Medical Specialties Commons^™

Cardiac Rhythm Devices In Heart Failure With Reduced Ejection Fraction – Role, Timing, And Optimal Use In Contemporary Practice European Journal Of Heart Failure Expert Consensus Document, Biykem Bozkurt, Wilfried Mullens, Christophe Leclercq, Andrea M Russo, Gianluigi Savarese, Michael Böhm, Loreena Hill, Koichiro Kinugawa, Naoki Sato, William T Abraham, Antoni Bayes-Genis, Alexandre Mebazaa, Giuseppe M C Rosano, Shelley Zieroth, Cecilia Linde, Javed Butler

Faculty, Staff and Students Publications

Guidelines for management of heart failure with reduced ejection fraction (HFrEF) emphasize personalized care, patient engagement, and shared decision-making. Medications and cardiac rhythm management (CRM) devices are recommended with a high level of evidence. However, there are significant disparities: patients who could benefit from devices are frequently referred too late or not at all. Misconceptions about device therapy and the notion that the needs of patients (especially the prevention of sudden cardiac death) can now be met by expanding drug therapies may play a role in these disparities. This state-of-the-art review is produced by members of the DIRECT HF initiative, …

Baseline Cognition And Demographic, Lifestyle, And Cardiovascular Risk Factors In Us Pointer, Kathryn V Papp, Sarah Tomaszewski Farias, Marjorie Howard, Amber Thro, Tiia Ngandu, Brad Caudle, Bonnie C Sachs, Michelle Chan, Kristin R Krueger, Elizabeth R T Hartman, Athene Lee, Michele K York, Marie T Austin, Kathryn E Demos, Thomas M Holland, Xiaoyan Leng, Rema Raman, Heather M Snyder, Maria C Carrillo, Rachel A Whitmer, Mark A Espeland, Laura D Baker

Faculty, Staff and Students Publications

Introduction: Validation of the primary cognitive composite and baseline cognitive characteristics are presented for the US-Study-to-Protect-Brain-Health-Through-Lifestyle-Intervention-to-Reduce-Risk (US POINTER).

Methods: US POINTER is a multicenter, randomized clinical trial of two lifestyle interventions testing cognitive benefit in older adults without significant cognitive impairment but at-risk for decline due to well-established factors. Cognition is measured using a global cognitive composite (US POINTER modified Neuropsychological Test Battery-PmNTB).

Results: The PmNTB is a valid cognitive composite, exhibiting good psychometric properties and tracking with other established outcomes. Among the 2111 enrolled participants (mean age = 68.2 years, 69% women, 31% from race and ethnic minoritized groups), …

Diagnostic Accuracy Of Screening Tools For Depression And Anxiety In Cervical Dystonia, Davide Martino, Mehrafarin Ramezani, Steven Bellows, Brian D Berman, Florence Ching-Fen Chang, Jeanne Feuerstein, Victor Fung, Gamze Kilic Berkmen, Irene A Malaty, Claire Maciver, Scott A Norris, Kathryn J Peall, Joel S Perlmutter, Sarah Pirio Richardson, Laura J Wright, Zahra Goodarzi, Hyder A Jinnah

Faculty, Staff and Students Publications

Introduction: Despite their high prevalence and impact, depression and anxiety are not routinely screened for, and accuracy of screening procedures is unknown in adult-onset dystonia. We evaluated accuracy parameters of selected self-rated scales for depression and anxiety in patients with idiopathic cervical dystonia (CD).

Methods: Two-hundred-and-ten patients with idiopathic CD were recruited from 10 movement disorders centers from the US, Canada, Australia, and UK. At the end of each botulinum toxin cycle, participants were administered the Adult Standard Mini-International Neuropsychiatric Interview (MINI) as reference standard for depression and anxiety. Participants completed 8 self-administered index instruments (2 for depression, 2 for …

Formation Of An Expanding Memory Representation In The Hippocampus, Sachin P Vaidya, Guanchun Li, Raymond A Chitwood, Yiding Li, Jeffrey C Magee

Faculty, Staff and Students Publications

How brain networks connected by labile synapses store new information without catastrophically overwriting previous memories remains poorly understood. To examine this, we tracked the same population of hippocampal CA1 place cells (PCs) as mice learned a task for 7 days. We found evidence of memory formation as both the number of PCs maintaining a stable place field and the stability of individual PCs progressively increased across the week until most of the representation was composed of long-term stable PCs. The stable PCs disproportionately represented task-related learned information, were retrieved earlier within a behavioral session and showed a strong correlation with …

Immediate Skin-To-Skin Contact And Postpartum Hemorrhagic Morbidity, Rachel L Wiley, Ipsita Ghose, Dana R Canfield, Minhazur R Sarker, Hector Mendez-Figueroa, Suneet Chauhan

Faculty, Staff and Students Publications

Objective: To examine rates of postpartum hemorrhagic (PPH) morbidity among patients who did and did not have immediate skin-to-skin contact (SSC).

Methods: This study was a retrospective cohort of all non-anomalous, term singleton vaginal births at a Level IV center over 2 years. Exclusion criteria included COVID-19. Immediate SSC was defined as at least 60 min of direct contact initiated between parturient and neonate within 10 min of birth. The primary outcome was a composite of maternal morbidity related to PPH compared among those with and without immediate SSC. We used multivariable Poisson regression adjusted for possible confounders with robust …

Role Of Kctd13 In Modulating Ar And Sox9 Expression In Different Penile Cell Populations, Carolina J Jorgez, Ahmed Chahdi, Hunter Flores, Marisol O'Neill, Abhishek Seth

Faculty, Staff and Students Publications

Objective: Micropenis is a condition with significant physical and psychological implications caused mainly by decreased androgen action in penile development. Kctd13-knockout (Kctd13-KO) mice have micropenis, cryptorchidism, and fertility defects because of reduced levels of androgen receptor (AR) and SOX9. We hypothesized that normalizing the levels of AR and SOX9 in the Kctd13-KO penis could help us to understand the mechanism of action of these signaling pathways on penile development.

Methods: We generated transgenic mice lacking Kctd13 and conditionally expressing AR in the urethral mesenchyme after Cre activation with Twist2cre (Kctd13-KO; AR-CMV; Twist2cre; herein called AR+), and Sox9 in the urethral …

The Somatic Mosaicism Across Human Tissues Network, Tim H H Coorens, Ji Won Oh, Yujin Angelina Choi, Nam Seop Lim, Boxun Zhao, Adam Voshall, Alexej Abyzov, Lucinda Antonacci-Fulton, Samuel Aparicio, Kristin G Ardlie, Thomas J Bell, James T Bennett, Bradley E Bernstein, Thomas G Blanchard, Alan P Boyle, Jason D Buenrostro, Kathleen H Burns, Fei Chen, Rui Chen, Sangita Choudhury, Harsha V Doddapaneni, Evan E Eichler, Gilad D Evrony, Melissa A Faith, Thomas G Fazzio, Robert S Fulton, Manuel Garber, Nils Gehlenborg, Soren Germer, Gad Getz, Richard A Gibbs, Raquel G Hernandez, Fulai Jin, Jan O Korbel, Dan A Landau, Heather A Lawson, Niall J Lennon, Heng Li, Yan Li, Po-Ru Loh, Gabor Marth, Michael J Mcconnell, Ryan E Mills, Stephen B Montgomery, Pradeep Natarajan, Peter J Park, Rahul Satija, Fritz J Sedlazeck, Diane D Shao, Hui Shen, Andrew B Stergachis, Hunter R Underhill, Alexander E Urban, Melissa W Vondran, Christopher A Walsh, Ting Wang, Tao P Wu, Chenghang Zong, Eunjung Alice Lee, Flora M Vaccarino

Center on Aging Staff Publications

From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues …

Mass Spectrometry Imaging Reveals Alterations In Protein And N-Glycan Molecular Signatures In Endometriosis Tissues, Monica Lin, Erin H Seeley, Suzanne Ledet, Christina Salazar, Michael T Breen, Livia S Eberlin

Faculty, Staff and Students Publications

Endometriosis is a gynecological condition characterized by the uncontrolled growth of endometrial-like tissue outside the uterine cavity. Although highly prevalent, the biological mechanisms of endometriosis are poorly understood, and the disease is often misdiagnosed due to the unavailability of pre-operative diagnostic methods. Thus, better characterization of molecular markers of endometriosis are critical to improve our understanding of the disease and management of patients. Here, we used matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) imaging to investigate protein and N-glycan molecular signatures in eutopic endometrium and endometriosis lesions from tissues prospectively collected from patients. MALDI MS imaging of intact proteins …

A Phase 2 Trial Of Short-Term Intravenous N-Acetylcysteine In Biliary Atresia After Kasai Portoenterostomy, Sanjiv Harpavat, Kristin A Borovsky, Michael E Scheurer, Laurel Cavallo, Franca E Erhiawarie, Sanjeev Vasudevan, Adam M Vogel, Dana Cerminara, Elizabeth M Tessier, Kalyani R Patel, Sridevi Devaraj, Benjamin L Shneider

Center for Medical Ethics and Health Policy Staff Publications

Background: For infants with biliary atresia, the only treatment that can establish bile flow and delay need for liver transplant is the Kasai portoenterostomy (KP). Unfortunately, the KP has variable success. In this study, we hypothesized that intravenous N-acetylcysteine (IV NAC) treatment following KP would improve bile flow.

Methods: This was a phase 2 study following the two-stage "minimax" trial design. Participants received IV NAC (150 mg/kg/day) for 7 days after KP, and the primary endpoint was achieving total serum bile acids (TSBA) ≤10 μmol/L within 24 weeks of KP. Secondary endpoints were clinical markers and the occurrence of sentinel …

Dessicating Stress Triggers And Exacerbates Experimental Ocular Graft-Versus-Host-Disease, Uta Gehlsen, Martina Maass, Daniela Stary, Svenja Wagener-Ryczek, Gwen Musial, Manolis Pasparakis, Cintia S De Paiva, Michael E Stern, Philipp Steven

Faculty, Staff and Students Publications

Introduction: Chronic ocular graft-versus-host disease (oGVHD) is one of the most common complications after allogeneic hematopoietic stem cell transplantation (aHSCT). Recent studies indicate that desiccating stress by air-conditioning in transplantation wards increases the incidence of oGVHD. To test the hypothesis that experimental desiccating stress is a risk factor for oGVHD a mouse model of oGVHD was subjected to experimental desiccating stress.

Materials/methods: A previously established chemo-induced minor-mismatch mouse model of oGVHD was used. One group was challenged with desiccating stress for 18 days and compared to non-desiccated GVHD animals. Clinical phenotyping was performed weekly and ocular tissue and regional lymph …

High Prevalence Of Strongyloides Stercoralis In People Living With Hiv: A Critical Health Challenge In The Peruvian Amazon Basin, Silvia Otero-Rodriguez, Martin Casapia-Morales, Viviana Pinedo-Cancino, Seyer Mego-Campos, Victoria-Ysabel Villacorta-Pezo, Jorge Parráguez-De-La-Cruz, Eva H Clark, Esperanza Merino, Jose-Manuel Ramos-Rincon

Faculty, Staff and Students Publications

Introduction: Strongyloidiasis is an important but underdiagnosed soil-transmitted helminthiasis, particularly in tropical areas and some vulnerable groups.

Objectives: To assess the parasitological prevalence, seroprevalence and sociodemographic factors of Strongyloides stercoralis infection in patients living with human immunodeficiency virus (PLWH) in an endemic area.

Materials and methods: We performed a cross-sectional study of strongyloidiasis in 537 PLWH in two hospitals in Iquitos, Peru, from 20 Oct 2023 to 20 May 2024. We tested patient sera using Strongyloides IgG enzyme-linked immunosorbent assay (ELISA) and stool via the modified Baermann technique and/or charcoal fecal culture as highly sensitive parasitological techniques. We used multivariable …

Clinically Validated Graphical Approaches Identify Hepatosplenic Multimorbidity In Individuals At Risk Of Schistosomiasis, Yin-Cong Zhi, Simon Mpooya, Narcis Kabatereine, Betty Nabatte, Christopher Opio, Narcis Kabatereine, Goylette Chami

Internal Medicine, East Africa

The global burden of multimorbidity is increasing yet poorly understood, owing to insufficient methods for modelling complex systems of conditions. In particular, hepatosplenic multimorbidity has been inadequately investigated. From 17 January to 16 February 2023, we examined 3186 individuals aged 5–92 years from 52 villages across Uganda within the SchistoTrack Cohort. Point-of-care B-mode ultrasound was used to assess 45 hepatosplenic conditions within the context of schistosomiasis (Schistosoma mansoni). Three graph learning methods for representing hepatosplenic multimorbidity were compared. Thresholds for including graph edges were found using graph kernels and tested with graph neural networks to assess predictive utility for unobserved …

The Pediatric Experience Collaborative: Paving The Way In Pediatric Experience., Lauren Hamilton, Trenton House, Taylor B. Sewell, Harris Baden, Brianna Combs, Sara L. Toomey, Shehzad Saeed, Jana Rojas, Molly Warneke, Maureen Hoff, Andréa Aken'ova, Lisa Rubino, Dana Ileana Williams, Samuel P. Hanke

Manuscripts, Articles, Book Chapters and Other Papers

Positive patient experience is associated with improved patient outcomes, but efforts to improve patient experience are often underprioritized, especially with respect to pediatric care. To address this challenge, leaders at several US children's hospitals established the Pediatric Experience Collaborative (PEC) in 2016 to leverage their collaboration and scale to optimize patient, family, and provider experiences. Since then, the PEC has steadfastly incorporated the patient and family perspective in all its endeavors (e.g., installing a family member as one of the organization's co-chairs); has created both structured opportunities and unstructured opportunities for learning and connection; and has embarked on multi-institutional research …

Anxiety And Depression In Today's Youth: A Current Look Into Assessment And Treatment., Meredith J. Scafe, Meghan Kanya, Meaghan Flynn, Ram Chettiar

Manuscripts, Articles, Book Chapters and Other Papers

Following the COVID-19 pandemic, the American Academy of Pediatrics (AAP), the American Academy of Child and Adolescent Psychiatry, and the Children's Hospital Association declared a national emergency in child and adolescent mental health. Rates of anxiety and depression in youth continue at unprecedented levels, contributing to rising numbers of suicide attempts and lowered school attendance. Though many medical providers are trained to assess and provide recommendations for anxiety and depression, many report feeling ill-equipped to address these concerns in a timely, feasible, and effective manner. We review the existing literature on screening for anxiety and depression in the medical setting …

Two Spectroscopy Devices Can Approximate Fruit And Vegetable Intake In A Racially And Ethnically Diverse Sample, Stephanie B Jilcott Pitts, Qiang Wu, Melissa N Laska, Nancy E Moran

Children’s Nutrition Research Center Staff Publications

Background: Assessing fruit and vegetable intake is important to determine the effectiveness of nutrition intervention studies. Few objective measures of fruit and vegetable intake have been directly compared within the same study participants.

Objectives: This study aims to compare the relative validity of 2 different skin spectrophotometry devices to serve as biomarkers of plasma carotenoid concentrations, self-reported fruit and vegetable intake (FVI), and carotenoid intake, to examine if both devices can be used to approximate FVI.

Methods: Human skin carotenoid scores (SCS, Veggie Meter-assessed) and color space measurement data from 2 prior studies were used. Participants' skin color space parameters …

A Brief Guide To Statistical Analysis Of Grouped Data In Preclinical Research, Colby J Vorland, Lilian Golzarri-Arroyo, David B Allison

Children’s Nutrition Research Center Staff Publications

Clustering and nesting (C&N) arise in many preclinical studies such as when animals are group-housed, share litters, or in cell culture. Ignoring C&N undermines the validity of analyses. We explain how C&N arise and valid designs and analyses.

Defining Lipedema’S Molecular Hallmarks By Multi-Omics Approach For Disease Prediction In Women, Leon G Straub, Jan-Bernd Funcke, Nolwenn Joffin, Chanmin Joung, Sara Al-Ghadban, Shangang Zhao, Qingzhang Zhu, Ilja L Kruglikov, Yi Zhu, Paul R Langlais, Ruth Gordillo, Karen L Herbst, Philipp E Scherer

Children’s Nutrition Research Center Staff Publications

Lipedema is a chronic disease in females characterized by pathologic subcutaneous adipose tissue expansion and hitherto remains without druggable targets. In this observational study, we investigated the molecular hallmarks of lipedema using an unbiased multi-omics approach. We found adipokine dysregulation in lipedema patients participating in a cross-sectional clinical study (ClinicalTrial.gov, NCT02838277), pointing towards the adipocyte as a key player. Analyses of newly generated transcriptomic (SRA, PRJNA940039) and proteomic (ProteomeXchange, PXD058489) datasets of early- and late-stage lipedema samples revealed a local downregulation of factors involved in inflammation. Concomitantly, factors involved in cellular respiration, oxidative phosphorylation, as well as in mitochondrial …

Reduction Of Neuronal Activity Mediated By Blood-Vessel Regression In The Adult Brain, Xiaofei Gao, Xing-Jun Chen, Meng Ye, Jun-Liszt Li, Nannan Lu, Di Yao, Bo Ci, Fei Chen, Lijun Zheng, Yating Yi, Shiwen Zhang, Zhanying Bi, Xinwei Gao, Yuanlei Yue, Tingbo Li, Jiafu Lin, Ying-Chao Shi, Kaibin Shi, Nicholas E Propson, Yubin Huang, Katherine Poinsatte, Zhaohuan Zhang, Dale B Bosco, Shi-Bing Yang, Ralf H Adams, Volkhard Lindner, Fen Huang, Long-Jun Wu, Hui Zheng, Simon Hippenmeyer, Ann M Stowe, Bo Peng, Marta Margeta, Qingchun Guo, Xiaoqun Wang, Qiang Liu, Jakob Körbelin, Martin Trepel, Hui Lu, Guoen Cai, Bo O Zhou, Bo Shen, Ying-Mei Lu, Wenzhi Sun, Jie-Min Jia, Feng Han, Hu Zhao, Robert M Bachoo, Woo-Ping Ge

Center on Aging Staff Publications

The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and …

Functional Regulation Of Macrophages By Ces1d-Mediated Lipid Signaling In Immunometabolism, Long J Shao, Fathima Elizondo, Feng Gao, Rabie Habib, Xin Li, Katherine Pham, Jazmin Ysaguirre, Maryam Elizondo, Shirindokht Shirazi, Kristin L Eckel-Mahan, Sean Hartig, Huaizhu Wu, Kai Sun

Faculty, Staff and Student Publications

Objective: Macrophage accumulation in metabolically active tissues during obesity is common in both animals and humans, but the lipid signaling mechanisms that trigger macrophage inflammation remain unclear. This study investigates the role of Ces1d, an unconventional lipase, in regulating macrophage inflammation under nutritional stress.

Methods: A myeloid-specific Ces1d knockout (LysM-Cre-Ces1d floxed/floxed, KO) mouse model was used for the studies. For in vitro tests, bone marrow-derived macrophages (BMDMs) from control (Ces1d floxed/floxed, WT) and KO mice were assessed for migration, polarization, and activation. For in vivo experiments, WT and KO mice were induced to obesity via a high-fat diet (HFD) and …

The Diabetes Prevention Program And Its Outcomes Study: Niddk's Journey Into The Prevention Of Type 2 Diabetes And Its Public Health Impact, Jill P Crandall, Dana Dabelea, William C Knowler, David M Nathan, Marinella Temprosa, Dpp Research Group

Children’s Nutrition Research Center Staff Publications

The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) presciently proposed the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin in comparison with placebo would reduce the development of diabetes in a high-risk population with prediabetes. After mean 2.8 years, ILS …

Metabolic Clearance Rate Of Insulin Across The Glucose Tolerance Spectrum By Race And Ethnicity In Youth With Obesity, Wonhee Cho, Fida Bacha, Hala Tfayli, Sojung Lee, Sara F Michaliszyn, Joon Young Kim, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Objective: Despite β-cell failure in youth with dysglycemia (i.e., impaired glucose tolerance [IGT] and type 2 diabetes), fasting insulin (FI) concentrations are elevated. Herein, we examined the following: 1) metabolic clearance rate of insulin (MCRI) in youth with obesity and normal glucose tolerance (NGT) versus those with IGT versus those with type 2 diabetes; 2) racial and ethnic differences in insulin dynamics; and 3) metabolic/adiposity correlates of MCRI.

Methods: A total of 206 youth underwent assessment of fasting glucose, FI, MCRI and peripheral insulin sensitivity (PIS), first-phase insulin secretion, disposition index, body composition, and abdominal adiposity.

Results: In type 2 …

To Pause With A Cliffhanger Or A Temporary Closure? The Differential Impact Of Serial Versus Episodic Narratives On Children's Physical Activity Behaviors, Amy Shirong Lu, Melanie C Green, Caio Victor Sousa, Jungyun Hwang, I-Min Lee, Debbe Thompson, Tom Baranowski

Children’s Nutrition Research Center Staff Publications

Research has supported the effectiveness of narratives for promoting health behavior, but different narrative presentation formats (serial vs. episodic) have seldom been compared. Suspense theories suggest that serial narratives, which do not provide a full resolution at the end of an episode, may create higher motivation for continued engagement with a story. Forty-four 8 to 12-year-old children were randomly assigned to watch an animation series designed for an existing active video game in which the plot was delivered either continuously across multiple episodes (serial) or in multiple yet relatively independent self-contained episodes (episodic). Controlling for social desirability, children who watched …

Inhibition Of Srebp-1c Rescues Hepatic Cyp7b1 Expression And Bile Acid Synthesis In Malnourished Mice, Xiaoyang Wan, Krishnakant G Soni, Jong Min Choi, Sun Yun Jung, Margaret E Conner, Geoffrey A Preidis

Faculty, Staff and Students Publications

Malnutrition decreases intestinal bile acids, resulting in inefficient nutrient absorption and impaired catch-up growth. Mechanisms by which bile acid depletion occurs in malnutrition are unknown. Using a mouse model of early-life malnutrition, we explored bile acid homeostasis, focusing on transcriptional repression of CYP7B1, a rate-limiting enzyme in the alternative pathway of bile acid biosynthesis, by SREBP-1c, a master regulator of lipid metabolism. Mice were maintained on a low-protein low-fat or isocaloric control chow until eight weeks of age when livers were harvested for proteome profiling, western blot, RT-qPCR, and chromatin immunoprecipitation. Cultured hepatocytes and mice were treated with the SREBP-1c …

Bibliometric Analysis Of Congenital Toxoplasmosis: A Ten-Year (2013-2023) Review Of Research Publications, Festus Mulakoli, Horatius Musembi, Ann Kimani

School of Nursing & Midwifery, East Africa

Background:Toxoplasma gondii, an obligate intracellular protozoan, infects more than one-third of the global population and causes toxoplasmosis, which can lead to severe fetal complications in pregnant women. The global prevalence of latent toxoplasmosis in pregnant women is 33.8%, with regional variations and risk factors, including the consumption of undercooked meat, exposure to cat feces, and consumption of contaminated water. Pregnant women lack sufficient awareness of these risk factors, necessitating enhanced education, regular screening, and counseling during antenatal care for early detection and management.

Aim: This study performed a comprehensive bibliometric analysis of research on congenital toxoplasmosis published between 2013 …

First-In-Human Phase 1 Study Of Khk2455 Monotherapy And In Combination With Mogamulizumab In Patients With Advanced Solid Tumors, Timothy A Yap, Olivier Rixe, Capucine Baldini, Ursa Brown-Glaberman, Sergey Efuni, David S Hong, Christophe Massard, Jameel Muzaffar, Andreea Varga, Emrullah Yilmaz, Yuta Ikawa, Lisa H Shiue, Yi Liu, Matthew W Hruska, Henry Zhao, Akihiro Tokunaga, Solmaz Sahebjam

Faculty, Staff and Student Publications

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that degrades tryptophan (Trp) to kynurenine (Kyn), which suppresses effector T cells and reduces antitumor activity. KHK2455 is a long-acting selective IDO1 inhibitor that blocks the heme component of the IDO holoenzyme. Mogamulizumab is a humanized immunoglobulin G1 monoclonal antibody targeting CCR4. KHK2455 + mogamulizumab demonstrated enhanced antitumor activity in preclinical studies, which led to a first-in-human, two-part, multicenter, open-label, phase 1, dose-escalation, cohort-expansion trial (ClinicalTrials.gov identifier NCT02867007) evaluating the safety/tolerability, pharmacokinetics, and IDO1 activity of KHK2455 alone and in combination with mogamulizumab in patients with treatment-refractory advanced solid tumors. …

Proceedings Of The 2025 Nassi Annual Meeting, Patrick C. Hsieh, Chiung-Chyi Shen, Alan S. Hilibrand, D. Scott Kreine, David R. O’Brien Jr., Hani H. Mhaidli, Jau-Ching Wu, Wen-Cheng Huang

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

The Loss Of Opa1 Accelerates Intervertebral Disc Degeneration And Osteoarthritis In Aged Mice, Vedavathi Madhu, Miriam Hernandaz-Meadows, Ashley Coleman, Kimheak Sao, Kameron Inguito, Owen Haslam, Paige Boneski, Hiromi Sesaki, Ruteja Barve, John Collins, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Recent studies have highlighted the importance of mitochondria in NP cells and articular chondrocyte health. Since the understanding of mechanisms governing mitochondrial dynamics in these tissues is lacking, we investigated the role of OPA1, a mitochondrial fusion protein, in their homeostasis. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and loss resulted in the dysregulation of autophagy. Metabolic profiling and

Validation Of Established Thyroid Ultrasound Volume Norms In A Chernobyl Cohort, Lydia B. Zablotska, Robert J. Mcconnell, Aleksandr V. Rozhko, Patrick O'Kane, Vasilina Yauseyenka, Mark P. Little, Victor Minenko, Vladimir Drozdovitch, Tamara Moskvicheva, Maureen Hatch, Tamara Yeudachkova, Kiyohiko Mabuchi, Elizabeth K. Cahoon

Department of Radiology Faculty Papers

OBJECTIVE: To establish thyroid ultrasound volume norms appropriate for studies of diffuse goiter in a cohort of children and adolescents from an iodine-deficient population exposed to 131I by the Chernobyl fallout.

METHODS: A cohort of 11,970 Belarusians aged ≤18 years at the time of the 1986 Chernobyl accident with individual thyroid radiation dose estimates was screened 10-18 years later. From these, a low-dose subset of 2,392 with no thyroid diseases was selected to construct age- and sex-specific normative values for thyroid ultrasound volume, compared to Belarusian Ministry of Health (MOH) norms and existing WHO and European standards.

RESULTS: Cohort-specific values …

Clinico-Epidemiological Characteristics Of Cerebral Venous Sinus Thrombosis In Kenya: A Retrospective Case Series, Taby Siika, Jaskirat Sokhi, Juzar Hooker, Sheila Waa, Anne Mwirigi, Jasmit Shah, Dilraj Sokhi

Internal Medicine, East Africa

Background: Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke that is more common in young, especially female, adults and can be challenging to diagnose due to its frequently non-specific presentation and diverse risk factors. Most cases are idiopathic, and international guidelines do not recommend routine investigations for underlying thrombophilia. Timely diagnosis, with prompt neuroimaging and guideline-based treatment, leads to good outcomes. However, in the literature on CVST from sub-Saharan Africa, the gap is substantial, with the few cases described as being related to systemic and/or brain infections. We describe here the largest cohort of CVST from the …

Higher Plasma Afb1 Concentration Is Associated With Increased Risk Of Hpv 16 And Hpv 18 Detection And Persistence Among Ugandan Women, Yan Tong, Miriam Nakalembe, Collins Mpamani, Carolyn Nakisige, Jane Namugga, Grace Banturaki, Philiph Tonui, Elkanah Orang'o

Obstetrics and Gynaecology, East Africa

Introduction: Aflatoxins are environmental hazards; potent carcinogenic and immunosuppressive agents that contaminates corn and other crops. A high proportion of hepatocellular carcinoma cases are caused by exposure to dietary aflatoxins. Cervical cancer is common among Ugandan women; this malignancy is caused by persistent infection with oncogenic HPV types. An analysis was performed to examine associations between plasma aflatoxin B1 (AFB1) detection and oncogenic HPV detection (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) and persistence among Ugandan women.

Methods: Ugandan women were enrolled in a prospective cohort study. Annual cervical swabs …