Digital Commons Network^™

Differentiation Between Descending Thoracic Aortic Diseases Using Machine Learning And Plasma Proteomic Signatures, Amanda Momenzadeh, Simion Kreimer, Dongchuan Guo, Matthew Ayres, Daniel Berman, Kuang-Yuh Chyu, Prediman K Shah, Dianna Milewicz, Ali Azizzadeh, Jesse G Meyer, Sarah Parker

Faculty, Staff and Student Publications

BACKGROUND: Descending thoracic aortic aneurysms and dissections can go undetected until severe and catastrophic, and few clinical indices exist to screen for aneurysms or predict risk of dissection.

METHODS: This study generated a plasma proteomic dataset from 75 patients with descending type B dissection (Type B) and 62 patients with descending thoracic aortic aneurysm (DTAA). Standard statistical approaches were compared to supervised machine learning (ML) algorithms to distinguish Type B from DTAA cases. Quantitatively similar proteins were clustered based on linkage distance from hierarchical clustering and ML models were trained with uncorrelated protein lists across various linkage distances with hyperparameter …

Real-World Multiple Myeloma Risk Factors And Outcomes By Non-Hispanic Black/African American And Non- Hispanic White Race/Ethnicity In The United States., Tondre Buck, Monique A Hartley-Brown, Yvonne A Efebera, Carter P Milner, Jeffrey A Zonder, Paul G Richardson, Taylor Salinardi, Megan S Rice

Oncology Articles

Examination of the impact of race and ethnicity on multiple myeloma (MM) outcomes has yielded inconsistent results. This retrospective, real-world (RW) study describes patient, disease, and treatment characteristics (and associations with survival outcomes) among newly diagnosed MM patients of non-Hispanic (NH) Black/African American (AA) and NH White race/ethnicity in the US. We included patients from the nationwide Flatiron Health electronic health record-derived de-identified database who initiated first line of therapy (LOT) for MM between January 1, 2016 and March 31, 2022. Of 4,614 patients in our study cohort, 23.3% were NH Black/AA. Non-Hispanic Black/AA patients were younger than NH White …

Differential Expression Of Wnt5a Long And Short Isoforms In Non-Muscle-Invasive Bladder Urothelial Carcinoma., Amy M Strope, Cody Phillips, Sabin Khadgi, Scott A Jenkinson, Karen T Coschigano, Ramiro Malgor

Oncology Articles

Wnt ligands belong to a family of secreted glycoproteins in which binding to a range of receptors/co-receptors activates several intracellular pathways. WNT5A, a member of the Wnt family, is classified as a non-canonical Wnt whose activation triggers planar cell polarity (PCP) and Ca+2 downstream pathways. Aberrant expression of WNT5A has been shown to play both protective and harmful roles in an array of conditions, such as inflammatory disease and cancer. In the present study, using histological, immunohistochemical, and molecular methods, we investigated the expression of two isoforms of WNT5A, WNT5A-Short (WNT5A-S) and WNT5A-Long (WNT5A-L) in bladder urothelial carcinoma (UC). Three …

Post Hoc Analysis Of Daratumumab Plus Lenalidomide, Bortezomib And Dexamethasone In Black Patients From Final Data Of The Griffin Study., Ajay K Nooka, Jonathan L Kaufman, Cesar Rodriguez, Andrzej Jakubowiak, Yvonne Efebera, Brandi Reeves, Tanya M Wildes, Sarah A Holstein, Larry D Anderson, Ashraf Badros, Leyla Shune, Ajai Chari, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Peter M Voorhees, Saad Z Usmani, Paul G Richardson

Oncology Articles

Due in part to racial disparities and underrepresentation in clinical studies, optimal therapies for Black patients with multiple myeloma remain undefined. This final analysis of GRIFFIN by race showed that the addition of daratumumab (D) to lenalidomide/bortezomib/dexamethasone (RVd) provides clinical benefit among both Black and White transplant-eligible newly diagnosed patients compared with RVd alone. However, Black patients were more likely to discontinue ≥1 drug due to treatment-emergent adverse events. In summary, these findings suggest a benefit of D-RVd front-line therapy among Black and White patients and underscore the importance of equitable treatment access for all patients.

Gender Differences In Risk Factor Profiles And Predictors Of Poor Outcomes Among Acute Stroke Patients: A Pilot Study From Egypt, Ahmed Abualhasan, Foad Abd-Allah, Sahar Salaheldin, Enas Alsayyad

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Stroke remains a leading cause of mortality and long-term disability worldwide, with significant socioeconomic implications. This study aimed to investigate gender-based differences in acute stroke patients regarding baseline characteristics, clinical presentation, and predictors of poor outcome Among Egyptian population.

Methods: We prospectively recruited 116 acute stroke patients admitted to the stroke unit at Cairo University Hospitals from January 2020 to June 2020. Detailed data on demographics, clinical characteristics, diagnostic workup, hospital course, and functional outcomes were collected. Poor outcome was defined as a modified Rankin Scale (mRS) ≥ 3 at discharge. Data were analyzed using SPSS version …

Insights Into The Influence Of Income Variability On Cardiovascular Risk In Non-Elderly Adults With Type 2 Diabetes, Ketrell Mcwhorter

UK CARES Faculty Publications

No abstract provided.

Limbic-Predominant Age-Related Tdp-43 Encephalopathy (Late-Nc): Co-Pathologies And Genetic Risk Factors Provide Clues About Pathogenesis, Peter T. Nelson, David Fardo, Xian Wu, Khine Zin Aung, Matthew D. Cykowski, Yuriko Katsumata

Neurology Faculty Publications

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is detectable at autopsy in more than one- third of people beyond age 85 years and is robustly associated with dementia independent of other pathologies. Although LATE-NC has a large impact on public health, there remain uncertainties about the underlying biologic mechanisms. Here, we review the literature from human studies that may shed light on pathogenetic mechanisms. It is increasingly clear that certain combinations of pathologic changes tend to coexist in aging brains. Although “pure” LATE-NC is not rare, LATE-NC often coexists in the same brains with Alzheimer disease neuropathologic change, brain arteriolosclerosis, …

Labrad : Vol 49, Issue 1 - June 2024, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• EDITORIAL
• ARTICLES
• Empowering Donors Through Technology
• Impact of Clinical Laboratories on Greenhouse gas emissions
• Embracing Digitalization and Sustainability: Streamlining Laboratory Reporting
• Accelerating Productivity and Performance: Transition from Transcribers to Working with Speech Recognition.
• ECO-Friendly Molecular Pathology Laboratory Practices
• Let’s Work to Build A Sustainable Histopathology Lab
• Laboratory Sustainability -Things to Promote Eco-Conscious Laboratory Environment
• A Guide to Develop the current and future Eco-Friendly Molecular Lab practices
• The Role of Microbiology Laboratories in Seaweed Reduction and Sustainable Agar Production
• The Role of Behavioral Change in Reducing Energy Use in Microbiology Laboratories
• Reducing Pathology’s Environmental Impact – What can we do?
• Water …

Polygenic Liability For Anxiety In Association With Comorbid Anxiety In Multiple Sclerosis, Kaarina Kowalec, Arvid Harder, Casandra Dolovich, Kathryn C Fitzgerald, Amber Salter, Yi Lu, Charles N Bernstein, James M Bolton, Gary Cutter, John D Fisk, Joel Gelernter, Lesley A Graff, Sara Hägg, Carol A Hitchon, Daniel F Levey, Fred D Lublin, Kyla A Mckay, Scott Patten, Amit Patki, Murray B Stein, Hemant K Tiwari, Jerry S Wolinsky, Ruth A Marrie

Faculty, Staff and Student Publications

OBJECTIVE: Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2-item scale polygenic score with anxiety in MS.

METHODS: Using a case-control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview-diagnosed, and lifetime self-report physician-diagnosed. The polygenic score was computed …

Radiogenomics-Based Risk Prediction Of Glioblastoma Multiforme With Clinical Relevance, Xiaohua Qian, Hua Tan, Xiaona Liu, Weiling Zhao, Michael D Chan, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Glioblastoma multiforme (GBM)is the most common and aggressive primary brain tumor. Although temozolomide (TMZ)-based radiochemotherapy improves overall GBM patients' survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudo-progression (PsP) is a treatment-related reaction with an increased contrast-enhancing lesion size at the tumor site or resection margins miming tumor recurrence on MRI. The accurate and reliable prognostication of GBM progression is urgently needed in the clinical management of GBM patients. Clinical data analysis indicates that the patients with PsP had superior overall and progression-free survival rates. In this study, we aimed …

A Case Of Charcot-Marie-Tooth Disease Type 2o (Cmt 20) Associated With Dync1h1 And Slc12a6 Mutations, Tehreem Arshad, Muhammad Jawad Hassan, Arsalan Ahmad

Pakistan Journal of Neurological Sciences (PJNS)

Charcot-Marie-Tooth disease (Charcot Marie-Tooth) comprises of a variety of hereditary diseases affecting the peripheral nervous system. Charcot Marie-Tooth2 is a subgroup caused by defects in the axon of the peripheral nerve cells. Charcot Marie-Tooth Type 2O is an uncommon type that affects less than one in a million people and is linked to specific genetic abnormalities. We report a case study of a 66-year-old individual with Charcot Marie-Tooth Type 2O, diagnosed on clinical presentation and identified through genetic analysis. Electromyography and nerve conduction studies supported the diagnosis of an axonal sensorineural neuropathy. A comprehensive genetic neuropathies panel led to the …

Best Practice Of Peritoneal Dialysis-Associated Gram-Negative Peritonitis In Children: Insights From The International Pediatric Peritoneal Dialysis Network Registry., Dagmara Borzych-Dużałka, Rebeca Same, Alicia Neu, Hui Kim Yap, Enrico Verrina, Sevcan A Bakkaloglu, Francisco Cano, Hiren Patel, Maria Szczepańska, Łukasz Obrycki, Ana Paula Spizzirri, Lisa Sartz, Karel Vondrak, Anabella Rebori, Gordana Milosevski-Lomic, Eugene Yu-Hin Chan, Biswanath Basu, Andrea Lazcano Pezo, Ariane Zaloszyc, Vimal Chadha, Franz Schaefer, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Gram-negative peritonitis (GNP) is associated with significant morbidity in children receiving long-term peritoneal dialysis (PD) and current treatment recommendations are based on limited data.

METHODS: Analysis of 379 GNP episodes in 308 children (median age 6.9 years, interquartile range [IQR]: 3.0-13.6) from 45 centers in 28 countries reported to the International Pediatric Peritoneal Dialysis Network registry between 2011 and 2023.

RESULTS: Overall, 74% of episodes responded well to empiric therapy and full functional recovery (FFR) was achieved in 82% of cases. In vitro bacterial susceptibility to empiric antibiotics and lack of severe abdominal pain at onset were associated with …

Once, I Was Very Very Scared And More: An Exploration Into Depictions Of Interpersonal Trauma In Children's Literature, Emma K. Siepmann

University Honors Theses

This thesis examines the ways in which experiences of interpersonal trauma are depicted in English-language contemporary literature for elementary-aged children (6-11 years). A review of academic literature suggests that interpersonal trauma can have devastating and ongoing repercussions for individuals and their communities, although establishing a sense of relational safety can help mitigate these effects and facilitate healing after a traumatic experience. This research explores age-appropriate literature as a therapeutic tool for developing relational safety and providing critical skills to children at risk for and recovering from interpersonal trauma. This study analyzes the depictions of interpersonal trauma found in 11 picture …

3d Bioprinting The Tumor Microenvironment For Immunotherapy Development, Molly Leyda, Tykeem Manor, John Szarejko, Douglas Myers, John M. Perry

Posters

The tumor microenvironment (TME) is a complex system that plays a crucial role in tumor progression, immune evasion, and therapy resistance. The TME is composed of various cell types, including tumor cells, stromal cells, and immune cells such as macrophages. Macrophages are versatile myeloid cells which can exhibit both pro-tumoral and anti-tumoral functions, depending on their phenotype and the TME context. M1 macrophages have demonstrated promising pro-inflammatory and anti-tumor effects, while tumor associated M2 macrophages (TAMs) play an anti-inflammatory role and promote tumor immune escape. Understanding the complex interactions between TAMs and the TME is, therefore, essential for developing effective …

Predictive Capacity Of Immune-Related Adverse Events And Cytokine Profiling In Neoadjuvant Immune Checkpoint Inhibitor Trials For Head And Neck Squamous Cell Carcinoma, Angela Alnemri, Sruti Tekumalla, Annie Moroco, Ioannis Vathiotis, Madalina Tuluc, Stacey Gargano, Tingting Zhan, David Cognetti, Joseph Curry, Athanassios Argiris, Alban Linnenbach, Andrew South, Larry Harshyne, Jennifer Johnson, Adam Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status.

METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival …

Rates Of Urinary Tract Infection In Transgender Women Postvaginoplasty Vs Cisgender Women: A Retrospective Cohort Study In A Large Us Health Network, David Gilbert, Aishwarya Gautam, Tomasz Tabernacki, Megan Mcnamara, Rachel Pope, Shubham Gupta, Kirtishri Mishra

Student Scholarship

Objective: To describe urinary tract infection (UTI) risk 3-month postvaginoplasty (VP) in transgender women (TW) compared to cis women (CW). Methods: Using TriNetX (TriNetX, Inc, Cambridge, MA), we built cohorts of 2041 TW and 48,374,745 CW. Outcomes were ≥1 instance of UTI or Cystitis, and assessed from 3-6, 3-12, 3-36 months, and 3 months-10 years post-VP. TW and CW were age-cohorted (18-39, 40-59, 60-74) and compared at each time interval. Kaplan-Meier was used to account for loss to follow-up, along with hazard ratios and log-rank tests to determine significance (P <.05). Results: For all time intervals and age ranges, TW had a significantly (P <.0001-P = .0088) higher probability of developing a UTI compared to CW. The largest difference was ages 40-59 ten-year post-VP. In this analysis, CW and TW had a 12.96% and 29.34% cumulative outcome incidence, respectively. Cox proportional hazard analysis demonstrated increased hazard for TW compared to CW. Hazard ratios between CW and TW ranged from 1.363 (ages 18-39 at 10 years, 95%CI: 1.119,1.660) to 3.522 (ages 60-74 at 12 months, 95%CI: 1.951,6.360). Conclusion: We found a significantly higher probability of TW developing UTIs compared to age-cohorted CW. Contributing factors may include difficulties with neovaginal perineal hygiene, lack of commensal bacteria and vaginal mucosa, larger urethral meatus, high rates of meatal stenosis, and nonnative bacteria introduced through dilators and douching. These findings may help improve quality of postoperative care in TW.

Evaluation Of Aluminum Exposure In Neonates Receiving Parenteral Nutrition, Emma Sedarski

2024 Swedish Learning and Celebration Day

No abstract provided.

From Pre-Clinical To Translational Brain Metastasis Research: Current Challenges And Emerging Opportunities, Emilija Aleksandrovic, Siyuan Zhang, Dihua Yu

Faculty, Staff and Student Publications

Brain metastasis, characterized by poor clinical outcomes, is a devastating disease. Despite significant mechanistic and therapeutic advances in recent years, pivotal improvements in clinical interventions have remained elusive. The heterogeneous nature of the primary tumor of origin, complications in drug delivery across the blood-brain barrier, and the distinct microenvironment collectively pose formidable clinical challenges in developing new treatments for patients with brain metastasis. Although current preclinical models have deepened our basic understanding of the disease, much of the existing research on brain metastasis has employed a reductionist approach. This approach, which often relies on either in vitro systems or in …

Genetic Evidence For Functional Diversification Of Gram-Negative Intermembrane Phospholipid Transporters, Ashutosh K Rai, Katsuhiro Sawasato, Haley C Bennett, Anastasiia Kozlova, Genevieve C Sparagna, Mikhail Bogdanov, Angela M Mitchell

Faculty, Staff and Student Publications

The outer membrane of gram-negative bacteria is a barrier to chemical and physical stress. Phospholipid transport between the inner and outer membranes has been an area of intense investigation and, in E. coli K-12, it has recently been shown to be mediated by YhdP, TamB, and YdbH, which are suggested to provide hydrophobic channels for phospholipid diffusion, with YhdP and TamB playing the major roles. However, YhdP and TamB have different phenotypes suggesting distinct functions. It remains unclear whether these functions are related to phospholipid metabolism. We investigated a synthetic cold sensitivity caused by deletion of fadR, a transcriptional regulator …

Associations Between Longer Leukocyte Telomere Length And Increased Lung Cancer Risk Among Never Smokers In Urban China, Jason Y Y Wong, Xiao-Ou Shu, Wei Hu, Batel Blechter, Jianxin Shi, Kevin Wang, Richard Cawthon, Qiuyin Cai, Gong Yang, Mohammad L Rahman, Bu-Tian Ji, Yutang Gao, Wei Zheng, Nathaniel Rothman, Qing Lan

Faculty, Staff and Student Publications

BACKGROUND: The complex relationship between measured leukocyte telomere length (LTL), genetically predicted LTL (gTL), and carcinogenesis is exemplified by lung cancer. We previously reported associations between longer pre-diagnostic LTL, gTL, and increased lung cancer risk among European and East Asian populations. However, we had limited statistical power to examine the associations among never smokers by gender and histology.

METHODS: To investigate further, we conducted nested case-control analyses on an expanded sample of never smokers from the prospective Shanghai Women's Health Studies (798 cases and 792 controls) and Shanghai Men's Health Studies (161 cases and 162 controls). We broke the case-control …

A Prismatic View Of The Epigenetic-Metabolic Regulatory Axis In Breast Cancer Therapy Resistance, Chandrima Das, Apoorva Bhattacharya, Swagata Adhikari, Atanu Mondal, Payel Mondal, Santanu Adhikary, Siddhartha Roy, Kenneth Ramos, Kamlesh K Yadav, John A Tainer, Tej K Pandita

Faculty, Staff and Student Publications

Epigenetic regulation established during development to maintain patterns of transcriptional expression and silencing for metabolism and other fundamental cell processes can be reprogrammed in cancer, providing a molecular mechanism for persistent alterations in phenotype. Metabolic deregulation and reprogramming are thus an emerging hallmark of cancer with opportunities for molecular classification as a critical preliminary step for precision therapeutic intervention. Yet, acquisition of therapy resistance against most conventional treatment regimens coupled with tumor relapse, continue to pose unsolved problems for precision healthcare, as exemplified in breast cancer where existing data informs both cancer genotype and phenotype. Furthermore, epigenetic reprograming of the …

Mash: Mediation Analysis Of Survival Outcome And High-Dimensional Omics Mediators With Application To Complex Diseases, Sunyi Chi, Christopher R Flowers, Ziyi Li, Xuelin Huang, Peng Wei

Faculty, Staff and Student Publications

Environmental exposures such as cigarette smoking influence health outcomes through intermediate molecular phenotypes, such as the methylome, transcriptome, and metabolome. Mediation analysis is a useful tool for investigating the role of potentially high-dimensional intermediate phenotypes in the relationship between environmental exposures and health outcomes. However, little work has been done on mediation analysis when the mediators are high-dimensional and the outcome is a survival endpoint, and none of it has provided a robust measure of total mediation effect. To this end, we propose an estimation procedure for Mediation Analysis of Survival outcome and High-dimensional omics mediators (MASH) based on sure …

International Consensus Guidelines For The Definition, Detection, And Interpretation Of Autophagy-Dependent Ferroptosis, Xin Chen, Andrey S Tsvetkov, Han-Ming Shen, Ciro Isidoro, Nicholas T Ktistakis, Andreas Linkermann, Werner J H Koopman, Hans-Uwe Simon, Lorenzo Galluzzi, Shouqing Luo, Daqian Xu, Wei Gu, Olivier Peulen, Qian Cai, David C Rubinsztein, Jen-Tsan Chi, Donna D Zhang, Changfeng Li, Shinya Toyokuni, Jinbao Liu, Jong-Lyel Roh, Enyong Dai, Gabor Juhasz, Wei Liu, Jianhua Zhang, Minghua Yang, Jiao Liu, Ling-Qiang Zhu, Weiping Zou, Mauro Piacentini, Wen-Xing Ding, Zhenyu Yue, Yangchun Xie, Morten Petersen, David A Gewirtz, Michael A Mandell, Charleen T Chu, Debasish Sinha, Eftekhar Eftekharpour, Boris Zhivotovsky, Sébastien Besteiro, Dmitry I Gabrilovich, Do-Hyung Kim, Valerian E Kagan, Hülya Bayir, Guang-Chao Chen, Scott Ayton, Jan D Lünemann, Masaaki Komatsu, Stefan Krautwald, Ben Loos, Eric H Baehrecke, Jiayi Wang, Jon D Lane, Junichi Sadoshima, Wan Seok Yang, Minghui Gao, Christian Münz, Michael Thumm, Martin Kampmann, Di Yu, Marta M Lipinski, Jace W Jones, Xuejun Jiang, Herbert J Zeh, Rui Kang, Daniel J Klionsky, Guido Kroemer, Daolin Tang

Faculty, Staff and Student Publications

Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or executing ferroptotic cell death through the selective degradation of anti-injury proteins or organelles. Conversely, other forms of selective autophagy (e.g. reticulophagy and lysophagy) enhance the cellular defense …

The Combination Of Tumor Mutational Burden And T-Cell Receptor Repertoire Predicts The Response To Immunotherapy In Patients With Advanced Non-Small Cell Lung Cancer, Yalun Li, Liyan Ji, Yingqian Zhang, Jiexin Zhang, Alexandre Reuben, Hao Zeng, Qin Huang, Qi Wei, Sihan Tan, Xuefeng Xia, Weimin Li, Jianjun Zhang, Panwen Tian

Faculty, Staff and Student Publications

Tumor mutational burden (TMB) and T-cell receptor (TCR) might predict the response to immunotherapy in patients with non-small cell lung cancer (NSCLC). However, the predictive value of the combination of TMB and TCR was not clear. Targeted DNA and TCR sequencing were performed on tumor biopsy specimens. We combined TMB and TCR diversity into a TMB-and-TCR (TMR) score using logistic regression. In total, 38 patients with advanced NSCLC were divided into a discovery set (

Prioritization Of Kidney Cell Types Highlights Myofibroblast Cells In Regulating Human Blood Pressure, Mahboube Ganji-Arjenaki, Zoha Kamali, International Consortium Of Blood Pressure; Soroush Sardari, Soroush Sardari, Martin De Borst, Harold Snieder, Ahmad Vaez

Faculty, Staff and Student Publications

INTRODUCTION: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP.

METHODS: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years.

RESULTS: …

Kcnk1 Promotes Proliferation And Metastasis Of Breast Cancer Cells By Activating Lactate Dehydrogenase A (Ldha) And Up-Regulating H3k18 Lactylation, Xiangchan Hou, Jiawei Ouyang, Le Tang, Pan Wu, Xiangying Deng, Qijia Yan, Lei Shi, Songqing Fan, Chunmei Fan, Can Guo, Qianjin Liao, Yong Li, Wei Xiong, Guiyuan Li, Zhaoyang Zeng, Fuyan Wang

Faculty, Staff and Students Publications

Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in …

Multidisciplinary Training In Dermatology: Exploring The Spectrum Of Board Certifications Among Physicians Practicing Dermatology In Texas, Rebecca H Lee, Jason Lee, Jonny Hatch, Lilian Zhan, Braden Van Alfen, Mark Conley, Tracy Zhao, Carlos Gomez-Meade

Faculty, Staff and Students Publications

Dermatology, a medical specialty focused on skin, hair, and nail conditions, often overlaps with various medical specialties. Although most physicians practicing dermatology are board-certified in dermatology, there are physicians practicing dermatology who are board-certified in a variety of different medical specialties. This cross-sectional study examines the board certifications of physicians who reported practicing dermatology in Texas. Data were sourced from the Texas Medical Board database updated in August 2023. The data showed that out of 1,614 practicing physicians declaring dermatology as a specialty in Texas, 1,080 (66.91%) physicians had one board certification, 200 (12.39%) had two, and 15 (0.93%) had …

Bacillary Angiomatosis In A Patient With Hiv And Disseminated Mycobacterium Avium Complex Infection, Ibeth P Caceres, Angelique Ruml, Rubi Montejano, Omid Jalali, Theodore Rosen

Faculty, Staff and Students Publications

Bartonella is a genus of arthropod-borne bacterial pathogens that typically cause persistent infections of erythrocytes and endothelial cells in mammalian hosts. The species that primarily infect humans are Bartonella henselae and Bartonella quintana. Depending on immune status, the clinical presentation of B. henselae may differ, manifesting as cat-scratch disease in immunocompetent individuals or bacillary angiomatosis (BA) and peliosis in immunocompromised patients. The cutaneous manifestations of BA are typically characterized by occasionally painful, angiomatous papules and nodules, often with a chronic, persistent course. Herein, we present a case of biopsy-confirmed B. henselae infection in a 32-year-old HIV-positive female with acquired immunodeficiency …

Autologous Her2-Specific Car T Cells After Lymphodepletion For Advanced Sarcoma: A Phase 1 Trial, Meenakshi Hegde, Shoba Navai, Christopher Derenzo, Sujith K Joseph, Khaled Sanber, Mengfen Wu, Ahmed Z Gad, Katherine A Janeway, Matthew Campbell, Dolores Mullikin, Zeid Nawas, Catherine Robertson, Pretty R Mathew, Huimin Zhang, Birju Mehta, Raksha R Bhat, Angela Major, Ankita Shree, Claudia Gerken, Mamta Kalra, Rikhia Chakraborty, Sachin G Thakkar, Olga Dakhova, Vita S Salsman, Bambi Grilley, Natalia Lapteva, Adrian Gee, Gianpietro Dotti, Riyue Bao, Ahmed Hamed Salem, Tao Wang, Malcolm K Brenner, Helen E Heslop, Winfried S Wels, M John Hicks, Stephen Gottschalk, Nabil Ahmed

Faculty, Staff and Students Publications

In this prospective, interventional phase I study (NCT00902044) for patients with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T-cells (HER2-CART) after lymphodepletion with cyclophosphamide (Cy) +/− fludarabine (Flu): 1×108 T-cells/m2 after Flu (cohort A) or Flu/Cy (cohort B), and 1×108 CAR-positive T-cells/m2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2-CART after lymphodepletion. The determination of antitumor responses was the secondary outcome. Thirteen patients were treated in 14 enrollments with 7 receiving multiple infusions. HER2-CART expanded after 19 of 21 infusions. Nine of 12 patients in cohorts A and …

Improving Access To Exome Sequencing In A Medically Underserved Population Through The Texome Project, Blake Vuocolo, Ryan J German, Seema R Lalani, Chaya N Murali, Carlos A Bacino, Stephanie Baskin, Rebecca Littlejohn, John D Odom, Scott Mclean, Carrie Schmid, Morgan Nutter, Melissa Stuebben, Emily Magness, Olivia Juarez, Dina El Achi, Bailey Mitchell, Kevin E Glinton, Laurie Robak, Sandesh C S Nagamani, Lisa Saba, Adasia Ritenour, Lilei Zhang, Haley Streff, Katie Chan, K Jordan Kemere, Kent Carter, Texome Project, Nichole Owen, Liesbeth Vossaert, Pengfei Liu, Hugo Bellen, Michael F Wangler

Faculty, Staff and Students Publications

PURPOSE: Genomic medicine can end diagnostic odysseys for patients with complex phenotypes; however, limitations in insurance coverage and other systemic barriers preclude individuals from accessing comprehensive genetics evaluation and testing.

METHODS: The Texome Project is a 4-year study that reduces barriers to genomic testing for individuals from underserved and underrepresented populations. Participants with undiagnosed, rare diseases who have financial barriers to obtaining exome sequencing (ES) clinically are enrolled in the Texome Project.

RESULTS: We highlight the Texome Project process and describe the outcomes of the first 60 ES results for study participants. Participants received a genetic evaluation, ES, and return …