and tissue-aware manner. Using two-sample Mendelian randomization corroborated by colocalization across four global ancestries, we analyse 20,307 gene and 1,630 protein expression levels using blood-derived cis-quantitative trait loci (QTLs). We detect causal effects of genetically predicted levels of 335 genes and 46 proteins on T2D risk, with 16.4% and 50% replication in independent cohorts, respectively. Using gene expression cis-QTLs derived from seven T2D-relevant tissues, we identify causal links between the expression of 676 …

13 C-Spirulina Gastric Emptying Breath Test Normative Values In Healthy Children: A Multicenter Study With Comparison To Symptomatic Children, Katja Karrento, Bruno P Chumpitazi, Liyun Zhang, Pippa Simpson, Robert J Shulman

Faculty, Staff and Students Publications

Introduction: Diagnosing pediatric gastroparesis presents a significant challenge due to lack of normative data in children. We aimed to determine normative values for gastric emptying using the nonradioactive 13 C-Spirulina gastric emptying breath test ( 13 C-GEBT) in a large cohort of healthy children (HC) and examine differences compared to children with gastroparesis-like symptoms (GLS).

Methods: A total of 301 HC ages 7-18 years completed the 13 C-GEBT with 10 different breath samples × 4 hours. 13 CO 2 excretion rate (kPCD) was determined by change in 13 CO 2 / 12 CO 2 . Outcome variables included: kPCD at …

A Murine Model Of Cardiovascular-Kidney-Metabolic Syndrome Demonstrates Compromised Limb Function In The Ischemic Hind Limb, Saran Lotfollahzadeh, Herreet Paul, Joshua Bonifacio, Ricardo Almiron, Isaac Hockestra, Kylla Przekop, Trent Yamamoto, Maria Carmen Piqueras, Wenqing Yin, Kashvi Sethuraman, Asha Jose, Marina Malikova, Jeffrey J Siracuse, Mostafa Belghasem, Howard Cabral, Nazish Sayed, Vipul C Chitalia

Faculty and Staff Publications

Key Points:

1. Cardiovascular-kidney-metabolic (CKM) is a global public health problem; however, its mediators remain poorly known, in part due to the lack of a reliable animal model.

2. A combination of high fat and adenine diet recapitulate some of the CKD and metabolic phenotypes of CKM.

3. This model also demonstrates myocardial fibrosis and peripheral artery disease with sex-based differences and can be leveraged to probe mechanisms of CKM.

Background: Cardiovascular-kidney-metabolic (CKM) syndrome is a public health problem in the United States and results in premature cardiovascular disease at a relatively preserved GFR. The molecular mediators of CKM are poorly understood, partly …

Enteral And Intravenous Supplementation Of Arginine And Citrulline Fail To Prevent Necrotizing Enterocolitis In Preterm Neonatal Pigs, Caitlin Vonderohe, Julia Garcia Mancebo, Valeria Melendez Hebib, Barbara Stoll, Inka Didelija, Sarah Elefson, Mahmoud Mohammad, Brooklynn Earls, Greg Guthrie, Doug Burrin

Children’s Nutrition Research Center Staff Publications

Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants with a morality rate that approaches 50%. Arginine has been widely studied in the field of clinical nutrition as a supplement for patients experiencing critical illness because it can be metabolized into nitric oxide, an important agent for supporting immunity and microcirculation. Citrulline has received less attention but can be metabolized into arginine and has a much longer plasma half-life than arginine. We used the highly translational preterm pig model to determine the effect of intravenous and enteral supplementation of arginine and citrulline on NEC incidence in …

Fireproof: Intricacies Of Microglial Biology, Wei Cao

Faculty, Staff and Student Publications

No abstract provided.

Cardiometabolic Indicators Of Cognitive Impairment In The Cameron County Hispanic Cohort, Fadi I Musfee, Seema Agarwal, Vahed Maroufy, Chelsea Liu, Joseph B Mccormick, Susan Fisher-Hoch, Sean I Savitz

Faculty, Staff and Student Publications

Background

Objective

Methods

Multi-Trait And Multi-Ancestry Genetic Analysis Of Comorbid Lung Diseases And Traits Improves Genetic Discovery And Polygenic Risk Prediction, Yixuan He, Wenhan Lu, Yon Ho Jee, Mu-Yi Shih, Ying Wang, Kristin Tsuo, David C Qian, James A Diao, Hailiang Huang, Chirag J Patel, Jinyoung Byun, Bogdan Pasaniuc, Elizabeth G Atkinson, Christopher I Amos, Yen-Chen Anne Feng, Matthew Moll, Michael H Cho, Alicia R Martin

Faculty, Staff and Students Publications

While respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma share many risk factors, most studies investigate them in isolation and in predominantly European-ancestry populations. Here, we conducted the most powerful multi-trait and multi-ancestry genetic analysis of respiratory diseases and auxiliary traits to date, identifying 25 new loci associated with lung function in individuals of East Asian ancestry. Using these results, we developed PRSxtra (cross-trait and cross-ancestry), a multi-trait and multi-ancestry polygenic risk score (PRS) approach that leverages shared components of heritable risk via pleiotropic effects. PRSxtra significantly improved the prediction of asthma, COPD and lung cancer compared …

Tumour-Brain Crosstalk Restrains Cancer Immunity Via A Sensory-Sympathetic Axis, Haohan K Wei, Chuyue D Yu, Bo Hu, Xing Zeng, Hiroshi Ichise, Liang Li, Yu Wang, Ruiqi L Wang, Ronald N Germain, Rui B Chang, Chengcheng Jin

Faculty, Staff and Student Publications

Body–brain communication has emerged as a key regulator of tissue homeostasis1–5. Solid tumours are innervated by different branches of the peripheral nervous system and increased tumour innervation is associated with poor cancer outcomes6–8. However, it remains unclear how the brain senses and responds to tumours in peripheral organs, and how tumour–brain communication influences cancer immunity. Here we identify a tumour–brain axis that promotes oncogenesis by establishing an immune-suppressive tumour microenvironment. Combining genetically engineered mouse models with neural tracing, tissue imaging and single-cell transcriptomics, we demonstrate that lung adenocarcinoma induces innervation and functional …

Local Delivery Of Mir-27a* Using Ultrasound-Targeted Microbubble Cavitation Inhibits Squamous Cell Carcinoma Growth, Nikhil S Chari, Cheng Chen, Thiruganesh Ramasamy, Xucai Chen, Geetika Wadhwa, Anurag N Paranjape, Stephen Y Lai, Flordeliza S Villanueva

Faculty, Staff and Student Publications

Objective: Ultrasound-targeted microbubble (MB) cavitation (UTMC) is an image-guided therapeutic oligonucleotide delivery platform utilizing intravenously injected gas-filled ultrasound contrast agents, which carry the therapeutic on the MB shell. During transit of MBs in the microcirculation of target tissue, ultrasound causes MB oscillation, facilitating endocytosis-independent payload uptake within insonified cells. Here, we tested the hypothesis that UTMC-mediated miR-27a* delivery will reduce tumor growth rate and result in accumulation of miR-27a* within tumor cells and the tumor microenvironment.

Methods: We used UTMC to deliver miR-27a* to SCC-VII cells in vitro and in SCC-VII mouse tumor models. Pulsed ultrasound was delivered during intravenous …

A Comparative Study Of Statistical Methods For Identifying Differentially Expressed Genes In Spatial Transcriptomics, Yishan Wang, Chenxuan Zang, Ziyi Li, Charles C Guo, Dejian Lai, Peng Wei

Faculty, Staff and Student Publications

Spatial transcriptomics (ST) provides unprecedented insights into gene expression patterns while retaining spatial context, making it a valuable tool for understanding complex tissue architectures, such as those found in cancers. Seurat, by far the most popular tool for analyzing ST data, uses the Wilcoxon rank-sum test by default for differential expression analysis. However, as a nonparametric method that disregards spatial correlations, the Wilcoxon test can lead to inflated false positive rates and misleading findings. This limitation highlights the need for a more robust statistical approach that effectively incorporates spatial correlations. To this end, we propose a Generalized Estimating Equations (GEE) …

Circulating Metabolites, Genetics And Lifestyle Factors In Relation To Future Risk Of Type 2 Diabetes, Jun Li, Jie Hu, Huan Yun, Zhendong Mei, Xingyan Wang, Kai Luo, Marta Guasch-Ferré, Xikun Han, Buu Truong, Jordi Merino, Chengyong Jia, Miguel Ruiz-Canela, Casey M Rebholz, Eun Hye Moon, Taryn Alkis, Guning Liu, Jie Yao, Xiyuan Zhang, Bianca C Porneala, Jordi Salas-Salvadó, Thomas J Wang, Josée Dupuis, Elizabeth Selvin, Xiuqing Guo, Shilpa N Bhupathiraju, Jennifer A Brody, Yongmei Liu, Alexis C Wood, Kari E North, Su Yon Jung, Ching-Ti Liu, Nona Sotoodehnia, Simin Liu, Lesley F Tinker, A Heather Eliassen, Joann E Manson, Jose C Florez, Robert E Gerszten, Clary B Clish, Liming Liang, Rozenn N Lemaitre, Katherine L Tucker, Stephen S Rich, Jerome I Rotter, Miguel Angel Martínez-González, Kathryn M Rexrode, James B Meigs, Eric Boerwinkle, Robert C Kaplan, Frank B Hu, Bing Yu, Qibin Qi

Faculty, Staff and Student Publications

The human metabolome reflects complex metabolic states affected by genetic and environmental factors. However, metabolites associated with type 2 diabetes (T2D) risk and their determinants remain insufficiently characterized. Here we integrated blood metabolomic, genomic and lifestyle data from up to 23,634 initially T2D-free participants from ten cohorts. Of 469 metabolites examined, 235 were associated with incident T2D during up to 26 years of follow-up, including 67 associations not previously reported across bile acid, lipid, carnitine, urea cycle and arginine/proline, glycine and histidine pathways. Further genetic analyses linked these metabolites to signaling pathways and clinical traits central to T2D pathophysiology, including …

Neurological Recovery After Ich Is Mediated By The Aryl Hydrocarbon Receptor-Bilirubin Interplay Through Improved Erythrophagocytosis, Xiurong Zhao, Shun-Ming Ting, Guanghua Sun, Jaroslaw Aronowski

Faculty, Staff and Student Publications

Hematoma clearance after ICH is a pro-hemostatic process aiming at repair/recovery and is achieved through microglia/macrophages (MMΦ)-mediated erythrophagocytosis. Upon the engulfment of masses of erythrocytes and toxic hemolysis products, hemoglobin and heme, phagocytes convert them to bilirubin (BrB). Bilirubin is essentially not soluble in water and when overproduced, it precipitates within the cell causing injury. Thus, keeping bilirubin soluble and at a low intracellular level is needed for proper function of MMΦ. Here, using cultured microglia (MG), we found that intracellular formation of BrB in microglia during erythrophagocytosis coincides with the activation of transcription factor AhR, and AhR target genes …

Partial Laryngectomy For Thyroid Cancer: A Single Institution Case Series With Operative Techniques, Ella E Hawes, Victoria E Banuchi, Anastasios Maniakas, Jennifer R Wang, Paul H Graham, Julia D Diersing, Naifa L Busaidy, Maria E Cabanillas, Ramona Dadu, Sarah Hamidi, Priyanka Iyer, Steven G Waguespack, Salmaan Ahmed, Sahar Alizada, Alexandra Belcastro, Ranim Alsharif, Mimi I Hu, Mark E Zafereo

Faculty, Staff and Student Publications

Background: Partial laryngectomy has been well described as a management option for T1-3 laryngeal squamous cell cancers. However, there are a few case reports of partial laryngeal surgery for locally advanced thyroid carcinoma.

Methods: This is a case series of five patients with thyroid carcinoma (one primary and four recurrent) with laryngeal involvement who underwent partial laryngectomy.

Results: All patients had complete surgical resection without perioperative complications or postoperative speech or swallowing deficits, and none required a feeding tube or tracheostomy tube. No patients had postoperative radiation therapy or started systemic therapy within 2 years of surgery, while two patients …

Circulating Fatty Acid Binding Protein 4 (Fabp-4) Concentrations And Mortality In Individuals With Colorectal Cancer In The European Prospective Investigation Into Cancer And Nutrition Study, Thu Thi Pham, Katharina Nimptsch, Krasimira Aleksandrova, Mazda Jenab, Veronika Fedirko, Anja Olsen, Anne Tjønneland, Claire Cadeau, Gianluca Severi, Matthias B Schulze, Renée Turzanski Fortner, Verena Katzke, Claudia Agnoli, Carlotta Sacerdote, Rosario Tumino, Simona Signoriello, Camino Trobajo-Sanmartín, Jesús-Humberto Gómez, María-Dolores Chirlaque, Maria-Jose Sánchez, Marta Crous-Bou, Anne May, Alicia Heath, Dagfinn Aune, Elisabete Weiderpass, Tobias Pischon

Faculty, Staff and Student Publications

Human fatty acid binding protein‐4 (FABP‐4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity–mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC‐specific, non‐CRC‐specific, and all‐cause mortality by FABP‐4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC …

Introducing A New Frontier In The Journal Of Pediatric Rehabilitation Medicine: An Interdisciplinary Approach Throughout The Lifespan: The Pediatric Brain Injury Section, Michael Green, Glendaliz Bosques, Kimberly Davis, Brenda Eagan-Johnson, Carty Husted

Faculty, Staff and Student Publications

No abstract provided.