Digital Commons Network^™

Self-Clustering Of Three Cbx2 Molecules Drives Prc2 To Promote Facultative Heterochromatinization Of Polycomb Target Genes, Steven Ingersoll, Abby Trouth, J Carlos Angel, Xinlong Luo, Axel Espinoza, Joey Wen, Chengjie Zhu, Joseph Tucker, Kalkidan Astatike, Christopher J Phiel, Hatim Sabaawy, Tatiana G Kutateladze, Tao P Wu, Tingting Yao, Chao Lu, Srinivas Ramachandran, Xiaojun Ren

Faculty, Staff and Students Publications

Phase separation is increasingly recognized in facultative heterochromatinization of Polycomb target genes; however, the mechanisms underlying this process remain obscure. Using single-molecule imaging and tracking, we show that individual condensates in mouse embryonic stem cells (mESCs) contain approximately 3 CBX2 molecules and numerous Polycomb repressive complex (PRC)1 and PRC2 subunits and indicate that the composition and dynamics of condensates are developmentally regulated. We reveal that CBX2 clusters PRC2 and controls the spatial distribution of both PRC2 and H3K27me3. Using genomic approaches, we demonstrate that CBX2 binds to condensate initiation sites, which are enriched for PRC2 nucleation sites. CBX2 deletion causes …

Immunotherapy Of Tsa-1.C4 Or In Combination With Bnz Confers Protection Against Trypanosoma Cruzi Infection With A Distinct Cytokine Response, Landy Magaly Pech-Pisté, Victor Dzul-Huchim, Christian Florian Teh-Poot, Fabian Gusovsky, Kathryn Jones, Peter Hotez, Liliana Estefanía Villanueva-Lizama, Maria Elena Bottazzi, Jaime Ortega-Lopez, Julio Vladimir Cruz-Chan

Faculty, Staff and Students Publications

Chagas disease is a poverty-related neglected tropical disease caused by the protozoan Trypanosoma cruzi affecting approximately 6.3 million people, predominantly in the Americas. Approximately 30% of T. cruzi infections progress to chronic cardiomyopathy and 10% of these cases end in death from cardiac failure. The first-line drug Benznidazole (BNZ) require a prolonged treatment regimen and can be highly toxic. Here, we evaluate a therapeutic vaccine in T. cruzi-infected mice, based on the recombinant Trypomastigote Surface Antigen 1 (TSA-1.C4) protein and the emulsified adjuvant E6020, and in combination with a suboptimal dose of BNZ. We observed a reduced burden parasite in …

Immunotherapy Of Tsa-1.C4 Or In Combination With Bnz Confers Protection Against Trypanosoma Cruzi Infection With A Distinct Cytokine Response, Landy Magaly Pech-Pisté, Victor Dzul-Huchim, Christian Florian Teh-Poot, Fabian Gusovsky, Kathryn Jones, Peter Hotez, Liliana Estefanía Villanueva-Lizama, Maria Elena Bottazzi, Jaime Ortega-Lopez, Julio Vladimir Cruz-Chan

Faculty, Staff and Students Publications

Chagas disease is a poverty-related neglected tropical disease caused by the protozoan Trypanosoma cruzi affecting approximately 6.3 million people, predominantly in the Americas. Approximately 30% of T. cruzi infections progress to chronic cardiomyopathy and 10% of these cases end in death from cardiac failure. The first-line drug Benznidazole (BNZ) require a prolonged treatment regimen and can be highly toxic. Here, we evaluate a therapeutic vaccine in T. cruzi-infected mice, based on the recombinant Trypomastigote Surface Antigen 1 (TSA-1.C4) protein and the emulsified adjuvant E6020, and in combination with a suboptimal dose of BNZ. We observed a reduced burden parasite in …

The Agreement Between Pulse Oximetry And Measured Arterial Oxygen Saturations In Postoperative Functionally Univentricular Patients, Fabio Savorgnan, Sebastian Acosta, Joshua Prabhu, Pranathi Pilla, Vikram Shah, Saul Flores, Rohit S Loomba

Faculty, Staff and Students Publications

Background: Pulse oximetry is widely used to estimate arterial oxygen saturation, yet accuracy may vary for a number of reasons. Data on children with functionally univentricular circulation are limited. The primary aim of this study was to evaluate the agreement between arterial oxygen saturation measured by blood gas and pulse oximetry in children with functionally univentricular circulations. Methods: A retrospective analysis was performed of paired arterial blood gas and pulse oximetry oxygen saturation measurements following Norwood, Glenn, or Fontan procedures. Signed difference was defined as arterial oxygen saturation by blood gas-arterial oxygen saturation by pulse oximetry. Bland-Altman analyses, …

Impact Of Long-Term Nitrogen Scavenger Therapy On Clinical Outcome In Individuals With Urea Cycle Disorders, Roland Posset, Friederike Epp, Sven F Garbade, Florian Gleich, Andrea L Gropman, Sandesh C S Nagamani, Georg F Hoffmann, Stefan Kölker, Matthias Zielonka

Faculty, Staff and Students Publications

Principles of long-term medical management in individuals with urea cycle disorders (UCDs) encompass (1) a low protein diet, (2) supplementation of arginine and/or citrulline along with essential amino acids, nutrients, vitamins and trace elements, and (3) use of nitrogen scavenging agents to reduce recurrent hyperammonemic events (HAEs). These principles aim at providing metabolic stability, elimimation of chronic complications, and achievement of normal development as well as growth. A retrospective comparative analysis was performed by studying 138 individuals with male ornithine transcarbamylase deficiency (mOTC-D), citrullinemia type 1 (CTLN1) and argininosuccinic aciduria (ASA) based on in vitro residual enzymatic activity for severity-adjustment. …

“Real-World Prognostic Performance Of Different Severe And Advanced Heart Failure Definitions: Data From The Swedish Heart Failure Registry”, Federica Guidetti, Lars H Lund, Lina Benson, Camilla Hage, Felix Lindberg, Christian Basile, Alessandro Villaschi, Francesca Musella, Davide Stolfo, Raffaele Scorza, Guillame Baudry, Charlotta Ljungman, Oscar Braun, Valeria Valente, Biykem Bozkurt, Marco Metra, Gianluigi Savarese

Faculty, Staff and Students Publications

Background: A valid definition of severe heart failure (HF) is essential for earlier identification, timely referral for advanced therapies, and to optimize clinical trial design.

Objectives: To assess the prevalence, prognostic performance, and 1-year outcomes associated with different definitions of severe and advanced HF (AdvHF) in patients with heart failure with reduced ejection fraction (HFrEF).

Methods: We included 15,153 patients with EF < 40%, HF duration >6 months, and no prior left ventricular assist device or heart transplant, from the Swedish Heart Failure Registry. Several definitions of severe/AdvHF were evaluated: a simplified Heart Failure Association (HFA) definition (NYHA III-IV, EF < 30%, ≥2 HF hospitalizations in 12 months), the GALACTIC-Severe-definition (NYHA III-IV, EF < 30%, ≥1 hospitalization in 6 months), and variations adding/removing criteria such as NT-proBNP levels and diuretic dose to the HFA-AdvHF definition. Predictive performance and 1-year outcomes were analyzed.

Results: The HFA-definition identified …

A Tibial Osteotomy Of The Medial Collateral Ligament Insertion To Improve Visualization Of The Medial Tibial Plateau: A Cadaveric Study, Kathryn A Barth, Ricardo R Tijerina, Adeet Amin, Avrey A Novak, Erik N Mayer, Sabir K Ismaily, John W Munz, Andrew M Choo, Timothy S Achor, Steven J Warner, Jonathan G Eastman, Patrick J Kellam

Faculty, Staff and Student Publications

Objectives: To compare visualization of the medial tibial plateau articular surface using three surgical approaches: medial collateral ligament (MCL) split, femoral epicondyle osteotomy of the MCL origin, and tibial osteotomy of the MCL insertion.

Methods: Seven matched pairs of fresh-frozen adult cadaveric lower extremity specimens (14 knee specimens total) with no evidence of previous surgery were utilized. Through a medial approach to the proximal tibia, the MCL split technique was performed followed by a sub-meniscal arthrotomy. Standardized distraction of the joint was applied using a universal distractor. A three-dimensional digitizer probe was utilized to map the visible articular surface. These …

Fungal Meningitis In Us Patients Who Received Epidural Anesthesia In Matamoros, Mexico, Dallas J Smith, Elizabeth Misas, Jeremy A W Gold, Nicole Evert, Thi Dang, Emilie Prot, Simone Godwin, Julieanna Rivas, Jessica Pearson, Lori Koenecke, Nirma D Bustamante, Maria Julia Marinissen, Gabriel Garcia Rodriquez, Irma López-Martínez, Caitlyn Lutfy, Samantha Williams, Axel A Vazquez Deida, Katrina M Byrd, Julian A Villalba, Sarah Reagan-Steiner, Lindsay Parnell, Lalitha Gade, Romney M Humphries, Nathan P Wiederhold, Charles Y Chiu, Joshua A Lieberman, Anastasia P Litvintseva, Tom Chiller, Luis Ostrosky-Zeichner, Fungal Meningitis Response Team

Faculty, Staff and Student Publications

Background: Fungal meningitis outbreaks are rare and entail high mortality rates. Beginning May 2023, we investigated fungal meningitis caused by Fusarium solani species complex occurring in US patients who received epidural anesthesia in Matamoros, Mexico.

Methods: Early epidemiological information suggested US patients with suspected fungal meningitis had undergone mostly cosmetic procedures under epidural anesthesia performed in 2 Matamoros clinics. US patients known to have received surgery at these clinics during 1 January-13 May 2023 (clinic closures date) were identified and notified by public health officials. Epidemiological and clinical data were used to update diagnostic and clinical guidance for outbreak response, …

Efficacy And Safety Of Approved Cellular Therapies And Bispecific Antibodies In Solid Tumors: The Current State, Rabab Zehra Jafry, Saba Bilal Qamar, Sohaib Irfan, Muhammad Abbas Abid, Virginia Mohlere, Neha Maithel, Syed Hassan Jafri, Sanjay Awasthi, Samer Srour, Irfan A Vaziri, Muhammad Bilal Abid

Faculty, Staff and Student Publications

Cancer immunotherapy is a broad term including naked antibodies, bispecific antibodies (BsAbs), immune-checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell (CAR-T) therapy, cancer vaccines, activated immune cells, and allogeneic hematopoietic cell transplantation. Recent advances in immune-engaging T-cell therapies have led to significant progress in novel treatments across various cancer types, resulting in prolonged patient survival, mainly in patients with hematologic malignancies. Several CAR T-cell constructs and BsAbs have been approved by regulatory authorities worldwide for relapsed, refractory leukemia, non-Hodgkin lymphoma, and multiple myeloma. Solid tumors are characterized by an immunosuppressive, fibroinflammatory tumor microenvironment (TME) and immune-suppressive cells, such as regulatory T-cells …

Visdb 20: A Manually Curated Resource Of Viral Integration Sites And Their Regulatory Maps In Human Diseases, Citu Citu, Ajeet Singh, Xinyi Liu, Mounika Ashannagari, Rinki Ratnapriya, Zhongming Zhao

Faculty, Staff and Student Publications

The integration of viral sequence into the human genome plays critical role in the onset of various diseases, especially cancers. To facilitate systematic analysis of these events, we present VISDB 2.0, an expanded and updated database of human viral integration sites (VISs). The current release contains more than 270,000 manually curated VISs derived from 209 peer-reviewed publications, covering 11 viruses, including four retroviruses and seven DNA viruses. This represents a 3.5-fold increase in VIS entries compared with the previous version. Each VIS record includes standardized genomic coordinates and annotations describing local genomic context, CpG islands, repetitive elements, chromosomal fragile sites, …

2026 Clinical Practice Guideline Update By The Infectious Diseases Society Of America And The Pediatric Infectious Diseases Society On The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age: The Use Of Tpa And Dnase Or Tpa Alone For Fibrinolysis, Shawn D St Peter, Krow Ampofo, Thomas Brogan, Michael D Cabana, Claudia Espinosa, Todd A Florin, Jeffrey S Gerber, Michelle Gill, Debra L Palazzi, Mark Sawyer, Angela M Statile, Derek J Williams, Sheena Patel, Mark I Neuman, Samir S Shah

Faculty, Staff and Students Publications

This paper is part of a larger clinical practice guideline on the diagnosis and management of parapneumonic effusion and empyema in children, developed by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. In this report, the panel provides recommendations for intrapleural fibrinolysis with tissue plasminogen activator (tPA) alone over tPA and dornase alfa (DNase) in children (3 months to 18 years) with complicated parapneumonic effusion and empyema. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according …

2026 Clinical Practice Guideline Update By The Infectious Diseases Society Of America And The Pediatric Infectious Diseases Society On The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age: The Choice Of Chest Tube Size, Shawn D St Peter, Krow Ampofo, Thomas Brogan, Michael D Cabana, Claudia Espinosa, Todd A Florin, Jeffrey S Gerber, Michelle Gill, Debra L Palazzi, Mark Sawyer, Angela Statile, Derek J Williams, Sheena Patel, Mark I Neuman, Samir S Shah

Faculty, Staff and Students Publications

This paper is part of a larger clinical practice guideline on the diagnosis and management of parapneumonic effusion and empyema in children, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations on the appropriate size of thoracostomy tube for drainage. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

Lifestyle Intervention Therapy Modulates Global Dna Methylation And Adipogenic Gene Expression In Severely Obese Hypogonadal Men, Siresha Bathina, Virginia Fuenmayor Lopez, Mia Prado, Salina Biene Teo, Dennis T Villareal, Rui Chen, Clifford Qualls, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Background/Objectives: Previous studies have suggested that lifestyle intervention (LSI) therapies involving diet and exercise can modulate DNA methylation; however, whether this occurs in severely obese hypogonadal men undergoing weight loss from diet and exercise remains unclear.

Methods: In this study, we investigated the effects of weight loss from diet and exercise on global DNA methylation as well as on the mRNA expression of specific demethylation enzymes, DNMT1, DNMT3A, and DNMT3B—in peripheral blood mononuclear cells (PBMCs) and DNA methylation markers in DNA of severely obese hypogonadal men. This is a secondary analysis of samples of severely obese (body …

Clinical Practice Guideline By The Infectious Diseases Society Of America And The Pediatric Infectious Diseases Society: 2026 Guideline Update On The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age, Shawn D St Peter, Krow Ampofo, Thomas Brogan, Michael D Cabana, Claudia Espinosa, Todd A Florin, Jeffrey S Gerber, Michelle Gill, Debra L Palazzi, Mark Sawyer, Angela M Statile, Derek J Williams, Sheena Patel, Mark I Neuman, Samir S Shah

Faculty, Staff and Students Publications

As the first part of an update to the clinical practice guideline on the management of community-acquired pneumonia in infants and children older than 3 months of age, we present six updated recommendations. The updated recommendations span the characterization and management of pneumonia with parapneumonic effusion. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

Label-Free Microfluidic Modulation Spectroscopy Monitors Rna Origami Structure And Stability, Phoebe S Tsoi, Lathan Lucas, Allan Chris M Ferreon, Ewan K S Mcrae, Josephine C Ferreon

Faculty, Staff and Students Publications

RNA origami enables genetically encoded, single-stranded RNA nanostructures that can self-assemble through co-transcriptional folding and are increasingly deployed as scaffolds for biosensing, synthetic biology, and nanomedicine. A recurring practical bottleneck is scalable, solution-phase readout of whether a designed scaffold has reached its intended base-paired architecture, whether it undergoes slow maturation or kinetic trapping, and how its stability is distributed across motifs. Here, we adapt microfluidic modulation spectroscopy (MMS) as a label-free structural biosensor for RNA folding by exploiting the rich 1760–1600 cm−1 vibrational fingerprints of RNA bases and base pairs. MMS alternates between sample and composition-matched buffer measurements in a …

2026 Clinical Practice Guideline Update By The Infectious Diseases Society Of America And The Pediatric Infectious Diseases Society On The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age: The Use Of Pleural Fluid Drainage Versus Observation, Shawn D St Peter, Krow Ampofo, Thomas Brogan, Michael D Cabana, Claudia Espinosa, Todd A Florin, Jeffrey S Gerber, Michelle Gill, Debra L Palazzi, Mark Sawyer, Angela M Statile, Derek J Williams, Sheena Patel, Mark I Neuman, Samir S Shah

Faculty, Staff and Students Publications

This paper is part of a larger clinical practice guideline on the diagnosis and management of parapneumonic effusion and empyema in children, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for pleural fluid drainage in children (3 months to 18 years) with parapneumonic effusion and empyema. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

2026 Clinical Practice Guideline Update By The Infectious Diseases Society Of America And The Pediatric Infectious Diseases Society On The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age: The Use Of Chest Ultrasound In Children With Parapneumonic Effusion, Shawn D St Peter, Krow Ampofo, Thomas Brogan, Michael D Cabana, Claudia Espinosa, Todd A Florin, Jeffrey S Gerber, Michelle Gill, Debra L Palazzi, Mark Sawyer, Angela M Statile, Derek J Williams, Sheena Patel, Samir S Shah, Mark I Neuman

Faculty, Staff and Students Publications

This paper is part of a larger clinical practice guideline on the diagnosis and management of parapneumonic effusion and empyema in children, developed by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. In this paper, the panel provides recommendations for the role of chest ultrasound to evaluate parapneumonic effusion and empyema. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

2026 Clinical Practice Guideline Update By The Infectious Diseases Society Of America And The Pediatric Infectious Diseases Society On The Management Of Community-Acquired Pneumonia In Infants And Children Older Than 3 Months Of Age: The Use Of Pleural Fluid Drainage Compared To Surgical Debridement, Shawn D St Peter, Krow Ampofo, Thomas Brogan, Michael D Cabana, Claudia Espinosa, Todd A Florin, Jeffrey S Gerber, Michelle Gill, Debra L Palazzi, Mark Sawyer, Angela M Statile, Derek J Williams, Sheena Patel, Samir S Shah, Mark I Neuman

Faculty, Staff and Students Publications

This paper is part of a larger clinical practice guideline on the diagnosis and management of parapneumonic effusion and empyema in children, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations on the choice of pleural fluid drainage by chest tube with fibrinolysis versus mechanical debridement. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

High Dietary Fiber Is Associated With Improved Outcomes In Patients With Melanoma And Sarcoma Treated With Immunotherapy Regardless Of Gut Microbiome Dysbiosis And Social Vulnerability, Brittany C Fields, Raymond S Traweek, Kai Jiang, Russell G Witt, Ashish Damania, Yi-Ju Chiang, Nadim Ajami, Elise Nassif-Haddad, Emily Z Keung, Manoj Chelvanambi, Xiaotao Zhang, Christine B Peterson, Jennifer A Wargo, Carrie R Daniel, Christina L Roland, Ashley M Holder

Faculty, Staff and Student Publications

Background: Social vulnerability, dietary fiber, and the gut microbiome have been individually implicated in clinical outcomes for melanoma and sarcoma patients. This study hypothesized that increasing social vulnerability is associated with insufficient dietary fiber intake and negatively associated with microbiome composition and clinical outcomes.

Methods: Clinicopathologic data, baseline fiber intake, and gut microbiome profiles were assessed in 153 patients with melanoma or sarcoma treated with immune checkpoint blockade (ICB) and prospectively followed. Patients' social vulnerability index (SVI) and fiber intake were evaluated for associations with microbiome composition, treatment response, and overall survival (OS).

Results: SVI percentile was 0.4 (interquartile ratio …

Radiation Doses To Cardiac Substructures Predict Elevation In High-Sensitivity Cardiac Troponin T Levels In Radiation Therapy For Lung Cancer, Xinru Chen, Xiaodong Zhang, Ting Xu, Radhe Mohan, Ruitao Lin, Mei Chen, Rachel C Maguire, Yao Zhao, Efstratios Koutroumpakis, Nicolas L Palaskas, Anita Deswal, Ali Ajdari, Joshua S Niedzielski, Sanjay S Shete, Laurence E Court, Jinzhong Yang, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: Cardiotoxicity is a major concern for patients undergoing thoracic radiation therapy. This study compared the predictive power of radiation dose-volume histogram (DVH) parameters and radiomic/dosiomic features of the whole heart (WH) and cardiac substructures for elevated circulating high-sensitivity cardiac troponin T (hs-cTnT), a biomarker for early detection of cardiac adverse events.

Methods and materials: A retrospective cohort of 160 patients with non-small cell lung cancer (NSCLC) from a completed prospective trial and a prospective cohort of 57 patients with NSCLC enrolled in an ongoing trial were analyzed. The endpoint was hs-cTnT elevation, indicated by an increase of ≥5 ng/L …

Misregulated Alternative Splicing In Endometriosis: A Role For Aberrant Mrna Variants In Endometriotic Cell Growth, Venkata Naga Goutham Davuluri, Michelle Dias, Roxanna Llinas, Kamath Neha, Pooja Popli, Shannon M Hawkins, Chandrakant Tayade, Elise T Courtois, Hari Krishna Yalamanchili, Ramakrishna Kommagani

Children’s Nutrition Research Center Staff Publications

Endometriosis is a chronic gynecological disorder marked by the growth of endometrial-like tissue outside the uterus, often leading to pelvic pain, inflammation, and infertility. Despite its global prevalence, diagnosis remains delayed, and effective non-surgical treatments are lacking. While recent transcriptomic studies have identified mRNA transcript changes in ectopic lesions, the contribution of alternative pre-mRNA splicing, a key posttranscriptional regulatory layer, remains largely unknown. In this study, we performed a comprehensive analysis of alternative splicing (AS) events in endometriotic lesions using transcriptomic data. We uncovered distinct alterations in alternative splicing events are associated with endometriosis, highlighting a previously underappreciated layer of …

Incidence Of Venous Thromboembolism In Women Receiving Transdermal Oestradiol/Testosterone With Micronised Progesterone In Accordance With Nice Guidelines, Amy Neville, Dan Reisel, John Benton, Mohit Khera, Louise Newson

Faculty, Staff and Students Publications

Background: Despite growing evidence supporting the long-term safety of hormone replacement therapy (HRT), concerns persist about certain adverse health outcomes, including venous thromboembolism (VTE). The aim of the study is to evaluate the risk of VTE in peri- and postmenopausal women treated with transdermal 17β-oestradiol with micronised progesterone or intrauterine progesterone (levonorgestrel) via the Mirena coil, in a real-world clinical setting.

Methods: The study included peri- and postmenopausal women attending a private menopause clinic between January 1, 2023, and December 31, 2023. Patients were actively undergoing treatment with transdermal oestradiol and progesterone in the form of micronised oral progesterone or …

Ccr7 Immune Cell Receptor Expression In Inflammatory Breast Cancer, Jennifer H Chen, Wintana Balema, Savitri Krishnamurthy, Alison N Lawrence, Natalie W Fowlkes, Richard A Larson, Surbhi Shivhare, Caren Sanchez, Megan M Rodriguez, Jangsoon Lee, Emilly S Villodre, Bisrat G Debeb, Naoto T Ueno, Steve Van Laere, Francois Bertucci, Hyunwoo Cho, Erik P Sulman, Bora Lim, Wendy A Woodward

Faculty, Staff and Student Publications

No abstract provided.

Pimicotinib Versus Placebo For Tenosynovial Giant Cell Tumour (Maneuver): An International, Randomised, Placebo-Controlled, Phase 3 Trial, Hairong Xu, Xiaohui Niu, Vinod Ravi, Javier Martin-Broto, Albiruni Abdul Razak, Ramy Saleh, Yong Zhou, Jingnan Shen, Tang Liu, Kamlesh Kumar Sankhala, César Serrano, Silvia Stacchiotti, Jing Wang, Giacomo G Baldi, Yi Feng, Yingqi Hua, Tao Li, Piotr Rutkowski, Xiaojing Zhang, Gabriel Tinoco, Qingping Zou, Boyao Shan, Xiangyu Zhu, Hans Gelderblom

Faculty, Staff and Student Publications

Background: Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive neoplasm that affects otherwise healthy adults. There are few systemic treatment options, highlighting an unmet need. We report the results of part 1 of the MANEUVER trial, which aimed to evaluate the efficacy and safety of pimicotinib, a highly selective, potent, colony-stimulating factor-1 receptor inhibitor, in patients with TGCT.

Methods: MANEUVER is a randomised, placebo-controlled, phase 3 study done in 40 specialised hospitals in Asia, Europe, and North America. Patients aged 18 years and older with unresectable, symptomatic TGCT (patient-reported worse stiffness or worst pain of at least 4 …

Gut Microbiota Modulation Via Repeated Donor Fecal Transplantation Improves Motor And Gastrointestinal Symptoms In Drug-Naïve Parkinson’S Disease: A Randomized Phase 2 Trial, Rui Zhang, Renyi Feng, Jiuqi Wang, Yongkang Chen, Han Liu, Qingyong Zhu, Haiyan Tian, Chi Qin, Junfang Teng, Beisha Tang, Min Wu, Jinsheng Zeng, Erxi Wu, Xuebing Ding, Xuejing Wang

Faculty, Staff and Students Publications

The gut-brain axis is increasingly recognized as a critical contributor to Parkinson's disease (PD) pathogenesis, yet the therapeutic impact of microbiota modulation remains unclear due to lack of clinical trials in drug-naïve patients. We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the safety, tolerability, and efficacy of repeated donor fecal microbiota transplantation (dFMT) in de novo PD. FMT was administered for seven days (200 mL on days 1-3; 50 mL on days 4-7) per 4-week cycle. Seventy-two patients were randomized 1:1 to receive dFMT or autologous FMT (aFMT), and 66 completed the trial. At 35 weeks, the …

The Efficacy And Safety Of Serratus Anterior Plane Block In Patients Undergoing Cardiac Surgery: A Systematic Review And Meta-Analysis, Xu-Bo Cui, Ming-Zhu Cui, Qiu-Ju Yang, Yang Liu, Meng-Qi Yi, Xiao-Yang Zhang, Yun-Tai Yao

Faculty, Staff and Student Publications

Background: Serratus anterior plane block (SAPB) is a widely used fascial block that reduces postoperative pain and perioperative opioid consumption. This meta-analysis assessed the efficacy and safety of SAPB in cardiac surgery patients.

Methods: We systematically searched PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang databases on May 10, 2024. Pooled relative risks and mean differences (MD) with 95% confidence intervals (CI) were calculated for dichotomous and continuous outcomes, respectively. Heterogeneity was assessed using the I2 statistic, and publication bias was evaluated using Egger test. Subgroup analyses were stratified by study design (randomized controlled trials …

Uncovering Hidden Prognostic Patterns In Colorectal Cancer Histology Using Unsupervised Learning: A Computational Pathology Study, Wen-Tong Zhou, Yong Liu, Gang Yu, Kuan-Song Wang, Chao Xu, Jonathan Greenbaum, Chong Wu, Lin-Dong Jiang, Christopher J Papasian, Hong-Mei Xiao, Hong-Wen Deng

Faculty, Staff and Student Publications

Colorectal cancer (CRC) remains a leading cause of cancer mortality globally, yet current histopathological diagnostics capture only limited features. This study aimed to discover subtle, prognostically significant histomorphological patterns in CRC tissues using unsupervised deep learning. We developed a framework integrating convolutional neural networks with deep clustering, trained on 23,341 image patches from 493 patients. We identified 30 distinct histomorphological clusters from CRC tissue images. Through univariate and multivariate survival analyses, three clusters (Cluster13, Cluster19, and Cluster24) were consistently associated with patient prognosis. These clusters were integrated with clinical factors (T stage, N stage, and differentiation degree) to construct a …

Telemedicine As A Gateway To Early-Phase Oncology Trials: Lessons From 14,000 Patients And Future Directions For Global Access And Equity, Carlos Torrado, Clark R Andersen, Lei Kang, Amanda L Brink, Taiwo Adesoye, Hung Le, Clover J Patterson, Anna Poullard, Jessica A Osburn, Harold N Tan, Mohamed A Gouda, Sheena Charles, Gabriele E Urschel, Tin-Yun Tang, David S Hong, Stephane Champiat, Aung Naing, Apostolia M Tsimberidou, Ecaterina E Dumbrava, Sarina A Piha-Paul, Jordi Rodon, Timothy A Yap, Paula R Pohlmann, Funda Meric-Bernstam, Siqing Fu

Faculty, Staff and Student Publications

Background: Telemedicine expanded rapidly during the COVID-19 pandemic, but its role in early-phase oncology trials remains uncertain. We evaluated its impact on recruitment, enrollment, equity, and access in a large phase I program.

Patients and methods: We retrospectively analyzed patients seen for first consultation in the MD Anderson Phase I Program (2016-2023). Recruitment (consent) and enrollment (treatment initiation) were compared by visit type, race/ethnicity, and geography across pre-pandemic (2016-2019), pandemic (2020-March 11, 2023), and post-public health emergency (PHE; March-December 2023) periods. A chart review of 400 patients validated findings.

Results: Of 14,085 patients, 7,247 were evaluated post-pandemic, with 36% (n …

Pan-Cancer Evolution Signatures Link Clonal Expansion To Dynamic Changes In The Tumor Immune Microenvironment, Xinyu Yang, Wei Liu, Geoff Macintyre, Peter Van Loo, Florian Markowetz, Peter Bailey, Ke Yuan

Faculty, Staff and Student Publications

Cancer is an evolutionary process characterized by profound intratumor heterogeneity (ITH), which can be quantified using in silico estimates of cancer cell fractions (CCFs) of tumor-specific somatic mutations. We demonstrate a data-driven approach based on CCF distributions to identify 4 robust pan-cancer evolutionary signatures from 4,146 tumors across 17 cancer types in The Cancer Genome Atlas (TCGA). These signatures define a continuum of cancer cell fractions reflecting neutral evolution, clonal expansion, and clonal fixation. Correlating evolutionary signatures with mutational and biological programs reveals that tumors enriched for clonal expansion and fixation are associated with immune evasion and distinct changes in …

In Vivo Hsc Gene Therapy Enables Sustained Ecd4-Ig Expression For Siv Prevention, Chang Li, Anna K Anderson, Anne-Sophie Kuhlmann, Veronica Nelson, Audrey Germond, Hongjie Wang, Aphrodite Georgakopoulou, Sucheol Gil, Jasmin Martinez-Reyes, Andrew Riker, Shruthi Shankar Raman, Jiho Kim, Philip Ng, Donna Palmer, Michael D Alpert, Nickolas Skamangas, Charles Bailey, Tianling Ou, Christine M Fennessey, Michael Farzan, Keith R Jerome, Brandon F Keele, Hans-Peter Kiem, André Lieber, John K Bui

Faculty, Staff and Students Publications

We aim to develop an in vivo hematopoietic stem cell (HSC) gene therapy approach for the prevention and control of HIV-1 infection. Toward this goal, we engineered helper-dependent adenovirus (HDAd) 6/3+ vectors to directly transduce HSCs in vivo, enabling progeny cells to secrete eCD4-Ig, a decoy protein that broadly neutralizes HIV/simian immunodeficiency virus (SIV) isolates by mimicking the primary viral receptor CD4 and coreceptors such as CCR5. In rhesus macaques, the HDAd 6/3+ platform achieved long-term expression of an enhanced eCD4-Ig variant (“eCD4-Ig-Emm06”) that retained potent neutralization efficacy in vivo. Transduced HSCs differentiated into lymphoid and myeloid lineages …