Digital Commons Network^™

Protein Profiling By Reverse Phase Protein Array (Rppa) In Classical Hairy Cell Leukemia (Hcl) And Hcl-Variant, Fieke W Hoff, Ti'ara L Griffen, Yihua Qiu, Steven M Kornblau

Faculty, Staff and Student Publications

Classical hairy cell leukemia (HCL-c) and HCL variant (HCL-v) are recognized as separate entities with HCL-v having significantly shorter overall survival. Proteomic studies, shown to be prognostic in various forms of leukemia, have not been performed in HCL. We performed reverse phase protein array-based protein profiling with 384 antibodies in HCL-c (

Contemporary Outcomes In Idh-Mutated Acute Myeloid Leukemia: The Impact Of Co-Occurring Npm1 Mutations And Venetoclax-Based Treatment, Curtis A Lachowiez, Patrick K Reville, Hagop Kantarjian, Elias Jabbour, Gautam Borthakur, Naval Daver, Ghayas Issa, Ken Furudate, Tomoyuki Tanaka, Sherry Pierce, Guilin Tang, Keyur P Patel, Jeffrey Medeiros, Hussein A Abbas, Fadi Haddad, Daniel Hammond, Nicholas J Short, Abhishek Maiti, Musa Yilmaz, Koji Sasaki, Koichi Takahashi, Naveen Pemmaraju, Marina Konopleva, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M Kadia, Sanam Loghavi, Courtney D Dinardo

Faculty, Staff and Student Publications

Isocitrate dehydrogenase 1 or 2 (IDH1 or IDH2) mutations occur frequently in newly diagnosed (ND) acute myeloid leukemia (AML) often with co-occurring NPM1 mutations, which may influence treatment outcomes. Detailed analysis of IDH-mutated AML treated with venetoclax and influence of co-occurring NPM1 mutations remains unclear. This retrospective single-center cohort study evaluated clinical and molecular demographics,response and survival, and impact of co-occurring NPM1 mutations in patients with IDH1 or IDH2-mutated AML. 556 patients with IDH1, IDH2, and/or NPM1 mutated AML were included. Patients with IDH1mut AML (N = 119) were more likely to have older age, sAML, ELN-adverse risk disease, and …

Advances In Understanding Cancer-Associated Neurogenesis And Its Implications On The Neuroimmune Axis In Cancer, Ismail Yaman, Didem Ağaç Çobanoğlu, Tongxin Xie, Yi Ye, Moran Amit

Faculty, Staff and Student Publications

Nerves and immunologic mediators play pivotal roles in body homeostasis by interacting with each other through diverse mechanisms. The spread of nerves in the tumor microenvironment increases tumor cell proliferation and disease progression, and this correlates with poor patient outcomes. The effects of sympathetic and parasympathetic nerves on cancer regulation are being investigated. Recent findings demonstrate the possibility of developing therapeutic strategies that target the tumor microenvironment and its components such as immune cells, neurotransmitters, and extracellular vesicles. Therefore, examining and understanding the mechanisms and pathways associated with the sympathetic and parasympathetic nervous systems, neurotransmitters, cancer-derived mediators and their interactions …

The Impact Of Covid-19 On Patients With Ibd In A Prospective European Cohort Study, Rana O Afifi

Faculty, Staff and Student Publications

No abstract provided.

Acute Depletion Of Human Core Nucleoporin Reveals Direct Roles In Transcription Control But Dispensability For 3d Genome Organization, Xiaoyu Zhu, Chuangye Qi, Ruoyu Wang, Joo-Hyung Lee, Jiaofang Shao, Lanxin Bei, Feng Xiong, Phuoc T Nguyen, Guojie Li, Joanna Krakowiak, Su-Pin Koh, Lukas M Simon, Leng Han, Travis I Moore, Wenbo Li

Faculty, Staff and Student Publications

The nuclear pore complex (NPC) comprises more than 30 nucleoporins (NUPs) and is a hallmark of eukaryotes. NUPs have been suggested to be important in regulating gene transcription and 3D genome organization. However, evidence in support of their direct roles remains limited. Here, by Cut&Run, we find that core NUPs display broad but also cell-type-specific association with active promoters and enhancers in human cells. Auxin-mediated rapid depletion of two NUPs demonstrates that NUP93, but not NUP35, directly and specifically controls gene transcription. NUP93 directly activates genes with high levels of RNA polymerase II loading and transcriptional elongation by facilitating full …

Global Changes In Chromatin Accessibility And Transcription In Growth Hormone-Secreting Pituitary Adenoma, Meng Wang, Chenxing Ji, Yichao Zhang, Zhiqiang Zhang, Yu Zhang, Huiping Guo, Nidan Qiao, Xiang Zhou, Xiaoyun Cao, Zhen Ye, Yifei Yu, Vladimir Melnikov, Wei Gong, Min He, Zhaoyun Zhang, Yao Zhao, Xuelong Wang, Gang Wei, Zhao Ye

Faculty, Staff and Student Publications

PURPOSE: Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of growth hormone and insulin-like growth factor 1, causing increased morbidity and mortality. Previous studies have investigated the transcription of GHPA. However, the gene regulatory landscape has not been fully characterized. The objective of our study was to unravel the changes in chromatin accessibility and transcription in GHPA.

METHODS: Six patients diagnosed with GHPA in the Department of Neurosurgery at Huashan Hospital were enrolled in our study. Primary pituitary adenoma tissues and adjacent normal pituitary specimens with no morphologic abnormalities from these six patients were obtained at …

Mucins Muc5ac And Muc5b Are Variably Packaged In The Same And In Separate Secretory Granules, Oanh N Hoang, Anna Ermund, Ana M Jaramillo, Dalia Fakih, Cory B French, Jose R Flores, Harry Karmouty-Quintana, Jesper M Magnusson, Giorgio Fois, Michael Fauler, Manfred Frick, Peter Braubach, Joshua B Hales, Richard C Kurten, Reynold Panettieri, Leoncio Vergara, Camille Ehre, Roberto Adachi, Michael J Tuvim, Gunnar C Hansson, Burton F Dickey

Faculty, Staff and Student Publications

No abstract provided.

Acute Depletion Of Human Core Nucleoporin Reveals Direct Roles In Transcription Control But Dispensability For 3d Genome Organization, Xiaoyu Zhu, Chuangye Qi, Ruoyu Wang, Joo-Hyung Lee, Jiaofang Shao, Lanxin Bei, Feng Xiong, Phuoc T Nguyen, Guojie Li, Joanna Krakowiak, Su-Pin Koh, Lukas M Simon, Leng Han, Travis I Moore, Wenbo Li

Faculty, Staff and Student Publications

The nuclear pore complex (NPC) comprises more than 30 nucleoporins (NUPs) and is a hallmark of eukaryotes. NUPs have been suggested to be important in regulating gene transcription and 3D genome organization. However, evidence in support of their direct roles remains limited. Here, by Cut&Run, we find that core NUPs display broad but also cell-type-specific association with active promoters and enhancers in human cells. Auxin-mediated rapid depletion of two NUPs demonstrates that NUP93, but not NUP35, directly and specifically controls gene transcription. NUP93 directly activates genes with high levels of RNA polymerase II loading and transcriptional elongation by facilitating full …

The Breast Cancer Microenvironment And Lipoprotein Lipase: Another Negative Notch For A Beneficial Enzyme?, Zhu-Hong Chen, Yu-Ling Cui, Jing-Ting Sun, Yu-Ting Li, Chi Zhang, Yang-Ming Zhang, Ze-Yang Li, Yu-Xuan Shang, Min-Hua Ni, Bo Hu, Lin-Feng Yan, Wen Wang

Faculty, Staff and Student Publications

Objectives: To quantitatively summarize the specific changes in brain structure and function in migraine patients.

Methods: A literature screening of migraine was conducted from inception to Sept 1, 2022, in PubMed, Web of Science, Cochrane Library, and Medline databases using the keyword combination of "migraine and MRI." Activation likelihood estimation (ALE) was performed to assess the differentiation of functional connectivity (FC), regional homogeneity (ReHo), and gray matter volume (GMV) of migraine patients.

Results: Eleven voxel-based morphometry (VBM) studies and 25 resting-state fMRI (rs-fMRI) studies (16 FC and 9 ReHo studies) were included in this study. ALE analysis revealed the ReHo …

Is Loss Of P53 A Driver Of Ductal Carcinoma In Situ Progression?, Rhiannon L Morrissey, Alastair M Thompson, Guillermina Lozano

Faculty, Staff and Student Publications

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive carcinoma. Multiple studies have shown that DCIS lesions typically possess a driver mutation associated with cancer development. Mutation in the TP53 tumour suppressor gene is present in 15-30% of pure DCIS lesions and in ~30% of invasive breast cancers. Mutations in TP53 are significantly associated with high-grade DCIS, the most likely form of DCIS to progress to invasive carcinoma. In this review, we summarise published evidence on the prevalence of mutant TP53 in DCIS (including all DCIS subtypes), discuss the availability of mouse models for the study of DCIS …

Rad Regulation Of Cav12 Channels Controls Cardiac Fight-Or-Flight Response, Arianne Papa, Sergey I Zakharov, Alexander N Katchman, Jared S Kushner, Bi-Xing Chen, Lin Yang, Guoxia Liu, Alejandro Sanchez Jimenez, Robyn J Eisert, Gary A Bradshaw, Wen Dun, Shah R Ali, Aaron Rodriques, Karen Zhou, Veli Topkara, Mu Yang, John P Morrow, Emily J Tsai, Arthur Karlin, Elaine Wan, Marian Kalocsay, Geoffrey S Pitt, Henry M Colecraft, Manu Ben-Johny, Steven O Marx

Faculty, Staff and Student Publications

Fight-or-flight responses involve β-adrenergic-induced increases in heart rate and contractile force. In the present study, we uncover the primary mechanism underlying the heart's innate contractile reserve. We show that four protein kinase A (PKA)-phosphorylated residues in Rad, a calcium channel inhibitor, are crucial for controlling basal calcium current and essential for β-adrenergic augmentation of calcium influx in cardiomyocytes. Even with intact PKA signaling to other proteins modulating calcium handling, preventing adrenergic activation of calcium channels in Rad-phosphosite-mutant mice (4SA-Rad) has profound physiological effects: reduced heart rate with increased pauses, reduced basal contractility, near-complete attenuation of β-adrenergic contractile response and diminished …

Prognostic Significance Of Preoperative And Postoperative Ca 19–9 Normalization In Pancreatic Adenocarcinoma Treated With Neoadjuvant Therapy Or Surgery First, Timothy P Diperi, Timothy E Newhook, Laura R Prakash, Naruhiko Ikoma, Jessica E Maxwell, Michael P Kim, Jeffrey E Lee, Matthew H G Katz, Ching-Wei D Tzeng

Faculty, Staff and Student Publications

BACKGROUND: Normal(ization) of serum carbohydrate 19-9 (CA19-9) before/after surgery has not been compared in patients with pancreatic adenocarcinoma (PDAC) treated with neoadjuvant therapy (NT) versus surgery-first (SF).

METHODS: Characteristics for patients with PDAC who underwent resection from July 2011 to October 2018 were collected. Patients with pre-/postoperative CA19-9, bilirubin/dL, and initial CA19-9 > 1 U/ml were included. Overall survival (OS) and recurrence-free survival (RFS) were compared by pre-/postoperative CA19-9.

RESULTS: In patients receiving NT, normal pre/postoperative CA19-9 ("NT

CONCLUSIONS: While a normal(ized) postoperative CA19-9 may result in similar survival as preoperative normal(ization), postoperative normalization failed to occur in nearly 30% of …

An Optimized Bioassay For Screening Combined Anticoronaviral Compounds For Efficacy Against Feline Infectious Peritonitis Virus With Pharmacokinetic Analyses Of Gs-441524, Remdesivir, And Molnupiravir In Cats, Sarah Cook, Luke Wittenburg, Victoria C Yan, Jacob H Theil, Diego Castillo, Krystle L Reagan, Sonyia Williams, Cong-Dat Pham, Chun Li, Florian L Muller, Brian G Murphy

Faculty, Staff and Student Publications

Feline infectious peritonitis (FIP) is a fatal disease of cats that currently lacks licensed and affordable vaccines or antiviral therapeutics. The disease has a spectrum of clinical presentations including an effusive ("wet") form and non-effusive ("dry") form, both of which may be complicated by neurologic or ocular involvement. The feline coronavirus (FCoV) biotype, termed feline infectious peritonitis virus (FIPV), is the etiologic agent of FIP. The objective of this study was to determine and compare the in vitro antiviral efficacies of the viral protease inhibitors GC376 and nirmatrelvir and the nucleoside analogs remdesivir (RDV), GS-441524, molnupiravir (MPV; EIDD-2801), and β-D-N

Acetyl-Coenzyme A Synthetase 2 Potentiates Macropinocytosis And Muscle Wasting Through Metabolic Reprogramming In Pancreatic Cancer, Zhijun Zhou, Yu Ren, Jingxuan Yang, Mingyang Liu, Xiuhui Shi, Wenyi Luo, Kar-Ming Fung, Chao Xu, Michael S Bronze, Yuqing Zhang, Courtney W Houchen, Min Li

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Rapid deconditioning, also called cachexia, and metabolic reprogramming are two hallmarks of pancreatic cancer. Acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is an acetyl-enzyme A synthetase that contributes to lipid synthesis and epigenetic reprogramming. However, the role of ACSS2 on the nonselective macropinocytosis and cancer cachexia in pancreatic cancer remains elusive. In this study, we demonstrate that ACSS2 potentiates macropinocytosis and muscle wasting through metabolic reprogramming in pancreatic cancer.

METHODS: Clinical significance of ACSS2 was analyzed using samples from patients with pancreatic cancer. ACSS2-knockout cells were established using the clustered regularly interspaced short palindromic repeats-associated protein …

Exploiting Dna Replication Stress As A Therapeutic Strategy For Breast Cancer, Jing Zhang, Doug W Chan, Shiaw-Yih Lin

Faculty, Staff and Student Publications

Proliferating cells rely on DNA replication to ensure accurate genome duplication. Cancer cells, including breast cancer cells, exhibit elevated replication stress (RS) due to the uncontrolled oncogenic activation, loss of key tumor suppressors, and defects in the DNA repair machinery. This intrinsic vulnerability provides a great opportunity for therapeutic exploitation. An increasing number of drug candidates targeting RS in breast cancer are demonstrating promising efficacy in preclinical and early clinical trials. However, unresolved challenges lie in balancing the toxicity of these drugs while maintaining clinical efficacy. Furthermore, biomarkers of RS are urgently required to guide patient selection. In this review, …

Latent Classes Of Bidirectional Face-To-Face And Cyber Intimate Partner Violence Among Lesbian, Gay, And Bisexual Emerging Adults: The Role Of Minority Stressors, Roman Ronzón-Tirado, Ruby Charak, Ines Cano-Gonzalez, Sidsel Karsberg, Phillip W. Schnarrs

Psychological Science Faculty Publications

The rates of intimate partner violence have been found to be higher among lesbian, gay, and bisexual (LGB) individuals when compared with heterosexual populations. However, lesser is known about the impact of specific minority stressors experienced by LGB populations on their face-to-face intimate partner violence (IPV) and cyber IPV experiences. Using a three-step latent class approach, the present study investigated (i) the latent classes of self-reported types of face-to-face IPV and cyber IPV perpetration and victimization and (ii) their associations with LGB distal and proximal minority stressors (i.e., vicarious trauma, discrimination, family rejection, and LGB-identity disclosure). Participants were 288 LGB …

Why Post- Leaving Certificate Students In Ireland From Disadvantaged Backgrounds Are Less Likely To Proceed To Third-Level Education, Edward Hayes

Theses

Educational disadvantage continues to be a cause for concern, and addressing it remains at the forefront of education policy in Ireland (Houses of Oireachtas, 2019; Weir et al., 2017). This research extended across the academic years 2019-2020 and 2020-2021 and during the period of the global COVID-19 pandemic, which imposed public health measures, and enforced an emergency online digital learning environment. A socio-economic profile of Ireland’s student body registered an attainment gap between rich and poor, finding that young people from backgrounds of disadvantage continue to be underrepresented at third-level when compared to their middle-class counterparts (HEA, 2020). The primary …

A Blood-Based Metabolite Panel For Distinguishing Ovarian Cancer From Benign Pelvic Masses, Ehsan Irajizad, Chae Y Han, Joseph Celestino, Ranran Wu, Eunice Murage, Rachelle Spencer, Jennifer B Dennison, Jody Vykoukal, James P Long, Kim Anh Do, Charles Drescher, Karen Lu, Zhen Lu, Robert C Bast, Sam Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

PURPOSE: To assess the contributions of circulating metabolites for improving upon the performance of the risk of ovarian malignancy algorithm (ROMA) for risk prediction of ovarian cancer among women with ovarian cysts.

EXPERIMENTAL DESIGN: Metabolomic profiling was performed on an initial set of sera from 101 serous and nonserous ovarian cancer cases and 134 individuals with benign pelvic masses (BPM). Using a deep learning model, a panel consisting of seven cancer-related metabolites [diacetylspermine, diacetylspermidine, N-(3-acetamidopropyl)pyrrolidin-2-one, N-acetylneuraminate, N-acetyl-mannosamine, N-acetyl-lactosamine, and hydroxyisobutyric acid] was developed for distinguishing early-stage ovarian cancer from BPM. The performance of the metabolite panel was evaluated in an …

Nab-Paclitaxel, Capecitabine, And Radiation Therapy After Induction Chemotherapy In Treating Patients With Locally Advanced And Borderline Resectable Pancreatic Cancer: Phase 1 Trial And Imaging-Based Biomarker Validation, Eugene J Koay, Mohamed Zaid, Maureen Aliru, Polycarpe Bagereka, Arie Van Wieren, Maria Jovie Rodriguez, Galia Jacobson, Robert A Wolff, Michael Overman, Gauri Varadhachary, Shubham Pant, Huamin Wang, Ching-Wei Tzeng, Naruhiko Ikoma, Michael Kim, Jeffrey E Lee, Matthew Hg Katz, Eric Tamm, Priya Bhosale, Cullen M Taniguchi, Emma B Holliday, Grace L Smith, Ethan B Ludmir, Bruce D Minsky, Christopher H Crane, Albert C Koong, Prajnan Das, Xuemei Wang, Milind Javle, Sunil Krishnan

Faculty, Staff and Student Publications

PURPOSE: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response.

METHODS AND MATERIALS: Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m

RESULTS: Twenty-three patients started and finished …

Front Matter

The Synapse: Intercollegiate science magazine

No abstract provided.

The Synapse: Issue 2022

The Synapse: Intercollegiate science magazine

No abstract provided.

The Self-Disorder Model Of Schizophrenia, Sophie Nelson

The Synapse: Intercollegiate science magazine

No abstract provided.

Diseases Hidden In Ice: Ancient Bacteria In Permafrost Could Spread Ancient Diseases, Jessica John

The Synapse: Intercollegiate science magazine

No abstract provided.

“You Can’T Wash Your Hands In A House Without Running Water”: Pandemic Precautionary Behaviors In The Wake Of Hurricane Laura, Cécile Girard

Honors Capstones

No abstract provided.

The Effect Of Biologic Therapy For Immune-Mediated Inflammatory Diseases On Clinical Outcomes Of Covid-19 In The Greater Houston Area: A Retrospective Chart Review, Michela Tinelli, Raphael Wittenberg, Michelle Cornes, Robert W Aldridge, Michael Clark, Richard Byng, Graham Foster, James Fuller, Andrew Hayward, Nigel Hewett, Alan Kilmister, Jill Manthorpe, Joanne Neale, Elizabeth Biswell, Martin Whiteford

Faculty, Staff and Student Publications

There are long-standing concerns that people experiencing homelessness may not recover well if left unsupported after a hospital stay. This study reports on a study investigating the cost-effectiveness of three different 'in patient care coordination and discharge planning' configurations for adults experiencing homelessness who are discharged from hospitals in England. The first configuration provided a clinical and housing in-reach service during acute care and discharge coordination but with no 'step-down' care. The second configuration provided clinical and housing in-reach, discharge coordination and 'step-down' intermediate care. The third configuration consisted of housing support workers providing in-reach and discharge coordination as well …

Comparison Of Setup Accuracy And Efficiency Between The Klarity System And Bodyfix System For Spine Stereotactic Body Radiation Therapy, Enzhuo Quan, Shane P Krafft, Tina M Briere, Marissa J Vaccarelli, Amol J Ghia, Andrew J Bishop, Debra N Yeboa, Todd A Swanson, Eun Young Han

Faculty, Staff and Student Publications

BACKGROUND: Spine stereotactic body radiation therapy (SBRT) uses highly conformal dose distributions and sharp dose gradients to cover targets in proximity to the spinal cord or cauda equina, which requires precise patient positioning and immobilization to deliver safe treatments.

AIMS: Given some limitations with the BodyFIX system in our practice, we sought to evaluate the accuracy and efficiency of the Klarity SBRT patient immobilization system in comparison to the BodyFIX system.

METHODS: Twenty-three patients with 26 metastatic spinal lesions (78 fractions) were enrolled in this prospective observational study with one of two systems - BodyFIX (n = 11) or Klarity …

Research Strategies To Catalyze Agroecological Transitions In Low- And Middle-Income Countries, Sarah K. Jones, Nadia Bergamini, Francesca Beggi, Didier Lesueur, Barbara Vinceti, Arwen Bailey, Fabrice A. Declerck, Natalia Estrada-Carmona, Carlo Fadda, Etienne M. Hainzelin, Danny Hunter, Chris Kettle, Job Kihara, Abdel Kader Naino Jika, Mirjam Pulleman, Roseline Remans, Celine Termote, Tobias Fremout, Evert Thomas, Louis Verchot, Marcela Quintero

All Peer-Reviewed Publications

Governments are updating national strategies to meet global goals on biodiversity, climate change and food systems proposed in the Convention on Biological Diversity post-2020 framework and agreed at the United Nation’s Climate Change Conference (COP26) and Food Systems Summit (UNFSS). This represents a unique and crucial opportunity to integrate and accelerate food system actions to tackle interconnected global challenges. In this context, agroecology is a game-changing approach that can provide the world’s growing population with nutritious, healthy affordable food, ensure fair incomes to farmers and halt and reverse the degradation of the natural environment. Here, we explore agroecological transition pathways …

Inhibition Of Cyclin Dependent Kinase 4/6 Overcomes Primary Resistance To Programmed Cell Death 1 Blockade In Malignant Mesothelioma, Hee-Jin Jang, Cynthia Y Truong, Eric M Lo, Hudson M Holmes, Daniela Ramos, Maheshwari Ramineni, Ju-Seog Lee, Daniel Y Wang, Massimo Pietropaolo, R Taylor Ripley, Bryan M Burt, Hyun-Sung Lee

Faculty, Staff and Student Publications

BACKGROUND: Despite the profound number of malignant pleural mesothelioma (MPM) patients now treated with programmed cell death 1 (PD-1) blockade, insight into the underpinnings of rational therapeutic strategies to treat resistance to checkpoint immunotherapy remains unrealized. Our objective was to develop a novel therapeutic approach to overcome primary resistance to PD-1 blockade in MPM.

METHODS: We generated a transcriptome signature of resistance to PD-1 blockade in MPM patients treated with nivolumab (4 responders and 4 nonresponders). We used The Cancer Genome Atlas MPM cohort (n = 73) to determine what genomic alterations were associated with the resistance signature. We tested …

Investigation Of Murine Host Sex As A Biological Variable In Epithelial Barrier Function And Muscle Contractility In Human Intestinal Organoids, Brooke T Beanland, Eoin P Mcneill, David J Sequeira, Hasen Xue, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

Intestinal failure (IF) occurs when intestinal surface area or function is not sufficient to support digestion and nutrient absorption. Human intestinal organoid (HIO)-derived tissue-engineered intestine is a potential cure for IF. Research to date has demonstrated successful HIO transplantation (tHIO) into mice with significant in vivo maturation. An area lacking in the literature is exploration of murine host sex as a biological variable (SABV) in tHIO function. In this study, we investigate murine host SABV in tHIO epithelial barrier function and muscle contractility. HIOs were generated in vitro and transplanted into nonobese diabetic, severe combined immunodeficiency gamma chain deficient male …

Combined Regulatory T-Lymphocyte And Il-2 Treatment Is Safe, Tolerable, And Biologically Active For 1 Year In Persons With Amyotrophic Lateral Sclerosis, Jason R Thonhoff, James D Berry, Eric A Macklin, David R Beers, Patricia A Mendoza, Weihua Zhao, Aaron D Thome, Fabio Triolo, James J Moon, Sabrina Paganoni, Merit Cudkowicz, Stanley H Appel

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: In a phase 1 amyotrophic lateral sclerosis (ALS) study, autologous infusions of expanded regulatory T-lymphocytes (Tregs) combined with subcutaneous interleukin (IL)-2 were safe and well tolerated. Treg suppressive function increased and disease progression stabilized during the study. The present study was conducted to confirm the reliability of these results.

METHODS: Participants with ALS underwent leukapheresis, and their Tregs were isolated and expanded in a current Good Manufacturing Practice facility. Seven participants were randomly assigned in a 1:1 ratio to receive Treg infusions (1 × 10

RESULTS: The Treg/IL-2 treatments were safe and well tolerated, and Treg suppressive …