Digital Commons Network^™

Genetic Correlations Between Alzheimer’S Disease And Gut Microbiome Genera, Davis Cammann, Yimei Lu, Melika J Cummings, Mark L Zhang, Joan Manuel Cue, Jenifer Do, Jeffrey Ebersole, Xiangning Chen, Edwin C Oh, Jeffrey L Cummings, Jingchun Chen

Faculty, Staff and Student Publications

A growing body of evidence suggests that dysbiosis of the human gut microbiota is associated with neurodegenerative diseases like Alzheimer's disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual's risk for the disease. Using the largest genome-wide …

Genome-Wide Crispr Screens Reveal Zatt As A Synthetic Lethal Target Of Top2-Poison Etoposide That Can Act In A Tdp2-Independent Pathway, Jeong-Min Park, Huimin Zhang, Litong Nie, Chao Wang, Min Huang, Xu Feng, Mengfan Tang, Zhen Chen, Yun Xiong, Namsoo Lee, Siting Li, Ling Yin, Traver Hart, Junjie Chen

Faculty, Staff and Student Publications

Etoposide (ETO) is an anticancer drug that targets topoisomerase II (TOP2). It stabilizes a normally transient TOP2-DNA covalent complex (TOP2cc), thus leading to DNA double-strand breaks (DSBs). Tyrosyl-DNA phosphodiesterases two (TDP2) is directly involved in the repair of TOP2cc by removing phosphotyrosyl peptides from 5'-termini of DSBs. Recent studies suggest that additional factors are required for TOP2cc repair, which include the proteasome and the zinc finger protein associated with TDP2 and TOP2, named ZATT. ZATT may alter the conformation of TOP2cc in a way that renders the accessibility of TDP2 for TOP2cc removal. In this study, our genome-wide clustered regularly …

The Prognostic Value Of Baseline Clinical And Radiologic Imaging Features In Patients With Unresectable Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab, Mikhail Bogdanov

Faculty, Staff and Student Publications

Membrane asymmetry means that the two sides of membrane are structurally, physically and functionally different. Membrane asymmetry is largely related to the lipid sidedness and particularly to compositional (lipid head and acyl group) and physical (lipid packing order, charge, hydration and H-bonding interactions) differences in the inner and outer leaflets of lipid bilayer. Chemically, structurally and conformationally different non-covalent bound lipid molecules are physically fluid and deformable and enable to interact dynamically to form transient arrangements with asymmetry both perpendicular and parallel to the plane of the lipid bilayer. Although biological membranes are almost universally asymmetric however the asymmetry is …

Damaged Mitochondria Coincide With Presynaptic Vesicle Loss And Abnormalities In Alzheimer’S Disease Brain, Wenzhang Wang, Fanpeng Zhao, Yubing Lu, Sandra L Siedlak, Hisashi Fujioka, Hao Feng, George Perry, Xiongwei Zhu

Faculty, Staff and Student Publications

Loss of synapses is the most robust pathological correlate of Alzheimer's disease (AD)-associated cognitive deficits, although the underlying mechanism remains incompletely understood. Synaptic terminals have abundant mitochondria which play an indispensable role in synaptic function through ATP provision and calcium buffering. Mitochondrial dysfunction is an early and prominent feature in AD which could contribute to synaptic deficits. Here, using electron microscopy, we examined synapses with a focus on mitochondrial deficits in presynaptic axonal terminals and dendritic spines in cortical biopsy samples from clinically diagnosed AD and age-matched non-AD control patients. Synaptic vesicle density within the presynaptic axon terminals was significantly …

Environmental Enrichment Devices Are Safe And Effective At Reducing Undesirable Behaviors In California Sea Lions And Northern Elephant Seals During Rehabilitation, Kirsten Donald, Amanda Benedetti, Vinícius Donisete Lima Rodrigues Goulart, Alissa Deming, Hendrik Nollens, Grey Stafford, Sabrina Brando

Faculty, Staff and Student Publications

Environmental enrichment devices (EEDs) have been proven to promote positive wellbeing in zoos and aquariums, and support animals' reintroduction success; however, their use in rehabilitation centers is still limited. This pilot study investigated the safety and efficacy of three EEDs, Artificial Kelp, Horse KONG™ and Wubba Kong™, and their ability to decrease and/or eliminate undesired stereotypic behaviors or looking at staff/staff areas in seven wild California sea lions (CSLs) and eight northern elephant seals (NESs) undergoing rehabilitation in Southern California. Observers conducted instantaneous sampling once a minute during a 30-min baseline, followed by a 30-min EED implementation on one focal …

Renovating A Double Fence With Or Without Notifying The Next Door And Across The Street Neighbors: Why The Biogenic Cytoplasmic Membrane Of Gram-Negative Bacteria Display Asymmetry?, Mikhail Bogdanov

Faculty, Staff and Student Publications

The complex two-membrane organization of the envelope of Gram-negative bacteria imposes an unique biosynthetic and topological constraints that can affect translocation of lipids and proteins synthesized on the cytoplasm facing leaflet of the cytoplasmic (inner) membrane (IM), across the IM and between the IM and outer membrane (OM). Balanced growth of two membranes and continuous loss of phospholipids in the periplasmic leaflet of the IM as metabolic precursors for envelope components and for translocation to the OM requires a constant supply of phospholipids in the IM cytosolic leaflet. At present we have no explanation as to why the biogenic E. …

Visualizing Lipid Membrane Structure With Cryo-Em: Past, Present, And Future, Karan D Sharma, Frederick A Heberle, M Neal Waxham

Faculty, Staff and Student Publications

The development of electron cryomicroscopy (cryo-EM) has evolved immensely in the last several decades and is now well-established in the analysis of protein structure both in isolation and in their cellular context. This review focuses on the history and application of cryo-EM to the analysis of membrane architecture. Parallels between the levels of organization of protein structure are useful in organizing the discussion of the unique parameters that influence the collective behavior that influences membrane structure and function. Importantly, the timescales of lipid motion in bilayers with respect to the timescales of sample vitrification is discussed and reveals what types …

Renovating A Double Fence With Or Without Notifying The Next Door And Across The Street Neighbors: Why The Biogenic Cytoplasmic Membrane Of Gram-Negative Bacteria Display Asymmetry?, Mikhail Bogdanov

Faculty, Staff and Student Publications

The complex two-membrane organization of the envelope of Gram-negative bacteria imposes an unique biosynthetic and topological constraints that can affect translocation of lipids and proteins synthesized on the cytoplasm facing leaflet of the cytoplasmic (inner) membrane (IM), across the IM and between the IM and outer membrane (OM). Balanced growth of two membranes and continuous loss of phospholipids in the periplasmic leaflet of the IM as metabolic precursors for envelope components and for translocation to the OM requires a constant supply of phospholipids in the IM cytosolic leaflet. At present we have no explanation as to why the biogenic E. …

Targeting The Molecular And Immunologic Features Of Leiomyosarcoma, Brandon M Cope, Raymond S Traweek, Rossana Lazcano, Emily Z Keung, Alexander J Lazar, Christina L Roland, Elise F Nassif

Faculty, Staff and Student Publications

Leiomyosarcoma (LMS) is a rare, aggressive mesenchymal tumor with smooth muscle differentiation. LMS is one of the most common histologic subtypes of soft tissue sarcoma; it most frequently occurs in the extremities, retroperitoneum, or uterus. LMS often demonstrates aggressive tumor biology, with a higher risk of developing distant metastatic disease than most sarcoma histologic types. The prognosis is poor, particularly in patients with uterine disease, and there is a need for the development of more effective therapies. Genetically, LMS is karyotypically complex and characterized by a low tumor mutational burden, with frequent alterations in TP53, RB1, PTEN, …

Efficacy Of A Relaxation Scenario In Virtual Reality For The Comorbid Symptoms Of Anxiety And Asthenia In A General Hospital Setting: A Pilot Comparative Randomized Open-Label Study, Taisiya А Lepilkina, Allan G Beniashvili, Roman A Cheremin, Natalya G Malyukova, Margarita A Morozova, Mikhail A Bogdanov, Denis S Burminsky, Sergei S Potanin, Svetlana V Rodkina, George E Rupchev, Margarita N Eip

Faculty, Staff and Student Publications

BACKGROUND: Patients in general hospitals often display concomitant signs of mental maladjustment: low mood, anxiety, apathy, asthenia, all of which can have a negative impact on the course of the underlying disease and the recovery process. One of the non-pharmacological approaches that has gained wider acceptance in medical practice in recent years is the use of procedures based on virtual reality.

AIM: Assess the efficacy of the new domestic, virtual reality application Flow as relates to symptoms of anxiety and asthenia in patients undergoing inpatient treatment.

METHODS: The study was open-label and had a comparison group; the patients were assigned …

Reconstruction Of Critical Sized Maxillofacial Defects Using Composite Allogeneic Tissue Engineering: Systematic Review Of Current Literature, Shaqayeq Ramezanzade, Mahsa Aeinehvand, Heliya Ziaei, Zohaib Khurshid, Seied Omid Keyhan, Hamid R Fallahi, James C Melville, Morvarid Saeinasab, Farshid Sefat

Faculty, Staff and Student Publications

The current review aimed to assess the reliability and efficacy of tissue-engineered composite grafts in the reconstruction of large maxillofacial defects resulting from trauma or a benign pathologic disease. A systematic review of the literature was conducted using PubMed/Medline, Embase, and Scopus up to March 2022. The eligibility criteria included patients who had been treated with composite allogeneic tissue engineering for immediate/delayed reconstruction of large maxillofacial defects with minimum/no bone harvesting site. In the initial search, 2614 papers were obtained, and finally, 13 papers were eligible to be included in the current study. Most included papers were case reports or …

Covariate-Specific Evaluation Of Continuous Biomarker, Ziyi Li, Yijian Huang, Dattatraya Patil, Mark Rubin, Martin G Sanda

Faculty, Staff and Student Publications

Diagnostic tests usually need to operate at a high sensitivity or specificity level in practice. Accordingly, specificity at the controlled sensitivity, or vice versa, is a clinically sensible performance metric for evaluating continuous biomarkers. Meanwhile, the performance of a biomarker may vary across sub-populations as defined by covariates, and covariate-specific evaluation can be informative. In this article, we develop a novel modeling and estimation method for covariate-specific specificity at a controlled sensitivity level. Unlike existing methods which typically adopt elaborate models of covariate effects over the entire biomarker distribution, our approach models covariate effects locally at a specific sensitivity level …

Interaction Analysis Of Ancestry-Enriched Variants With Apoe-Ɛ4 On Mci In The Study Of Latinos-Investigation Of Neurocognitive Aging, Einat Granot-Hershkovitz, Rui Xia, Yunju Yang, Brian Spitzer, Wassim Tarraf, Priscilla M Vásquez, Richard B Lipton, Martha Daviglus, Maria Argos, Jianwen Cai, Robert Kaplan, Myriam Fornage, Charles Decarli, Hector M Gonzalez, Tamar Sofer

Faculty, Staff and Student Publications

APOE-ɛ4 risk on Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) differs between race/ethnic groups, presumably due to ancestral genomic background surrounding the APOE locus. We studied whether African and Amerindian ancestry-enriched genetic variants in the APOE region modify the effect of the APOE-ɛ4 alleles on Mild Cognitive Impairment (MCI) in Hispanics/Latinos. We defined African and Amerindian ancestry-enriched variants as those common in one Hispanic/Latino parental ancestry and rare in the other two. We identified such variants in the APOE region with a predicted moderate impact based on the SnpEff tool. We tested their interaction with APOE-ɛ4 on MCI in …

The Emergence Of A Virus Variant: Dynamics Of A Competition Model With Cross-Immunity Time-Delay Validated By Wastewater Surveillance Data For Covid-19, Bruce Pell, Samantha Brozak, Tin Phan, Fuqing Wu, Yang Kuang

Faculty, Staff and Student Publications

We consider the dynamics of a virus spreading through a population that produces a mutant strain with the ability to infect individuals that were infected with the established strain. Temporary cross-immunity is included using a time delay, but is found to be a harmless delay. We provide some sufficient conditions that guarantee local and global asymptotic stability of the disease-free equilibrium and the two boundary equilibria when the two strains outcompete one another. It is shown that, due to the immune evasion of the emerging strain, the reproduction number of the emerging strain must be significantly lower than that of …

Dissemination And Implementation Of A Text Messaging Campaign To Improve Health Disparities Among Im/Migrant Workers, Ellie Cherryhomes, Shannon Guillot-Wright

Faculty, Staff and Student Publications

The use of short message service (SMS) text messaging technology has grown in popularity over the last twenty years, but there is limited data on the design and feasibility of campaigns to reduce work-related injury, particularly among rural workers, non-native English speakers, and illiterate or low-literacy populations. Although there is a critical need for tech equity or 'TechQuity' interventions that reduce injury and enhance the wellbeing of under-reached communities, the barriers and benefits to implementation must be empirically and systematically examined. Thus, our team used D&I science to design and implement an 18-week texting campaign for under-reached workers with a …

Geographic Variations And The Associated Factors In Adherence To And Persistence With Adjuvant Hormonal Therapy For The Privately Insured Women Aged 18-64 With Breast Cancer In Texas, Junghyun Kim, Man S Kim, Suja S Rajan, Xianglin L Du, Luisa Franzini, Tae Gi Kim, Sharon H Giordano, Robert O Morgan

Faculty, Staff and Student Publications

The purpose of this study is to examine the geographical patterns of adjuvant hormonal therapy adherence and persistence and the associated factors in insured Texan women aged 18-64 with early breast cancer. A retrospective cohort study was conducted using 5-year claims data for the population insured by the Blue Cross Blue Shield of Texas (BCBSTX). Women diagnosed with early breast cancer who were taking tamoxifen or aromatase inhibitors (AIs) for adjuvant hormonal therapy with at least one prescription claim were identified. Adherence to adjuvant hormonal therapy and persistence with adjuvant hormonal therapy were calculated as outcome measures. Women without a …

Inferring Gene Regulatory Networks From Rna-Seq Data Using Kernel Classification, Amira Al-Aamri, Andrzej S Kudlicki, Maher Maalouf, Kamal Taha, Dirar Homouz

Faculty, Staff and Student Publications

Gene expression profiling is one of the most recognized techniques for inferring gene regulators and their potential targets in gene regulatory networks (GRN). The purpose of this study is to build a regulatory network for the budding yeast Saccharomyces cerevisiae genome by incorporating the use of RNA-seq and microarray data represented by a wide range of experimental conditions. We introduce a pipeline for data analysis, data preparation, and training models. Several kernel classification models; including one-class, two-class, and rare event classification methods, are used to categorize genes. We test the impact of the normalization techniques on the overall performance of …

Hpv-Related Anal Cancer Is Associated With Changes In The Anorectal Microbiome During Cancer Development, Jacob H Elnaggar, Victoria O Huynh, Daniel Lin, R Tyler Hillman, Chike O Abana, Molly B El Alam, Katarina C Tomasic, Tatiana V Karpinets, Ramez Kouzy, Jae L Phan, Jennifer Wargo, Emma B Holliday, Prajnan Das, Melissa P Mezzari, Nadim J Ajami, Erica J Lynn, Bruce D Minsky, Van K Morris, Andrea Milbourne, Craig A Messick, Ann H Klopp, P Andrew Futreal, Cullen M Taniguchi, Kathleen M Schmeler, Lauren E Colbert

Faculty, Staff and Student Publications

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease.

METHODS: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade …

Rare Variant Enrichment Analysis Supports Greb1l As A Contributory Driver Gene In The Etiology Of Mayer-Rokitansky-Küster-Hauser Syndrome, Angad Jolly, Haowei Du, Christelle Borel, Na Chen, Sen Zhao, Christopher M Grochowski, Ruizhi Duan, Jawid M Fatih, Moez Dawood, Sejal Salvi, Shalini N Jhangiani, Donna M Muzny, André Koch, Konstantinos Rouskas, Stavros Glentis, Efthymios Deligeoroglou, Flora Bacopoulou, Carol A Wise, Jennifer E Dietrich, Ignatia B Van Den Veyver, Antigone S Dimas, Sara Brucker, V Reid Sutton, Richard A Gibbs, Stylianos E Antonarakis, Nan Wu, Zeynep H Coban-Akdemir, Lan Zhu, Jennifer E Posey, James R Lupski

Faculty, Staff and Student Publications

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only WNT4 (MIM: 603490) variants have been definitively associated with a subtype of MRKH with hyperandrogenism (MIM: 158330). DNA from 148 clinically diagnosed MRKH probands across 144 unrelated families and available family members from North America, Europe, and South America were exome sequenced (ES) and by family-based genomics analyzed for rare likely deleterious variants. A replication cohort consisting of 442 Han Chinese individuals with MRKH was …

Hsc-Independent Definitive Hematopoiesis Persists Into Adult Life, Michihiro Kobayashi, Haichao Wei, Takashi Yamanashi, Nathalia Azevedo Portilho, Samuel Cornelius, Noemi Valiente, Chika Nishida, Haizi Cheng, Augusto Latorre, W Jim Zheng, Joonsoo Kang, Jun Seita, David J Shih, Jia Qian Wu, Momoko Yoshimoto

Faculty, Staff and Student Publications

It is widely believed that hematopoiesis after birth is established by hematopoietic stem cells (HSCs) in the bone marrow and that HSC-independent hematopoiesis is limited only to primitive erythro-myeloid cells and tissue-resident innate immune cells arising in the embryo. Here, surprisingly, we find that significant percentages of lymphocytes are not derived from HSCs, even in 1-year-old mice. Instead, multiple waves of hematopoiesis occur from embryonic day 7.5 (E7.5) to E11.5 endothelial cells, which simultaneously produce HSCs and lymphoid progenitors that constitute many layers of adaptive T and B lymphocytes in adult mice. Additionally, HSC lineage tracing reveals that the contribution …

School Parent Attitudes And Perceptions Relating To Animals, Animal-Assisted Interventions, And The Support Of Children's Mental Health, Rhoda A Leos, Paula M Cuccaro, John R Herbold, Belinda F Hernandez

Faculty, Staff and Student Publications

Growing awareness of the negative effects of trauma has led San Antonio, TX, school districts to expand efforts that can help mitigate these effects and support mental health. Given the literature around the psychological benefits of human-animal interactions, the concept of incorporating animals in treatments or interventions is not a new one. While schools have begun considering or utilizing animal-assisted interventions (AAIs), there have been limited efforts to understand existing perceptions relating to animals and AAIs among school parents in this Hispanic community. to address this gap, a cross-sectional study consisting of a 34-item survey was conducted to explore attitudes, …

Clinical Outcomes Associated With Npm1 Mutations In Patients With Relapsed Or Refractory Aml, Ghayas C Issa, Aram Bidikian, Sangeetha Venugopal, Marina Konopleva, Courtney D Dinardo, Tapan M Kadia, Gautam Borthakur, Elias Jabbour, Naveen Pemmaraju, Musa Yilmaz, Nicholas J Short, Abhishek Maiti, Koji Sasaki, Lucia Masarova, Sherry Pierce, Koichi Takahashi, Guilin Tang, Sanam Loghavi, Keyur Patel, Michael Andreeff, Kapil Bhalla, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Mutations in Nucleophosmin 1 (NPM1) are associated with a favorable prognosis in newly diagnosed acute myeloid leukemia (AML), however, their prognostic impact in relapsed/refractory (R/R) settings are unknown. In a retrospective analysis, we identified 206 patients (12%) with mutated NPM1 (NPM1c) and compared their outcomes to 1516 patients (88%) with NPM1 wild-type (NPM1wt). NPM1c was associated with higher rates of complete remission or complete remission with incomplete count recovery compared with NPM1wt following each line of salvage therapy (first salvage, 56% vs 37%; P < .0001; second salvage, 33% vs 22%; P = .02; third salvage, 24% vs 14%; P = .02). However, NPM1 mutations had no impact on relapse-free survival (RFS) and overall survival (OS) with each salvage therapy with a median OS following salvage 1, 2 or 3 therapies in NPM1c vs NPM1wt of 7.8 vs 6.0; 5.3 vs 4.1; and 3.5 vs 3.6 months, respectively. Notably, the addition of venetoclax to salvage regimens in patients with NPM1c improved RFS and OS (median RFS, 15.8 vs 4.6 months; P = .05; median OS, 14.7 vs 5.9 months; P = .02). In conclusion, NPM1 mutational status has a minimal impact on prognosis in relapsed or refractory AML; therefore, novel treatment strategies are required to improve outcomes in this entity.

Clinical Features And Shared Mechanisms Of Chronic Gastritis And Osteoporosis, Tao Han, Yili Zhang, Baoyu Qi, Ming Chen, Kai Sun, Xiaokuan Qin, Bowen Yang, He Yin, Aili Xu, Xu Wei, Liguo Zhu

Faculty, Staff and Student Publications

Chronic gastritis (CG) and osteoporosis (OP) are common and occult diseases in the elderly and the relationship of these two diseases have been increasingly exposed. We aimed to explore the clinical characteristics and shared mechanisms of CG patients combined with OP. In the cross-sectional study, all participants were selected from BEYOND study. The CG patients were included and classified into two groups, namely OP group and non-OP group. Univariable and multivariable logistic regression methods were used to evaluate the influencing factors. Furthermore, CG and OP-related genes were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified …

Venetoclax For Acute Myeloid Leukemia In Pediatric Patients: A Texas Medical Center Experience, Adriana Trabal, Amber Gibson, Jiasen He, David Mccall, Michael Roth, Cesar Nuñez, Miriam Garcia, Meredith Buzbee, Laurie Toepfer, Aram Bidikian, Naval Daver, Tapan Kadia, Nicholas J Short, Ghayas C Issa, Farhad Ravandi, Courtney D Dinardo, Guillermo Montalban Bravo, Sofia Garces, Andrea Marcogliese, Hana Paek, Zoann Dreyer, Julienne Brackett, Michele Redell, Joanna Yi, Guillermo Garcia-Manero, Marina Konopleva, Alexandra Stevens, Branko Cuglievan

Faculty, Staff and Student Publications

The BCL-2 inhibitor venetoclax improves survival for adult patients with acute myeloid leukemia (AML) in combination with lower-intensity therapies, but its benefit in pediatric patients with AML remains unclear. We retrospectively reviewed two Texas Medical Center institutions' experience with venetoclax in 43 pediatric patients with AML; median age 17 years (range, 0.6-21). This population was highly refractory; 44% of patients (n = 19) had ≥3 prior lines of therapy, 37% (n = 16) had received a prior bone marrow transplant, and 81% (n = 35) had unfavorable genetics KMT2A (n = 17), WT1 (n = 13), FLT3-ITD (n = 10), …

Single-Center Contemporary Clinical Outcomes After Endovascular Treatment In Patients With De Novo Femoropopliteal Lesions Between 2017 And 2019, Kazunori Horie, Akiko Tanaka, Masataka Taguri, Norio Tada

Faculty, Staff and Student Publications

Background: Drug-coated balloons (DCBs) and drug-eluting stents (DES) were available for treating femoropopliteal disease since 2017 and 2019. However, there are few reports to investigate whether approval of DCB and DES improved primary patency in clinical practice.

Materials and Methods: We divided consecutive 407 patients into 2017 (n=93), 2018 (n=128), and 2019 (n=186) groups, undergoing endovascular therapy (EVT) for de novo femoropopliteal lesions in our hospital. We retrospectively compared clinical characteristics, procedure, and one-year patency between the three groups.

Results: Baseline characteristics were not different except for the lower rate of popliteal lesions in 2017 (p=0.030). Use of DCB increased …

Gingival Transcriptomic Patterns Of Macrophage Polarization During Initiation, Progression, And Resolution Of Periodontitis, Octavio A Gonzalez, Sreenatha S Kirakodu, Linh M Nguyen, Jeffrey L Ebersole

Faculty, Staff and Student Publications

Phenotypic and functional heterogeneity of macrophages is clearly a critical component of their effective functions in innate and adaptive immunity. This investigation hypothesized that altered profiles of gene expression in gingival tissues in health, disease, and resolution would reflect changes in macrophage phenotypes occurring in these tissues. The study used a nonhuman primate model to evaluate gene expression profiles as footprints of macrophage variation using a longitudinal experimental model of ligature-induced periodontitis in animals from 3 to 23 years of age to identify aging effects on the gingival environment. Significant differences were observed in distribution of expressed gene levels for …

Convergent Deployment Of Ancestral Functions During The Evolution Of Mammalian Flight Membranes, Charles Y Feigin, Jorge A Moreno, Raul Ramos, Sarah A Mereby, Ares Alivisatos, Wei Wang, Renée Van Amerongen, Jasmin Camacho, John J Rasweiler, Richard R Behringer, Bruce Ostrow, Maksim V Plikus, Ricardo Mallarino

Faculty, Staff and Student Publications

Lateral flight membranes, or patagia, have evolved repeatedly in diverse mammalian lineages. While little is known about patagium development, its recurrent evolution may suggest a shared molecular basis. By combining transcriptomics, developmental experiments, and mouse transgenics, we demonstrate that lateral Wnt5a expression in the marsupial sugar glider (Petaurus breviceps) promotes the differentiation of its patagium primordium. We further show that this function of Wnt5a reprises ancestral roles in skin morphogenesis predating mammalian flight and has been convergently used during patagium evolution in eutherian bats. Moreover, we find that many genes involved in limb development have been redeployed during …

Cervicovaginal Microbiota Profiles In Precancerous Lesions And Cervical Cancer Among Ethiopian Women, Brhanu Teka, Kyoko Yoshida-Court, Ededia Firdawoke, Zewditu Chanyalew, Muluken Gizaw, Adamu Addissie, Adane Mihret, Lauren E Colbert, Tatiana Cisneros Napravnik, Molly B El Alam, Erica J Lynn, Melissa Mezzari, Jhingran Anuja, Eva Johanna Kantelhardt, Andreas M Kaufmann, Ann H Klopp, Tamrat Abebe

Faculty, Staff and Student Publications

Although high-risk human papillomavirus infection is a well-established risk factor for cervical cancer, other co-factors within the local microenvironment may play an important role in the development of cervical cancer. The current study aimed to characterize the cervicovaginal microbiota in women with premalignant dysplasia or invasive cervical cancer compared with that of healthy women. The study comprised 120 Ethiopian women (60 cervical cancer patients who had not received any treatment, 25 patients with premalignant dysplasia, and 35 healthy women). Cervicovaginal specimens were collected using either an Isohelix DNA buccal swab or an Evalyn brush, and ribosomal RNA sequencing was used …

Health-Related Quality Of Life In Adolescents And Young Adults With Cancer Who Received Radiation Therapy: A Scoping Review, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Lauren M Andring, Yimin Geng, Ramez Kouzy, J Andrew Livingston, Susan K Peterson, Andrew J Bishop, Grace L Smith, Jillian R Gunther, Susan K Parsons, Michael Roth

Faculty, Staff and Student Publications

Purpose: Radiation therapy (RT) is a critical component of treatment for adolescents and young adults (AYAs, age 15-39 years old) diagnosed with cancer. Limited prior studies have focused on AYAs receiving RT despite the potentially burdensome effects of RT. We reviewed the literature to assess health-related quality of life (HRQOL) in AYAs with cancer who received RT.

Methods: The MEDLINE, EMBASE, and Web of Science databases were searched in January 2022 to identify studies that analyzed HRQOL measured by patient-reported outcomes in AYAs who received RT. After title (n = 286) and abstract (n = 58) screening and full-text review …

Aberrant Function Of Pathogenic Stat3 Mutant Proteins Is Linked To Altered Stability Of Monomers And Homodimers, Moses M Kasembeli, Efiyenia Kaparos, Uddalak Bharadwaj, Ahmad Allaw, Alain Khouri, Bianca Acot, David J Tweardy

Faculty, Staff and Student Publications

STAT3 mutations, predominantly in the DNA-binding domain (DBD) and Src-homology 2 domain (SH2D), cause rare cases of immunodeficiency, malignancy, and autoimmunity. The exact mechanisms by which these mutations abrogate or enhance STAT3 function are not completely understood. Here, we examined how loss-of-function (LOF) and gain-of-function (GOF) STAT3 mutations within the DBD and SH2D affect monomer and homodimer protein stability as well as their effect on key STAT3 activation events, including recruitment to phosphotyrosine (pY) sites within peptide hormone receptors, tyrosine phosphorylation at Y705, dimerization, nuclear translocation, and DNA binding. The DBD LOF mutants showed reduced DNA binding when homodimerized, whereas …