Digital Commons Network^™

Spinoplastic Surgery: A Review Of Techniques, Indications, And Optimal Patient Selection, Daniel Vernik, Camryn Payne, Krishna Sinha, Casey Martinez, Walter Nicholas Jungbauer, Jonathan L Jeger, Michael Bohl, Alexander E Ropper, Sebastian Winocour, Edward Reece

Faculty, Staff and Students Publications

Background/Objectives: Spinoplastic surgery is an emerging multidisciplinary field developed to address and reduce the complication of pseudoarthrosis following complex spinal reconstructions. While the number of spinal fusion procedures continues to rise every year, fusion failure rates remain as high as 40%. Although pseudoarthrosis may not always manifest clinically, it remains a leading cause of persistent pain and need for subsequent revision surgeries. The multidisciplinary collaboration between spine and plastic surgeons in spinoplastic surgery has therefore emerged as a proactive strategy aimed at preventing complications, particularly in patients identified as high-risk for pseudoarthrosis. As the patient population expands and spinoplastic surgery …

Phase Ii Basket Trial Of Dual Anti-Ctla-4 And Anti-Pd-1 Blockade In Rare Tumors (Dart) Swog S1609: Pancreatic Neuroendocrine Neoplasm (Pnen) Cohort, Sandip Pravin Patel, Jillian Fisher, Young Kwang Chae, Luisa Solis Soto, Anup Kasi, Bhavana Konda, Mark Walshauser, Edwin Parra, Jiexin Zhang, Caroline Duault, Edgar Gonzalez-Kozlova, Ganiraju Manyam, Jianhua Zhang, Hong Chen, Dzifa Yawa Duose, Caddie Laberiano Fernandez, Raja Luthra, Gheath Al-Atrash, Seunghee Kim-Schulze, Holden T Maecker, Ignacio I Wistuba, Sacha Gnjatic, J Jack Lee, Jianjun Zhang, Christine M Magner, Helen X Chen, Elad Sharon, Megan Othus, Christopher W Ryan, Charles Blanke, Cara L Haymaker, Razelle Kurzrock

Faculty, Staff and Student Publications

Purpose: SWOG S1609 Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) studied the efficacy of ipilimumab combined with nivolumab across multiple rare tumor types. We report the results of the pancreatic neuroendocrine neoplasm (PNEN) cohort.

Experimental design: Treatment consisted of ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously every 2 weeks. The primary endpoint was overall response rate (ORR) (Response Evaluation Criteria In Solid TumorsRECIST V.1.1). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and toxicity. Clinical benefit rate (includes ORR plus stable disease (SD)>6 months was examined. Correlative …

"Holy Cow, Where Do I Sign Up?" Attitudes Of Military Veterans Toward Epigenomic Biomarker Toxic Exposure Testing, Stacey Pereira, Calvin Apodaca, Kyle Slominski, Rachele K Lipsky, Cristian Coarfa, Cheryl L Walker, Amy L Mcguire, Lea Steele, Drew A Helmer

Center for Medical Ethics and Health Policy Staff Publications

Introduction: After the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics Promise to Address Comprehensive Toxics (PACT) Act in 2022, there has been a great interest in studying toxic exposures encountered during military service. Development of epigenomic biomarkers for exposures could facilitate understanding of exposure-related health effects, but such testing could also provide unwanted information.

Materials and methods: We explored attitudes toward epigenomic biomarker research and the potential to test for past exposures using semistructured interviews with Veterans (n = 22) who experienced potentially harmful exposures.

Results: Twenty Veterans said they would hypothetically want to receive …

Spinoplastic Surgery: A Review Of Techniques, Indications, And Optimal Patient Selection, Daniel Vernik, Camryn Payne, Krishna Sinha, Casey Martinez, Walter Nicholas Jungbauer, Jonathan L Jeger, Michael Bohl, Alexander E Ropper, Sebastian Winocour, Edward Reece

Faculty, Staff and Students Publications

Background/Objectives: Spinoplastic surgery is an emerging multidisciplinary field developed to address and reduce the complication of pseudoarthrosis following complex spinal reconstructions. While the number of spinal fusion procedures continues to rise every year, fusion failure rates remain as high as 40%. Although pseudoarthrosis may not always manifest clinically, it remains a leading cause of persistent pain and need for subsequent revision surgeries. The multidisciplinary collaboration between spine and plastic surgeons in spinoplastic surgery has therefore emerged as a proactive strategy aimed at preventing complications, particularly in patients identified as high-risk for pseudoarthrosis. As the patient population expands and spinoplastic surgery …

Lurasidone For Pediatric Bipolar Disorder: A Systematic Review, Alexia Koukopoulos, Claudia Calderoni, Georgios D Kotzalidis, Tommaso Callovini, Lorenzo Moccia, Silvia Montanari, Gianna Autullo, Alessio Simonetti, Mario Pinto, Giovanni Camardese, Gabriele Sani, Delfina Janiri

Faculty, Staff and Students Publications

Background/Objectives: Lurasidone ((3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione) is a second-generation antipsychotic approved for schizophrenia and mood disorders. Adolescents and children with bipolar disorder receive treatments that expose them to weight gain and metabolic syndrome. Lurasidone is relatively free from such side effects, so it may constitute a useful alternative for the treatment of these patients. We focused on the use of lurasidone in children and adolescents with bipolar disorder.

Methods: On 11 June 2025, we used the following strategy on PubMed: lurasidone AND ("bipolar disorder" OR "bipolar depression" OR mania OR manic). We filtered for humans and ages 0-18 years and included …

Ifi16 Mediates Deacetylation Of Kshv Chromatin Via Interaction With Nurd And Sin3a Co-Repressor Complexes, Anandita Ghosh, Bala Chandran, Arunava Roy

School of Medicine Faculty Publications

IFI16 is a well-characterized nuclear innate immune DNA sensor that detects foreign dsDNA, including herpesviral genomes, to activate the inflammasome and interferon pathways. Beyond immune signaling, IFI16 also functions as an antiviral restriction factor, promoting the silencing of invading viral genes through transcriptional and epigenetic mechanisms. We recently demonstrated another role of IFI16, in which it interacts with and recruits the class I histone deacetylases, HDAC1 and 2, to the KSHV latency protein LANA, modulating its acetylation and function. In this study, we asked whether these IFI16-HDAC1/2 interactions contribute to broader epigenetic regulation of the KSHV chromatin. Our findings reveal …

Obesity And Its Effect On Work Performance, Erin Lajoie

Lynchburg Journal of Medical Science

This research aims to examine how obesity affects work productivity and performance and how companies can support their employees diagnosed with obesity. Obesity is a growing global health concern that has significant implications for decreased workplace productivity and performance. Obesity is considered a chronic complex disease often associated with hypertension (HTN), type-II diabetes mellitus (T2DM), and heart disease that can lead to overall increases in healthcare costs for employers through increased absenteeism, presenteeism, and decreased efficiency. A systemic literature search was completed using PubMed, Cochrane Library, and Google Scholar, identifying multiple journal articles about obesity and productivity in the workplace …

Correction: Identification Of A Fusobacterial Rna-Binding Protein Involved In Host Small Rna-Mediated Growth Inhibition, Pu-Ting Dong, Mengdi Yang, Jie Hu, Lujia Cen, Peng Zhou, Difei Xu, Peng Xiong, Jiahe Li, Xuesong He

Faculty, Staff and Student Publications

No abstract provided.

Author Correction: Beta Activity In Human Anterior Cingulate Cortex Mediates Reward Biases, Jiayang Xiao, Joshua A Adkinson, John Myers, Anusha B Allawala, Raissa K Mathura, Victoria Pirtle, Ricardo Najera, Nicole R Provenza, Eleonora Bartoli, Andrew J Watrous, Denise Oswalt, Ron Gadot, Adrish Anand, Ben Shofty, Sanjay J Mathew, Wayne K Goodman, Nader Pouratian, Xaq Pitkow, Kelly R Bijanki, Benjamin Hayden, Sameer A Sheth

Faculty, Staff and Students Publications

No abstract provided.

A Conditional Point Cloud Diffusion Model For Deformable Liver Motion Tracking Via A Single Arbitrarily-Angled X-Ray Projection, Jiacheng Xie, Hua-Chieh Shao, Yunxiang Li, Shunyu Yan, Chenyang Shen, Jing Wang, You Zhang

Faculty, Staff and Student Publications

Objective. Deformable liver motion tracking using a single x-ray projection enables real-time motion monitoring and treatment intervention. We introduce a conditional point cloud diffusion (PCD) model-based framework for accurate and robust liver motion tracking from arbitrarily angled single x-ray projections. Approach. We propose a conditional PCD model for liver motion tracking (PCD-Liver), which estimates volumetric liver motion by solving deformable vector fields (DVFs) of a prior liver surface point cloud, based on a single x-ray image. It is a patient-specific model of two main components: a rigid alignment model to estimate the liver’s overall shifts, and a conditional PCD …

Anti-Transforming Growth Factor-Β Treatment Shows Increased Bone Mass And Strength In A Novel Mouse Model For Osteogenesis Imperfecta Type I, Ellen Busschers, Yuqing Chen-Everson, Mary Adeyeye, I-Wen Song, Emily Busse, Alexis Castellon, Oscar Ruiz, Nicole Meyers, Yangjin Bae, Catherine Ambrose, Brendan Lee

Faculty, Staff and Students Publications

Anti-transforming growth factor beta (TGF-β) is a promising approach for the treatment of osteogenesis imperfecta (OI). To date, preclinical and clinical studies for the use of anti-TGF-β therapy have focused on moderate to severe OI caused by qualitative defects in collagen. However, the majority of OI patients are represented by type I OI. Mutations resulting in the haploinsufficiency of type I collagen is the cause of OI type I in the majority of patients. To study the effect of anti-TGF-β therapy in type I OI, we generated a novel mouse model for OI type I. CMV-CRE mice were crossed to …

Short-Term Efficacy And Safety Of Nondamaging Retinal Laser Therapy For Retinitis Pigmentosa-Associated Cystoid Macular Edema, Seda Çevi̇k Kaya, Mehmet Çitirik, Mevlüt Yilmaz, Eyüpcan Şensoy

Turkish Journal of Medical Sciences

Background/aim: To evaluate the short-term efficacy and safety of nondamaging retinal laser therapy (NRT) for retinitis pigmentosa-associated cystoid macular edema (RP-CME) and analyze anatomical and functional outcomes.

Materials and methods: A retrospective case series of 40 eyes from 30 patients with RP-CME was conducted. The patients underwent NRT using a PASCAL laser system with endpoint management (EpM) software. Central macular thickness (CMT) and best-corrected visual acuity (BCVA) were assessed at baseline and 2 months posttreatment. Long-term follow-up data, including recurrence rates were also reviewed.

Results: At the 2-month follow-up, NRT significantly reduced mean CMT by 79.7 μm (p < 0.001) and improved BCVA by 0.10 LogMAR (p < 0.001). Complete resolution of CME was observed in 30% of the eyes, while 52.5% experienced recurrence within 6 months. Unilateral cases exhibited greater CMT reductions than bilateral cases (p < 0.05). No retinal damage from the laser was observed. The long-term sustainability of these effects remains unclear, and repeated treatments have not yet been assessed.

Conclusion: NRT …

Thermal Compensation Algorithm In Manoscan™ High-Resolution Esophageal Manometry: Does It Really Affect Manometry Metrics And Final Diagnosis?, Ekrem Aslan, Erdem Akbal

Turkish Journal of Medical Sciences

Background/aim: The accuracy of pressure measurements with ManoScan™ high-resolution manometry (HRM) catheters decreases due to the development of pressure drift (PD) resulting from variations between room and body temperature. The corrective algorithm called thermal compensation (TC), added to the manometry software program by the manufacturer is used to prevent the development of PD. To date, no studies have demonstrated that PD leads to changes in manometry metrics and/or clinical diagnosis. The present study aims to demonstrate the impact of the TC algorithm on HRM metrics and final diagnosis.

Materials and methods: Records of 124 consecutive esophageal HRM studies with ManoScan™ …

Administration Of Adipose Tissue-Derived Mesenchymal Stem Cells And Bone Marrow-Derived Mesenchymal Stem Cells In Anosmic Mice, Burak Hazir, Alper Ceylan, Emi̇n Ümi̇t Bağriaçik, Duygu Dayanir, Betül Öğüt, Ni̇han Örüklü, Mücahi̇t Yalçin, Berkay Şi̇mşek, Muammer Meli̇h Şahi̇n

Turkish Journal of Medical Sciences

Background/aim: Anosmia, a serious condition that affects the sense of smell, has no universally agreed-upon treatment. Adult stem cells are considered a potential option for treating anosmia. This study aims to evaluate the efficacy of mesenchymal stem cells derived from different tissues in an anosmic mouse model induced by 3-methylindole (3-MI).

Materials and methods: In our study, 36 mice with 3-MI-induced anosmia were divided into subgroups. Anosmia was confirmed by performing a food-finding test (FFT) in each group. Intranasal phosphate-buffered saline was administered to the first group, adipose tissue-derived mesenchymal stem cells (ADSCs) to the second group, and bone marrow-derived …

Erratum To " Evaluation Of Clinical Features And Treatment Modality Of Pediatric Patients With Steven Johnson Syndrome/Toxic Epidermal Necrolysis: A Single-Center Experience " [ Turkish Journal Of Medical Sciences 55 2 461 469], Funda Ayteki̇n Güveni̇r

Turkish Journal of Medical Sciences

In the original article, the ORCID of one of the co-authors, Hatice Irmak ÇELİK, was incorrectly reported by the corresponding author. At the request of the authors, the ORCID has been corrected to reflect the accurate information. This correction does not affect the content or conclusions of the article. The authors apologize for this oversight.

Link to the original article: https://doi.org/10.55730/1300-0144.5990

Expert Opinion On Clinical Presentation, Diagnosis And Treatment Of Infantile Onset Pompe Disease: A Delphi Study In Türkiye, Eki̇n Özsaydi Aktaşoğlu, Asli İnci̇, Ridvan Murat Öktem, Gürsel Bi̇beroğlu, İlyas Okur, Fati̇h Süheyl Ezgü, Fi̇li̇z Başak Cengi̇z Ergi̇n, Abdurrahman Akgün, Nur Arslan, Hali̇l İbrahi̇m Aydin, Ayşe Ergül Bozaci, Mahmut Çoker, Fatma Tuba Emi̇noğlu, Meli̇ke Ersoy, Emi̇ne Göksoy, Banu Kadioğlu Yilmaz, Mehtap Kağnici, Mustafa Kiliç, Nesli̇han Önenli̇ Mungan, Burcu Öztürk Hişmi̇, Pembe Soylu Üstkoyuncu, Ayşegül Tokatli, Ayşe Çi̇ğdem Aktuğlu Zeybek, Berrak Bi̇lgi̇ner Gürbüz, Sevi̇l Dorum, Di̇lek Güneş, Çi̇ğdem Seher Kasapkara, Sebi̇le Kilavuz, Erdoğan Soyuçen, Peli̇n Teke Kisa, Özlem Ünal Uzun, Fatma Derya Bulut, Songül Gökay, Selen Has Özhan, Deni̇z Kor, Aynur Küçükcongar Yavaş, Fi̇gen Özçay, Yilmaz Yildiz, Harun Yildiz, Leyla Tümer

Turkish Journal of Medical Sciences

Background/aim: Pompe disease (acid maltase deficiency, glycogen storage disease type II, OMIM #606800) is an autosomal recessive disorder characterized by lysosomal acid-α-glucosidase deficiency. The infantile-onset type of the disease is mainly characterized by cardiomegaly, hypotonia, and a high mortality rate. This study aimed to create a national consensus about infantile-onset Pompe disease (IOPD) to raise awareness among clinicians and standardize diagnosis and treatment approaches in Türkiye.

Materials and methods: The Gazi University Division of Metabolic Diseases and Nutrition developed this expert opinion consensus and expanded it to include metabolism specialists across Türkiye. A systematic literature review was performed, and the …

Long-Term Results Of Branch Retinal Vein Occlusion: 5-Year Follow-Up, Ilkay Kilic Muftuoglu, Natasha Mayer, Katherina Du, Catalina Feistritzer, Elise Barberis, Sashwanti Mohan, Jay Chhablani

Turkish Journal of Medical Sciences

Background/aim: This study aimed to report the 5-year outcomes of patients with newly diagnosed branch retinal vein occlusion (BRVO).

Materials and methods: A retrospective review of patient charts was conducted. Data on central macular thickness (CMT), best-corrected visual acuity (BCVA), photoreceptor integrity, number of intravitreal (IV) antivascular endothelial growth factor (anti- VEGF) injections administered, and treatment regimen were assessed.

Results: Ninety-seven eyes from individual patients with a mean age of 70.90 ± 11.49 (38–92) were included. The mean BCVA improved, and the mean CMT decreased at all follow-up visits following treatment (p < 0.05). Thirty-two eyes (33%) gained 3 lines of BCVA at the five-year follow-up. The mean number of total IV anti-VEGF injections administered was 19 ± 13.35 (1–49) during the five-year period, and 27.83% of patients received rescue laser treatment. Fifty-four percent of eyes received three consecutive monthly loading doses of IV anti-VEGF injections. The mean change in BCVA in the loading dose (+) group was significantly greater than in the loading dose (–) group at 1-year and subsequent visits. The loading dose (+) group showed a significantly greater reduction in CMT compared to the loading dose (–) group. The mean estimated time for BCVA to decline by ≥3 lines was 117 ± 8.74 months (95% CI = 100.21–134.51)

Conclusion: Anti-VEGF treatment was effective in improving anatomical …

Diagnosis Of Knee Joint Invasion In Patients With Osteosarcoma: The Value Of Direct And Indirect Mri Findings, İpek Tamsel, Hüseyi̇n Kaya, Orkhan Aghamirzayev, Oğuz Di̇mdork, Başak Doğanavşargi̇l, Mehmet Argin, Dündar Sabah

Turkish Journal of Medical Sciences

Background/aim: Osteosarcoma is the most common primary malignant bone tumor in adolescents, and the evaluation of joint invasion with MRI is important for treatment planning. This study aimed to investigate the diagnostic value of MRI findings (direct and indirect) for joint invasion in patients diagnosed with osteosarcoma of the knee region.

Materials and methods: The MRI evaluations of 50 knee osteosarcoma patients who underwent surgical resection between 2006 and 2018 were reviewed retrospectively by two radiologists and an orthopedic oncologist. The presence of intrasynovial tumor tissue, intra-articular destruction of cartilage or bone, and invasion of the capsular and cruciate ligament …

Vitamin D Deficiency And Surgical Cellulose Mimicking Parathyroid Adenomaafter Initial Parathyroidectomy, Mustafa Şahi̇n, Volkan Genç, Koray Ceyhan, Demet Corapcioglu

Turkish Journal of Medical Sciences

Background/aim: Primary hyperparathyroidism is a condition characterized by an excessive production of parathyroid hormone primarily resulting from the presence of an adenoma or hyperplasia of the parathyroid glands.

Materials and methods: A 45-year-old woman who had previously experienced high levels of calcium in her blood and abnormally elevated parathyroid hormone levels underwent surgical removal of the left parathyroid gland. Following surgery, she exhibited high levels of parathyroid hormone along with normalized calcium levels and persistent fatigue. Ultrasound imaging showed a hypoechoic mass on the left side, which was initially considered to be a recurrent parathyroid tumor.

Results: A comprehensive assessment, …

Evaluation And Validation Of 3d-Printed Anatomical Urinary System Model And Virtual Reality Rirs Simulators In Rirs Training: A Comparative Study, Mehmet Ezer, Tahsi̇n Batuhan Aydoğan, Lazaros Tzelves, Andreas Skolarikos, Mehmet Uslu, Kemal Sarica, Emre Huri̇

Turkish Journal of Medical Sciences

Background/aim: This study evaluates the use of a 3D-printed anatomical urinary system model (3D-AUSM) and a Virtual Reality RIRS Simulator (VRRS), for training in RIRS, based on real user feedback.

Materials and methods: The 3D-AUSM was created using cadaver CT and MRI scans, and the data was transferred to a VR environment for simulation. A total of 43 inexperienced urology trainees participated in the theoretical phase of the RIRS training program. Of these, 32 trainees (Group T) who passed a proficiency exam proceeded to the hands-on training phase with the 3D-AUSM and VRRS models. Additionally, 17 experienced surgeons (Group S) …

Medicolegal Evaluation Of Pediatric Patients With Injection Neuropathy, Hizir Asliyüksek, Caner Beşkoç, Ömer Faruk Şi̇mşeker, Ni̇han Hande Akçakaya, Adem Karbuz

Turkish Journal of Medical Sciences

Background/aim: Injection neuropathy (IN) is a rare but preventable form of iatrogenic nerve injury, particularly affecting the sciatic nerve when intramuscular injections are administered incorrectly. While IN is uncommon in high-income countries, it remains a sig- nificant public health issue in Türkiye, especially in pediatric populations. The aim of this study is to evaluate pediatric IN cases referred to the Council of Forensic Medicine and highlight medicolegal aspects to inform clinical and legal preventive strategies.

Materials and methods: We retrospectively analyzed 67 pediatric cases (age range: 1–17 years; mean age: 10.5 years; 57 boys, 10 girls) referred to the Council …

Usp37 Counteracts Hltf To Protect Damaged Replication Forks And Promote Survival Of Brca1-Deficient Cells And Parp Inhibitor Resistance, Mengfan Tang, Siting Li, Ziqiang Zhu, Chao Wang, Shuai Ding, Huimin Zhang, Min Huang, Sarah Keast, Zhen Chen, Ling Yin, Litong Nie, Dan Su, Xu Feng, Junjie Chen

Faculty, Staff and Student Publications

Poly(ADP-ribose) polymerase inhibitors (PARPi) have greatly improved survival of cancer patients harboring BRCA1 mutations. However, therapy resistance develops via either restoration of homologous recombination or replication fork stabilization. Therapeutic targets to overcome PARPi resistance are critically needed. We identified the deubiquitinase USP37 as a key determinant of PARPi toxicity in BRCA1-deficient cells via whole-genome CRISPR screens. USP37 ablation enhanced PARPi sensitivity in BRCA1-deficient cells and also overcame PARPi resistance due to 53BP1 loss. USP37 interacts with and deubiquitinates replication protein A (RPA) at stalled replication forks to limit excessive RPA accumulation, progressive RPA exhaustion, and the conversion of RPA-coated single-stranded …

Protocol To Analyze Trna And Rrna Processing Using Biotin-Labeled Probes, Sseu-Pei Hwang, Katherine Barondeau, Catherine Denicourt

Faculty, Staff and Student Publications

Mature tRNAs and rRNAs are derived from larger precursor transcripts through intricate endo- and exonuclease processing steps. Here, we present a protocol to analyze rRNA and tRNA processing using total RNA extracted from human cells. We describe steps for separating RNA by denaturing electrophoresis, followed by northern blotting. We detail procedures for detecting pre-rRNA intermediates or specific tRNA species using biotin-labeled probes imaged via fluorescence or chemiluminescence. This non-radioactive, high-sensitivity assay enables the investigation of rRNA and tRNA expression dynamics. For complete details on the use and execution of this protocol, please refer to Hwang et al.

Characterization And Clinical Implications Of P53 Dysfunction In Patients With Myelodysplastic Syndromes, Matteo Zampini, Elena Riva, Luca Lanino, Elisabetta Sauta, Rita Antunes Dos Reis, Rosa Maria Andres Ejarque, Giulia Maggioni, Alberto Termanini, Alessandra Merlotti, Alessia Campagna, Lorenzo Dall'olio, Austin Kulasekararaj, Michela Calvi, Clara Di Vito, Arturo Bonometti, Daoud Rahal, Giorgio Croci, Emanuela Boveri, Umberto Gianelli, Maurilio Ponzoni, Rossella Caselli, Serena Albertazzi, Gabriele Todisco, Marta Ubezio, Laura Crisafulli, Alessandro Frigo, Enrico Lugli, Ettore Mosca, Pamela Acha, Serena Ghisletti, Francesco Nicassio, Armando Santoro, Maria Diez-Campelo, Francesc Solé, Lionel Ades, Uwe Platzbecker, Valeria Santini, Pierre Fenaux, Torsten Haferlach, David Sallman, Guillermo Garcia-Manero, Domenico Mavilio, Daniel Remondini, Gastone Castellani, Saverio D'Amico, Amer M Zeidan, Rami Komrokji, Shahram Kordasti, Francesca Ficara, Matteo Giovanni Della Porta, Calr Consortium

Faculty, Staff and Student Publications

Purpose: Tumor Protein 53 (p53) expressed from gene TP53 is a seminal tumor suppressor. We aimed to characterize mutational and nonmutational mechanisms of p53 dysfunction in myelodysplastic syndromes (MDS) and to investigate their clinical effect.

Patients and methods: We analyzed a cohort of 6,204 patients with MDS and subsets of patients with available information on RNA sequencing of tumor cells (n = 109), high-dimensional phenotype of immune cells (n = 77), and multiomics analysis (RNA sequencing and proteomics) on single cells (n = 15). An independent validation was performed on 914 patients.

Results: Biallelic TP53 inactivation was a powerful driver …

Multi-Ancestry Genome-Wide Association Analyses Incorporating Snp-By-Psychosocial Interactions Identify Novel Loci For Serum Lipids, Amy R Bentley, Michael R Brown, Solomon K Musani, Karen L Schwander, Thomas W Winkler, Mario Sims, Tuomas O Kilpeläinen, Hugues Aschard, Traci M Bartz, Lawrence F Bielak, Jin-Fang Chai, Kumaraswamy Naidu Chitrala, Nora Franceschini, Mariaelisa Graff, Xiuqing Guo, Fernando P Hartwig, Andrea R V R Horimoto, Elise Lim, Yongmei Liu, Alisa K Manning, Ilja M Nolte, Raymond Noordam, Melissa A Richard, Albert V Smith, Yun Ju Sung, Dina Vojinovic, Rujia Wang, Yujie Wang, Mary F Feitosa, Sarah E Harris, Leo-Pekka Lyytikäinen, Giorgio Pistis, Rainer Rauramaa, Peter J Van Der Most, Erin Ware, Stefan Weiss, Wanqing Wen, Lisa R Yanek, Dan E Arking, Donna K Arnett, Christie Ballantyne, Eric Boerwinkle, Yii-Der Ida Chen, Martha L Daviglus, Lisa De Las Fuentes, Paul S De Vries, Joseph A C Delaney, Amanda M Fretts, Lynette Ekunwe, Jessica D Faul, Linda C Gallo, Sami Heikkinen, Georg Homuth, M Arfan Ikram, Carmen R Isasi, Jost Bruno Jonas, Liisa Keltikangas-Järvinen, Pirjo Komulainen, Aldi T Kraja, Jose E Krieger, Lenore Launer, Lifelines Cohort Study, Jianjun Liu, Kurt Lohman, Annemarie I Luik, Ani W Manichaikul, Pedro Marques-Vidal, Yuri Milaneschi, Stanford E Mwasongwe, Jeffrey R O'Connell, Kenneth Rice, Stephen S Rich, Pamela J Schreiner, Lars Schwettmann, James M Shikany, Xiao-Ou Shu, Jennifer A Smith, Harold Snieder, Nona Sotoodehnia, E Shyong Tai, Kent D Taylor, Lesley Tinker, Michael Y Tsai, André G Uitterlinden, Cornelia M Van Duijn, Diana Van Heemst, Melanie Waldenberger, Robert B Wallace, Hwee-Lin Wee, David R Weir, Wen-Bin Wei, Ko Willems Van Dijk, Gregory Wilson, Jie Yao, Kristin L Young, Xiaoyu Zhang, Wei Zhao, Xiaofeng Zhu, Alan B Zonderman, Ian J Deary, Christian Gieger, Hans Jörgen Grabe, Timo A Lakka, Terho Lehtimäki, Albertine J Oldehinkel, Martin Preisig, Ya-Xing Wang, Wei Zheng, Michele K Evans, Michael Province, James Gauderman, Vilmundur Gudnason, Catharina A Hartman, Bernardo L Horta, Sharon L R Kardia, Charles Kooperberg, Ching-Ti Liu, Dennis O Mook-Kanamori, Brenda Wjh Penninx, Alexandre C Pereira, Patricia A Peyser, Bruce M Psaty, Jerome I Rotter, Xueling Sim, Kari E North, Dabeeru C Rao, Laura Bierut, Clint L Miller, Alanna C Morrison, Charles N Rotimi, Myriam Fornage, Ervin R Fox

Faculty, Staff and Student Publications

Serum lipid levels, which are influenced by both genetic and environmental factors, are key determinants of cardiometabolic health and are influenced by both genetic and environmental factors. Improving our understanding of their underlying biological mechanisms can have important public health and therapeutic implications. Although psychosocial factors, including depression, anxiety, and perceived social support, are associated with serum lipid levels, it is unknown if they modify the effect of genetic loci that influence lipids. We conducted a genome-wide gene-by-psychosocial factor interaction (G×Psy) study in up to 133,157 individuals to evaluate if G×Psy influences serum lipid levels. We conducted a two-stage meta-analysis …

X-Linked Hypophosphatemia Management In Children: An International Working Group Clinical Practice Guideline., Dalal S. Ali, Thomas O. Carpenter, Erik A. Imel, Leanne M. Ward, Natasha M. Appelman-Dijkstra, Catherine Chaussain, Suzanne M. Jan De Beur, Pablo Florenzano, Hajar Abu Alrob, Rana Aldabagh, R Todd Alexander, Farah Alsarraf, Signe Sparre Beck-Nielsen, Martin Biosse-Duplan, Rachel K. Crowley, Karel Dandurand, Guido Filler, Lisa Friedlander, Seiji Fukumoto, Claudia Gagnon, Paul Goodyer, Corinna Grasemann, Chelsey Grimbly, Salma Hussein, Muhammad K. Javaid, Sarah Khan, Aneal Khan, Anna Lehman, Willem F. Lems, E Michael Lewiecki, Ciara Mcdonnell, Reza D. Mirza, Emmett Morgante, Archibald Morrison, Anthony A. Portale, Christina Rao, Yumie Rhee, Eric T. Rush, Heide Siggelkow, Sotirios Tetradis, Laura Tosi, Gordon Guyatt, Maria Luisa Brandi, Aliya A. Khan

Manuscripts, Articles, Book Chapters and Other Papers

CONTEXT: An International Working Group (IWG) developed new guidelines on the diagnosis, evaluation, management, and monitoring of X-linked hypophosphatemia (XLH) in children. Over the past 5 years, important advances have occurred in our understanding of the presentation, complications, and treatment of XLH.

METHODS: A group of 50 international experts in XLH from Canada, the United States, Europe, Asia, and South America, along with methodology experts and a patient partner, held 18 teleconference meetings in 2023-2024. These meetings addressed key issues regarding diagnosing, evaluating, managing, and monitoring XLH in children. Two systematic reviews were conducted to examine the impact of burosumab …

The Maturity-Onset Diabetes Of The Young (Mody) Calculator Overestimates Mody Probability In Hispanic Youth, Guido Alarcon, Anh Nguyen, Angus Jones, Beverley Shields, Maria J Redondo, Mustafa Tosur

Children’s Nutrition Research Center Staff Publications

Context: The applicability of the maturity-onset diabetes of the young (MODY) risk calculator to non-White European populations remains unknown.

Objective: We aimed to test its real-world application in Hispanic youth.

Methods: We conducted a retrospective chart review of Hispanic youth (< 23 years) with diabetes (n = 2033) in a large pediatric tertiary care center in the United States. We calculated MODY probability for all subjects, splitting them into 2 cohorts based on the original model: individuals who were started on insulin within 6 months of diabetes diagnosis (Cohort 1) and those who were not (Cohort 2).

Results: Cohort 1 consisted of 1566 individuals (median age [25p, 75p]: 16 [13, 19] years, 49% female), while Cohort 2 comprised 467 youth (median age [25p, 75p]: 17 [15, 20] years, 62% female). The mean MODY probability was 5.9% and 61.9% in Cohort 1 and Cohort 2, respectively. The mean probability for both cohorts combined was 18.8%, suggesting an …

Atad3 Is Essential For Mitochondrial Permeability Transition Pore Opening And Cardiac Ischemia Reperfusion Injury, Dexter Robichaux, Sual J Lopez, Arielys Mendoza, Daniel Ramirez, Suh-Chin J Lin, Jeffery D Molkentin, Pablo M Peixoto, Jason Karch

Faculty, Staff and Students Publications

The molecular identity of the mitochondrial permeability transition pore (mPTP) has remained elusive since the discovery of its existence over 75 years ago. Despite the numerous candidate proteins proposed, none have withstood genetic ablation, leaving them relegated to auxiliary regulatory roles. To date, no essential mPTP component has been identified. Here, we establish ATAD3 as the first essential component of the mPTP. Genetic deletion of Atad3 in cardiomyocytes and hepatocytes renders heart and liver mitochondria incapable of undergoing Ca 2+ -induced mPTP-dependent swelling. Moreover, these mitochondria exhibit the highest Ca 2+ retention capacity ever reported following genetic perturbation of the …

Clinical And Radiological Features Of Atypical Adrenal Masses-A Multicenter Retrospective Study, Vania Balderrama-Brondani, Ruaa Al-Ward, Katja Kiseljak-Vassiliades, Lauren Fishbein, Danielle Dawes, Oksana Hamidi, Reza Pishdad, Juan Pablo Perdomo Rodriguez, Mohamad Anas Sukkari, Joseph R Grajo, Hans Kumar Ghayee, Sara Bedrose, Roland L Bassett, Amir H Hamrahian, Mouhammed Amir Habra

Faculty, Staff and Students Publications

Context: The natural history and malignant potential of cases classified as atypical adrenal masses (AAMs) are unknown.

Objective: To describe the radiological characteristics and clinical outcomes of AAMs.

Design and participants: A multicenter retrospective study. Patients ≥18 years old with AAMs [diameter of 10-39 mm on first imaging study and pre-contrast attenuation of >10 Hounsfield units (HU) on computed tomography] were studied. We excluded adrenal metastasis, pheochromocytoma, sarcoma, lymphoma, infiltrative lesions, and adrenal hemorrhage, as well as patients with genetic predisposition to adrenal neoplasms. Data are presented as percentages and median values with interquartile ranges (IQRs).

Results: We included 217 …

The Tumor Suppressor Hnrnpk Induces P53-Dependent Nucleolar Stress To Drive Ribosomopathies, Pedro Aguilar-Garrido, María Velasco-Estévez, Miguel Ángel Navarro-Aguadero, Álvaro Otero-Sobrino, Marta Ibáñez-Navarro, Miguel Ángel Marugal, María Hernández-Sánchez, Prerna Malaney, Ashley Rodriguez, Oscar Benitez, Xiaroui Zhang, Marisa Jl Aitken, Alejandra Ortiz-Ruiz, Diego Megías, Manuel Pérez, Gadea Mata, Jesús Gomez, Miguel Lafarga, Orlando Domínguez, Osvaldo Graña-Castro, Eduardo Caleiras, Pilar Ximénez-Embun, Marta Isasa, Paloma Jimena De Andres, Sandra Rodríguez-Perales, Raúl Torres-Ruiz, Enrique Revilla, Rosa María García-Martín, Daniel Azorín, Josune Zubicaray, Julián Sevilla, Oleksandra Sirozh, Vanesa Lafarga, Joaquín Martínez-López, Sean M Post, Miguel Gallardo

Faculty, Staff and Student Publications

The nucleolus is a membraneless organelle and an excellent stress sensor. Any changes in its architecture or composition lead to nucleolar stress, resulting in cell cycle arrest and interruption of ribosomal activity, critical factors in aging and cancer. In this study, we identified and described the pivotal role of the RNA-binding protein HNRNPK in ribosome and nucleolar dynamics. We developed an in vitro model of endogenous HNRNPK overexpression and an in vivo mouse model of ubiquitous HNRNPK overexpression. These models showed disruptions in translation as the HNRNPK overexpression caused alterations in the nucleolar structure, resulting in p53-dependent nucleolar stress, cell …