Medicine and Health Sciences Commons^™

Translation Of Monosynaptic Circuits Underlying Amygdala Fmri Neurofeedback Training, Lucas Trambaiolli, Chiara Maffei, Evan Dann, Claudinei Biazoli, Gleb Bezgin, Anastasia Yendiki, Suzanne Haber

Faculty, Staff and Student Publications

fMRI neurofeedback using autobiographical memory recall to upregulate the amygdala is associated with resting-state functional connectivity (rsFC) changes between the amygdala and the salience and default mode networks (SN and DMN, respectively). We hypothesize the existence of anatomical circuits underlying these rsFC changes. Using a cross-species brain parcellation, we identified in non-human primates locations homologous to the regions of interest (ROIs) from studies showing pre-to-post-neurofeedback changes in rsFC with the left amygdala. We injected bidirectional tracers in the basolateral, lateral, and central amygdala nuclei of adult macaques and used bright- and dark-field microscopy to identify cells and axon terminals in …

Cross-Species Striatal Hubs: Linking Anatomy To Resting-State Connectivity, Xiaolong Peng, Lucas R Trambaiolli, Eun Young Choi, Julia F Lehman, Gary Linn, Brian E Russ, Charles E Schroeder, Suzanne N Haber, Hesheng Liu

Faculty, Staff and Student Publications

Corticostriatal connections are essential for motivation, cognition, and behavioral flexibility. There is broad interest in using resting-state functional magnetic resonance imaging (rs-fMRI) to link circuit dysfunction in these connections with neuropsychiatric disorders. In this paper, we used tract-tracing data from non-human primates (NHPs) to assess the likelihood of monosynaptic connections being represented in rs-fMRI data of NHPs and humans. We also demonstrated that existing hub locations in the anatomical data can be identified in the rs-fMRI data from both species. To characterize this in detail, we mapped the complete striatal projection zones from 27 tract-tracer injections located in the orbitofrontal …

Analyzing Llama 3-Based Approach For Axiom Translation From Ontologies, Xubing Hao, Licong Cui, Cui Tao, Kirk Roberts, Muhammad Amith

Faculty, Staff and Student Publications

Ontology development involves a top-down approach where ontology engineers and domain experts collaboratively define and evaluate ontological elements and axioms. Translating ontology axioms into natural language can significantly aid in ontology evaluation by making the content more understandable to subject matter experts who may lack a background in knowledge engineering. In this preliminary study, we investigate the potential of large language models (LLMs) in axiom translation from ontologies to facilitate ontology evaluation. We utilize Llama 3 to translate 1,192 ontology axioms across 19 distinct axiom types from five published ontologies. Results show that 163 (13.67%) of the Llama 3 translation …

Genetic Regulation Of Human Brain Proteome Reveals Proteins Implicated In Psychiatric Disorders, Jie Luo, Ling Li, Mingming Niu, Dehui Kong, Yi Jiang, Suresh Poudel, Annie W Shieh, Lijun Cheng, Gina Giase, Kay Grennan, Kevin P White, Chao Chen, Sidney H Wang, Dalila Pinto, Yue Wang, Chunyu Liu, Junmin Peng, Xusheng Wang

Faculty, Staff and Student Publications

Psychiatric disorders are highly heritable yet polygenic, potentially involving hundreds of risk genes. Genome-wide association studies have identified hundreds of genomic susceptibility loci with susceptibility to psychiatric disorders; however, the contribution of these loci to the underlying psychopathology and etiology remains elusive. Here we generated deep human brain proteomics data by quantifying 11,608 proteins across 268 subjects using 11-plex tandem mass tag coupled with two-dimensional liquid chromatography-tandem mass spectrometry. Our analysis revealed 788 cis-acting protein quantitative trait loci associated with the expression of 883 proteins at a genome-wide false discovery rate < 5%. In contrast to expression at the transcript level and complex diseases that are found to be mainly influenced by noncoding variants, we found protein expression level tends to be regulated by non-synonymous variants. We also provided evidence of 76 shared regulatory signals between gene expression and protein abundance. Mediation analysis revealed that for most (88%) of the colocalized genes, the expression levels of their corresponding proteins are regulated by cis-pQTLs via gene transcription. Using summary data-based Mendelian randomization analysis, we identified 4 proteins and 19 genes that are causally associated with schizophrenia. We further integrated multiple omics data with network analysis to prioritize candidate genes for schizophrenia risk loci. Collectively, our findings underscore the potential of proteome-wide linkage analysis in gaining mechanistic insights into the pathogenesis of psychiatric disorders.

Corpus Callosum Structure And Auditory Interhemispheric Transfer In Spina Bifida Myelomeningocele, Kailyn A Bradley, Jenifer J Juranek, H Julia Hannay, Paul T Cirino, Larry A Kramer, Jack M Fletcher

Faculty, Staff and Student Publications

Objective: Maldevelopment of the posterior corpus callosum is common in spina bifida myelomeningocele (SBM) due to hydrocephalus-related hypoplasia and congenital partial hypogenesis. This study examined the relations of macro- and microstructural integrity of the interhemispheric temporal tract in SBM and auditory interhemispheric transfer using consonant-vowel dichotic listening.

Method: We collected T₁-weighted and diffusion tensor imaging data from 46 individuals with SBM and 15 typically developing individuals. Probabilistic tractography was used to isolate the interhemispheric white matter connecting auditory processing regions in both hemispheres. Interhemispheric transfer was assessed with a dichotic listening task.

Results: Although the typically developing group and …

Use Of Peripheral Nerve Blocks For Total Hip Arthroplasty, Leon Grinman, Brett Elmore, Alberto E Ardon, Adnan Hussain, Mohammed Faysal Malik, Nadia Hernandez, Mackenzie Janice Jacoby

Faculty, Staff and Student Publications

Purpose of review: The purpose of this review is to summarize the recent literature regarding regional anesthesia (RA) techniques and outcomes for total hip arthroplasty (THA) in the face of changing surgical techniques and perioperative considerations.

Recent findings: Based on large meta-analyses, peripheral nerve blocks are indicated for THA. Each block has its own risks and benefits and data for outcomes for particular techniques are limited. New surgical techniques, improved use of multimodal analgesia, and improved ultrasound guided regional anesthetics lead to better pain control for patients undergoing THA with less associated risks. Block selection continues to be influenced by …

Increased Gremlin1 Expression In Pancreatic Ductal Adenocarcinoma Promotes A Fibrogenic Stromal Microenvironment, Rachel R Tindall, Erika Y Faraoni, Jiajing Li, Yinjie Zhang, Shun-Ming Ting, Beanna Okeugo, Xiurong Zhao, Yuying Liu, Mamoun Younes, Qiang Shen, Jennifer M Bailey-Lundberg, Yanna Cao, Tien C Ko

Faculty, Staff and Student Publications

Objective: Pancreatic ductal adenocarcinoma (PDAC) microenvironment is primarily composed of cancer-associated fibroblasts and immune cells. Gremlin1 (Grem1) is a profibrogenic factor that promotes tumorigenesis in several cancers. However, the role of Grem1 in the PDAC microenvironment is not defined.

Materials and methods: We correlated Grem1 levels with activated stroma and immune cells in human PDAC using The Cancer Genome Atlas RNA-sequencing data and characterized expression of Grem1 transcripts and isoforms in pancreatic cell lines and PDAC tissues. We assessed the role of Grem1 in the microenvironment by in vitro studies.

Results: Grem1 expression is associated with an activated stroma and …

Durable Local Control With Hypofractionated Radiation Therapy For Unresectable Or Metastatic Melanoma, Sydney A Keatts, Aya F Salem, David M Swanson, Ahsan S Farooqi, Andrew J Bishop, Rodabe N Amaria, Jennifer L Mcquade, Isabella C Glitza Oliva, Adi Diab, Roi Weiser, Sarah B Fisher, Ryan P Goepfert, Merrick I Ross, B Ashleigh Guadagnolo, Devarati Mitra

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: As patients with advanced melanoma live longer in the context of systemic therapy advancements, better strategies for durable control of bulky tumors are needed. In this study, we evaluated if dose-escalated hypofractionated radiation therapy (HFRT) can provide durable local control and improve tumor-associated symptoms in patients with unresectable or bulky metastatic melanoma for whom stereotactic ablative radiotherapy (RT) approaches are not feasible due to tumor size or location.

MATERIALS AND METHODS: We retrospectively reviewed 49 patients with unresectable or bulky metastatic melanoma who were treated to a total of 53 tumor targets with 12-17 fractions HFRT at …

Peak Nasal Inspiratory Flow Assessment Of Polyp Size And Response From Synapse, Amber U Luong, Joshua M Levy, Ludger Klimek, Richard J Harvey, Jared Silver, Steven G Smith, Abby Fuller, Robert Chan, Peter W Hellings

Faculty, Staff and Student Publications

Background: In the phase III SYNAPSE study, mepolizumab plus standard of care reduced total endoscopic nasal polyp score (NPS) versus that with placebo in patients with chronic rhinosinusitis with nasal polyps.

Objective: Our aim was to investigate relationships between NPS and (1) peak nasal inspiratory flow (PNIF) and (2) patient-reported outcomes.

Methods: In this post hoc analysis, patients randomized 1:1 received mepolizumab, 100 mg, or placebo subcutaneously every 4 weeks (plus standard of care). Changes from baseline in PNIF (week 52), visual analog scale scores (overall symptoms, nasal obstruction, and loss of smell [weeks 49-52]), and total 22-Item Sino-Nasal Outcome …

Building Resilience: A Specialty Clinic Tailored To Older Adults At Risk For Violence And Abuse, Melba A Hernandez-Tejada, Deborah M Little, Madeline J Bruce, Sarly Butte, Jason Burnett, Leila Wood, Ron Acierno

Faculty, Staff and Student Publications

Objective: Both structural (e.g., ageism) and personal (e.g., stigma) barriers hinder older adults' access to and engagement with mental health care. These barriers are particularly problematic for those vulnerable to interpersonal violence and abuse (e.g., due to social isolation). This study presents a quality improvement program aimed at older adults who have experienced significant stressful events, particularly elder mistreatment, within a larger trauma specialty clinic. Leveraging home-based telemedicine, the clinic provides evidence-based psychotherapy tailored to the needs of older adults.

Methods: From 2021 through 2023, the authors retrospectively examined treatment initiation, engagement, completion, and clinical outcomes among 231 older adults …

Comparative Effectiveness Of Non-Compounded Polidocanol 1% Endovenous Microfoam (Varithena) Ablation Versus Endovenous Thermal Ablation Utilizing A Systematic Review And Network Meta-Analysis, Lowell S Kabnick, Juan Carlos Jimenez, Sheila M Coogan, Larry Gache, Diana Frame, Candace Gunnarsson, Kathleen Ozsvath

Faculty, Staff and Student Publications

Objective: We compared the effectiveness and safety of polidocanol 1% endovenous microfoam ablation vs endovenous thermal ablation with radiofrequency or laser energy for treatment of venous insufficiency caused by lower extremity truncal vein incompetence via network meta-analysis of published comparative evidence.

Methods: We conducted a systematic literature review following best practices, including a prospective protocol. We screened studies published in English from 2000 to 2023 for randomized and nonrandomized studies reporting direct or indirect comparisons between polidocanol 1% endovenous microfoam and endovenous thermal ablation. Thirteen studies met our eligibility criteria for the network meta-analysis. The co-primary effectiveness outcomes were the …

White Matter And Latency Of Visual Evoked Potentials During Maturation: A Miniature Pig Model Of Adolescent Development, Peter Kochunov, L Elliot Hong, Ann Summerfelt, Si Gao, P Leon Brown, Matthew Terzi, Ashley Acheson, Marty G Woldorff, Els Fieremans, Ali Abdollahzadeh, Korrapati V Sathyasaikumar, Sarah M Clark, Robert Schwarcz, Paul D Shepard, Greg I Elmer

Faculty, Staff and Student Publications

Background: Continuous myelination of cerebral white matter (WM) during adolescence overlaps with the formation of higher cognitive skills and the onset of many neuropsychiatric disorders. We developed a miniature-pig model of adolescent brain development for neuroimaging and neurophysiological assessment during this critical period. Minipigs have gyroencephalic brains with a large cerebral WM compartment and a well-defined adolescence period.

Methods: Eight Sinclair™ minipigs (Sus scrofa domestica) were evaluated four times during weeks 14-28 (40, 28 and 28 days apart) of adolescence using monocular visual stimulation (1 Hz)-evoked potentials and diffusion MRI (dMRI) of WM. The latency for the pre-positive 30 ms …

Increased White Blood Cell In Young Adults With Family Histories Of Alcohol And Other Substance Use Disorders, Mustafa N Mithaiwala, Nikki S Phillips, Dylan H Nguyen, Melanie S Beehler, Harrison S Ballard, Andrea S Vincent, William R Lovallo, Peter Kochunov, L Elliot Hong, Jason C O'Connor, Steve Cole, Ashley Acheson

Faculty, Staff and Student Publications

Individuals with a family history of alcohol or other substance use disorders (FH+) are at increased risk for developing alcohol and other substance use disorders (AUD/SUD) compared to individuals with no such family histories (FH-). FH+ young adults have blunted stress reactivity, lower cognitive performance and altered frontal white matter microstructure compared to FH- controls. We hypothesized that family history of AUD/SUD disrupts neuroendocrine regulation of the immune system in FH+ individuals, resulting in altered blood immune cell composition, inflammation and neurocognitive alterations that, ultimately, increases risk for AUD/SUD and associated psychopathology. We examined white blood cell (WBC) parameters derived …

Diaphragmatic Myopathy Associated With Dual Immune Checkpoint Inhibitors In A Patient With Renal Cell Carcinoma, Jeremy R Walder, Saadia A Faiz, Sudhakar Tummala, Shiao-Pei Weathers, Nicolas L Palaskas, Maryam Buni, Ajay Sheshadri, Lara Bashoura

Faculty, Staff and Student Publications

Immune-related adverse events (irAEs) have become increasingly prevalent with immune checkpoint inhibitor (ICI) cancer treatment. We present a 79-year-old man with metastatic renal cell carcinoma who developed shortness of breath and hypercapnic respiratory insufficiency after his first cycle of nivolumab and ipilimumab. Laboratory data showed elevated creatinine kinase, troponins, and transaminases. Computed tomography of the chest demonstrated bilateral lower lobe atelectasis. Heart catheterization and endomyocardial biopsy were unremarkable. Electromyogram (EMG) and nerve conduction studies (NCS) of the limb muscles revealed mild diffuse myopathy, normal sensory nerve conductions, and low-amplitude motor responses. Subsequent diaphragmatic EMG and NCS demonstrated severe myopathy. ICI-mediated …

A Putative Camp-Binding Protein In Trypanosoma Brucei Cooperates With Flam3 To Promote Flagellar Connection And Cell Morphogenesis, Qing Zhou, Phu Van Nguyen, Ziyin Li

Faculty, Staff and Student Publications

Trypanosoma brucei is a flagellated parasitic protozoan, and within the insect vector the parasite transitions from the trypomastigote form to the epimastigote form by repositioning its mitochondrial genome and relocating the flagellum. The mechanisms underlying such morphology changes are still poorly understood, but several flagellum-localized proteins are involved in this process by modulating the flagellum attachment zone (FAZ) that adheres the flagellum to the cell membrane. We report here a putative cAMP-binding protein named cAMP-BP1, which promotes flagellar connection and morphology transition. cAMP-BP1 contains two cyclic nucleotide-binding domains and five calcium-binding C2 domains and localizes to the flagella connector and …

Discovery, Characterization, And Structure Of A Cofactor-Independent Histidine Racemase From The Oral Pathogen Fusobacterium Nucleatum, Tess Lamer, Pu Chen, Marie J Venter, Marco J Van Belkum, Anjalee Wijewardane, Chenggang Wu, M Joanne Lemieux, John C Vederas

Faculty, Staff and Student Publications

Fusobacterium nucleatum is an oral commensal bacterium that can act as an opportunistic pathogen and is implicated in diseases such as periodontitis, adverse pregnancy outcomes, colorectal cancer, and Alzheimer's disease. F. nucleatum synthesizes lanthionine for its peptidoglycan, rather than meso-2,6-diaminopimelic acid (DAP) used by most Gram-negative bacteria. Despite lacking the biosynthetic pathway for DAP, the genome of F. nucleatum ATCC 25586 encodes a predicted DAP epimerase. A recent study hypothesized that this enzyme may act as a lanthionine epimerase, but the authors found a very low turnover rate, suggesting that this enzyme likely has another more favored substrate. Here, we …

The Evolving Pathophysiology Of Tbi And The Advantages Of Temporally-Guided Combination Therapies, Laura Zima, Anthony N Moore, Paul Smolen, Nobuhide Kobori, Brian Noble, Dustin Robinson, Kimberly N Hood, Ryota Homma, Amar Al Mamun, John B Redell, Pramod K Dash

Faculty, Staff and Student Publications

Several clinical and experimental studies have demonstrated that traumatic brain injury (TBI) activates cascades of biochemical, molecular, structural, and pathological changes in the brain. These changes combine to contribute to the various outcomes observed after TBI. Given the breadth and complexity of changes, combination treatments may be an effective approach for targeting multiple detrimental pathways to yield meaningful improvements. In order to identify targets for therapy development, the temporally evolving pathophysiology of TBI needs to be elucidated in detail at both the cellular and molecular levels, as it has been shown that the mechanisms contributing to cognitive dysfunction change over …

Perceived Partner Responsiveness Alters The Association Between Marital Distress And Well-Being In Dementia Spousal Caregivers, Vincent D Lai, Jensine Paoletti-Hatcher, E Lydia Wu-Chung, Itee Mahant, Daniel L Argueta, Kelly N Brice, Bryan T Denny, Charles Green, Luis D Medina, Paul E Schulz, Jennifer M Stinson, Cobi J Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Caregivers for spouses with Alzheimer's disease and related dementias (ADRD) experience drastic changes in the marital relationship that may put them at risk for worsening well-being. Perceived partner responsiveness, or feeling cared for, understood, and appreciated by one's spouse, may help mitigate these effects. In this study, we investigated the associations between marital distress, perceived partner responsiveness, and psychological and physiological well-being indicators among ADRD spousal caregivers.

Method: A sample of 161 caregivers provided blood samples and completed self-report measures of marital distress, perceived partner responsiveness, and depressive symptoms. We tested hypotheses in our sample cross-sectionally based on two theoretical …

Clinical Profile Of Patients With Acute Traumatic Brain Injury Undergoing Cranial Surgery In The United States: Report From The 18-Centre Track-Tbi Cohort Study, John K Yue, John H Kanter, Jason K Barber, Michael C Huang, Thomas A Van Essen, Mahmoud M Elguindy, Brandon Foreman, Frederick K Korley, Patrick J Belton, Dana Pisică, Young M Lee, Ryan S Kitagawa, Mary J Vassar, Xiaoying Sun, Gabriela G Satris, Justin C Wong, Adam R Ferguson, J Russell Huie, Kevin K W Wang, Hansen Deng, Vincent Y Wang, Yelena G Bodien, Sabrina R Taylor, Debbie Y Madhok, Michael A Mccrea, Laura B Ngwenya, Anthony M Digiorgio, Phiroz E Tarapore, Murray B Stein, Ava M Puccio, Joseph T Giacino, Ramon Diaz-Arrastia, Hester F Lingsma, Pratik Mukherjee, Esther L Yuh, Claudia S Robertson, David K Menon, Andrew I R Maas, Amy J Markowitz, Sonia Jain, David O Okonkwo, Nancy R Temkin, Geoffrey T Manley, Track-Tbi Investigators

Faculty, Staff and Student Publications

Background: Contemporary surgical practices for traumatic brain injury (TBI) remain unclear. We describe the clinical profile of an 18-centre US TBI cohort with cranial surgery.

Methods: The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (2014-2018; ClinicalTrials.gov #NCT02119182) enrolled subjects who presented to trauma centre and received head computed tomography within 24-h (h) post-TBI. We performed a secondary data analysis in subjects aged ≥17-years with hospitalisation. Clinical characteristics, surgery type/timing, hospital and six-month outcomes were reported.

Findings: Of 2032 subjects (age: mean = 41.4-years, range = 17-89-years; male = 71% female = 29%), 260 underwent …

Association Between Metformin Use In Early Gestational Or Type 2 Diabetes In Pregnancy And Preterm Preeclampsia, Maya Patel, Ashley N Battarbee, Jerrie S Refuerzo, Noelia Zork, Kacey Eichelberger, Gladys A Ramos, Gayle Olson, Celeste Durnwald, Mark B Landon, Kjersti M Aagaard, Kedra Wallace, Christina Scifres, Todd Rosen, Wadia Mulla, Amy Valent, Sherri Longo, Kim A Boggess

Faculty, Staff and Student Publications

Objective: To estimate the association between maternal metformin use for the treatment of early gestational or pre-existing type 2 diabetes and preterm preeclampsia.

Methods: This is a planned secondary analysis of the MOMPOD study (Medical Optimization of Management of Overt Type 2 Diabetes in Pregnancy), a randomized trial comparing the effect of adding metformin with insulin treatment on composite neonatal outcome in singleton pregnancies with early gestational or type 2 diabetes. Participants were randomized at 11-23 weeks of gestation to 1,000 mg metformin twice daily or placebo until delivery. A subset of participants had maternal blood collected at 24-30 weeks …

Learning The Hard Way: The Business Of Hand Surgery, Noah M Raizman, James M Saucedo

Faculty, Staff and Student Publications

No abstract provided.

Axial Imaging In Spondyloarthritis, Vishnu Mohan, Mark C Hwang

Faculty, Staff and Student Publications

Imaging plays a crucial role in diagnosing and forecasting treatment outcomes in axial spondyloarthritis. Conventional radiography may overlook patients in the initial stages of the disease, while MRI is sensitive in identifying inflammation early on. Computed tomography reliably detects structural abnormalities. Practicing rheumatologists must possess a fundamental understanding of interpreting both active inflammatory and structural lesions in axial spondyloarthritis.

Glymphatic Dysfunction In Multiple Sclerosis And Its Association With Disease Pathology And Disability, Ahmed Bayoumi, Khader M Hasan, Joseph A Thomas, Akram Yazdani, John A Lincoln

Faculty, Staff and Student Publications

Background: The role of the glymphatic system in multiple sclerosis (MS)-related disability remains underexplored. Diffusion-tensor image analysis along the perivascular space (DTI-ALPS) offers a non-invasive method to assess glymphatic function.

Objective: To evaluate glymphatic function in MS patients with lower and higher disability.

Methods: This study included 118 MS patients who underwent structural, diffusion-weighted imaging, and clinical assessment. The participants were divided into lower (MS-L, n = 57) and higher disability (MS-H, n = 61) subgroups. Brain parenchymal fraction (BPF), lesion load (LL), and DTI-ALPS index were measured. Subgroup differences and correlations between DTI-ALPS index and other measures were explored. …

Bacillus Licheniformis Suppresses Clostridium Perfringens Infection Via Modulating Inflammatory Response, Antioxidant Status, Inflammasome Activation And Microbial Homeostasis In Broilers, Xiao Xiao, Songke Qin, Tiantian Cui, Jinsong Liu, Yanping Wu, Yifan Zhong, Caimei Yang

Faculty, Staff and Student Publications

Pathogenic bacteria infection, especially Clostridium perfringens (C. perfringens), markedly threatened the health of animals, and further caused huge economic loss. In this study, Bacillus licheniformis HJ0135 (BL) was used. Oxford cup bacteriostatic test and inhibitory rate test were conducted to evaluate the antibacterial ability of BL. Results showed the strongest inhibitory role of BL on C. perfringens (P < 0.05). Afterwards, 540 one-day-old yellow-feather broilers (32.7 ± 0.2 g) were randomly allocated into 3 groups, including CON group (basal diet), CP group (basal diet + 1 × 109 CFU C. perfringens in gavage), and BL + CP group (basal diet containing 7.5 × 106 CFU/g BL + 1 × 109 CFU C. perfringens in gavage). At d 70, broilers in the CP and BL + CP groups were treated with C. perfringens by continuously oral administration for 5 d. The experiment lasted for 75 d. The serum, immune organs, jejunal mucosa, and cecal contents were collected for analysis. In vivo experiment showed that BL supplementation markedly improved (P < 0.05) BW, ADG, thymus index, serum immunoglobins and antioxidases, reduced feed conversion ratio (FCR) and serum pro-inflammatory cytokines of C. perfringens-infected broilers. Furthermore, the increased jejunal injury and levels of pro-inflammatory cytokines, decreased gene expressions of tight junction proteins in the jejunal mucosa were significantly alleviated (P < 0.05) by BL. More importantly, the activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome was inhibited (P < 0.05) by BL to further attenuate jejunal damage. Besides, BL supplementation markedly increased (P < 0.05) the cecal isobutyric acid and isovaleric acid. Microbial analysis showed that BL changed the composition and relative abundances of microbiota in the cecal contents (P < 0.05), especially the short chain fatty acids (SCFAs)-producing bacteria including Eubacterium_coprostanoligenes_group, Megamonas, Faecalibacterium, and Lactobacillus, which further protected against C. perfringens-induced jejunal inflammation in broilers. Our study laid a theoretical basis for the application of probiotics in lessening C. perfringens-related diseases in poultry farming.

Hu8f4-Car T Cells With Mutated Fc Spacer Segment Improve Target Specificity And Mediate Anti-Leukemia Activity In Vivo, Hong He, Rolando A Vedia, Sijie Lu, Qiaochuan Li, Kathryn R Cox, Lisa St John, Anna Sergeeva, Karen Clise-Dwyer, Gheath Alatrash, Elizabeth J Shpall, Qing Ma, Jeffrey J Molldrem

Faculty, Staff and Student Publications

Background aims: Hu8F4 is a T-cell receptor-like antibody with high affinity for the leukemia-associated antigen PR1/HLA-A2 epitope. Adapted into a chimeric antigen receptor (CAR) format, Hu8F4-CAR is composed of the Hu8F4 single-chain variable fragment, the human IgG1 CH2CH3 extracellular spacer domain, a human CD28 costimulatory domain and the human CD3ζ signaling domain. We have demonstrated high efficacy of Hu8F4-CAR-T cells against PR1/HLA-A2-expressing cell lines and leukemic blasts from patients with acute myeloid leukemia in vitro. Previous studies have shown that modification of the Fc domains of IgG4 CH2CH3 spacer regions can eliminate activation-induced cell death and off-target killing mediated by …

Results Of A Randomized Phase Ii Trial Of Paclitaxel And Carboplatin Versus Bleomycin, Etoposide And Cisplatin For Newly Diagnosed And Recurrent Chemonaive Stromal Ovarian Tumors: An Nrg Oncology/Gynecologic Oncology Group Study14, Jubilee Brown, Austin Miller, Laura L Holman, Floor Backes, Christa Nagel, David Bender, David S Miller, Matthew A Powell, Shannon N Westin, Albert Bonebrake, Carolyn Y Muller, Angeles Alvarez Secord, Erin Crane, John Schorge, William P Tew, Anil K Sood, Michael A Bookman, Carol Aghajanian, David M Gershenson

Faculty, Staff and Student Publications

Objectives: To assess the efficacy and toxicity of paclitaxel and carboplatin (PC) compared to bleomycin, etoposide, and cisplatin (BEP) for treatment of newly diagnosed Stage IIA-IV or recurrent chemotherapy-naive ovarian sex cord-stromal tumors (SCST).

Methods: This phase II noninferiority trial randomly assigned patients to receive PC (6 cycles P 175 mg/m2 and C AUC = 6 IV every 3 weeks), or BEP (4 cycles B 20 units/m2 IV push day 1, E 75 mg/m2 IV days 1-5, and cisplatin 20 mg/m2 IV days 1-5 every 3 weeks). The primary endpoint was progression- free survival (PFS). This trial is registered with …

Uterine-Conserving Treatment Options For Atypical Endometrial Hyperplasia And Early Endometrial Cancer, Naomi N Adjei, Mikayla Borthwick Bowen, Roni Nitecki Wilke, Melinda S Yates, Shannon N Westin

Faculty, Staff and Student Publications

Purpose of review: This review aims to synthesize available literature on uterine-conserving treatment options for atypical endometrial hyperplasia and grade 1 endometrial carcinoma while highlighting remaining unanswered questions.

Recent findings: The need for uterine-conserving treatment options for atypical endometrial hyperplasia and grade 1 endometrial carcinoma is growing with the increasing number of cases in younger patients or those who cannot undergo surgery. We reviewed the oncological and reproductive outcomes associated with endocrine therapies used for atypical endometrial hyperplasia and grade 1 endometrial carcinoma. The rising prevalence of delayed childbearing, obesity, and diabetes in reproductive-age individuals and of medical comorbidities associated …

Availability Of Lasers And Hands-On Training In Cosmetic Dermatology In Residency, Bianca Y Kang, Erik J Stratman, Jenny C Hu, Rachel Elsanadi, Tanya Greywal, Kristen M Kelly, Arisa Ortiz, Sami K Saikaly, Kathleen C Suozzi, Diana Bolotin, Kira Minkis, Murad Alam

Faculty, Staff and Student Publications

No abstract provided.

Consensus Molecular Subtyping Of Metastatic Colorectal Cancer Expands Biomarker-Directed Therapeutic Benefit For Patients With Cms1 And Cms2 Tumors, Saikat Chowdhury, Joanne Xiu, Jennifer R Ribeiro, Theodore Nicolaides, Jian Zhang, W Michael Korn, Kelsey A Poorman, Heinz-Josef Lenz, John L Marshall, Matthew J Oberley, George W Sledge, David Spetzler, Scott Kopetz, John Paul Shen

Faculty, Staff and Student Publications

Background: We developed a whole transcriptome sequencing (WTS)-based Consensus Molecular Subtypes (CMS) classifier using FFPE tissue and investigated its prognostic and predictive utility in a large clinico-genomic database of CRC patients (n = 24,939).

Methods: The classifier was trained against the original CMS datasets using an SVM model and validated in an independent blinded TCGA dataset (88.0% accuracy). Kaplan-Meier estimates of overall survival (OS) and time-on-treatment (TOT) were calculated for each CMS (p < 0.05 considered significant).

Results: CMS2 tumors were enriched on left-side of colon and conferred the longest median OS. In RAS-wildtype mCRC, left-sided tumors and CMS2 classification were associated with longer …

A Novel Statistical Framework For Meta-Analysis Of Total Mediation Effect With High-Dimensional Omics Mediators In Large-Scale Genomic Consortia, Zhichao Xu, Peng Wei

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Meta-analysis is used to aggregate the effects of interest across multiple studies, while its methodology is largely underexplored in mediation analysis, particularly in estimating the total mediation effect of high-dimensional omics mediators. Large-scale genomic consortia, such as the Trans-Omics for Precision Medicine (TOPMed) program, comprise multiple cohorts with diverse technologies to elucidate the genetic architecture and biological mechanisms underlying complex human traits and diseases. Leveraging the recent established asymptotic standard error of the R-squared (R2)-based mediation effect estimation for high-dimensional omics mediators, we have developed a novel meta-analysis framework requiring only summary statistics and allowing inter-study heterogeneity. Whereas the proposed …