Digital Commons Network^™

Prognostic Molecular Biomarkers In Chordomas: A Systematic Review And Identification Of Clinically Usable Biomarker Panels, Franco Rubino, Christopher Alvarez-Breckenridge, Kadir Akdemir, Anthony P Conley, Andrew J Bishop, Wei-Lien Wang, Alexander J Lazar, Laurence D Rhines, Franco Demonte, Shaan M Raza

Faculty, Staff and Student Publications

INTRODUCTION AND OBJECTIVE: Despite the improvements in management and treatment of chordomas over time, the risk of disease recurrence remains high. Consequently, there is a push to develop effective systemic therapeutics for newly diagnosed and recurrent disease. In order to tailor treatment for individual chordoma patients and develop effective surveillance strategies, suitable clinical biomarkers need to be identified. The objective of this study was to systematically review all prognostic biomarkers for chordomas reported to date in order to classify them according to localization, study design and statistical analysis.

METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) …

Testing A Behavioral Activation Gaming App For Depression During Pregnancy: Multimethod Pilot Study, Philipp Karschnia, Jacob S Young, Antonio Dono, Levin Häni, Stephanie T Juenger, Tommaso Sciortino, Francesco Bruno, Nico Teske, Ramin A Morshed, Alexander F Haddad, Yalan Zhang, Sophia Stoecklein, Michael A Vogelbaum, Juergen Beck, Nitin Tandon, Shawn Hervey-Jumper, Annette M Molinaro, Roberta Rudà, Lorenzo Bello, Oliver Schnell, Yoshua Esquenazi, Maximilian I Ruge, Stefan J Grau, Martin Van Den Bent, Michael Weller, Mitchel S Berger, Susan M Chang, Joerg-Christian Tonn

Faculty, Staff and Student Publications

In IDH-wildtype glioblastomas which meet the histopathological or molecular diagnosis criteria, it remains unclear whether the presence of TERT promotor mutations provides additional prognostic information. Based on a multicenter cohort of 466 IDH-wildtype glioblastomas (including 396 with and 70 patients without TERT promotor mutations), we found that TERT promotor mutations were neither associated with progression-free survival nor overall survival. This held true in various treatment-based or molecular subgroups. This argues against standardized analysis for TERT promotor mutation status for the purpose of prognostic or therapeutic relevance in newly diagnosed IDH-wildtype glioblastoma that otherwise meets the histopathological and …

Mucus-Degrading Bacteroides Link Carbapenems To Aggravated Graft-Versus-Host Disease, Eiko Hayase, Tomo Hayase, Mohamed A Jamal, Takahiko Miyama, Chia-Chi Chang, Miriam R Ortega, Saira S Ahmed, Jennifer L Karmouch, Christopher A Sanchez, Alexandria N Brown, Rawan K El-Himri, Ivonne I Flores, Lauren K Mcdaniel, Dung Pham, Taylor Halsey, Annette C Frenk, Valerie A Chapa, Brooke E Heckel, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Lin Tan, Lucas Veillon, Nadim J Ajami, Jennifer A Wargo, Jessica Galloway-Peña, Samuel Shelburne, Roy F Chemaly, Lauren Davey, Robert W P Glowacki, Chen Liu, Gabriela Rondon, Amin M Alousi, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Raphael H Valdivia, Eric C Martens, Philip L Lorenzi, Robert R Jenq

Faculty, Staff and Student Publications

The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic …

Factors Associated With Depression, Anxiety, And Stress Symptoms Among Men In A Rural Area In Vietnam During Covid-19, Van T H Hoang, Ha T H Nguyen

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic has affected health and well-being worldwide, and its psychological effects are receiving substantial attention in the scientific literature. Research to date shows that the pandemic has increased prevalences of depression, anxiety, and stress. This study aimed to estimate the prevalence of mental health symptoms and identify the associated factors among men in a rural area of Vietnam during the COVID-19 pandemic.

METHODS AND FINDINGS: During July 15-31, 2020, we conducted a cross-sectional survey of 1,085 men from 18 years old in 11 rural districts in Thanh Hoa province, Vietnam, and assessed their mental health using the …

Integration Of Mouse Ovary Morphogenesis With Developmental Dynamics Of The Oviduct, Ovarian Ligaments, And Rete Ovarii, Jennifer Mckey, Dilara N Anbarci, Corey Bunce, Alejandra E Ontiveros, Richard R Behringer, Blanche Capel

Faculty, Staff and Student Publications

Morphogenetic events during the development of the fetal ovary are crucial to the establishment of female fertility. However, the effects of structural rearrangements of the ovary and surrounding reproductive tissues on ovary morphogenesis remain largely uncharacterized. Using tissue clearing and lightsheet microscopy, we found that ovary folding correlated with regionalization into cortex and medulla. Relocation of the oviduct to the ventral aspect of the ovary led to ovary encapsulation, and mutual attachment of the ovary and oviduct to the cranial suspensory ligament likely triggered ovary folding. During this process, the rete ovarii (RO) elaborated into a convoluted tubular structure extending …

Molecular Pathways Enhance Drug Response Prediction Using Transfer Learning From Cell Lines To Tumors And Patient-Derived Xenografts, Yi-Ching Tang, Reid T Powell, Assaf Gottlieb

Faculty, Staff and Student Publications

Computational models have been successful in predicting drug sensitivity in cancer cell line data, creating an opportunity to guide precision medicine. However, translating these models to tumors remains challenging. We propose a new transfer learning workflow that transfers drug sensitivity predicting models from large-scale cancer cell lines to both tumors and patient derived xenografts based on molecular pathways derived from genomic features. We further compute feature importance to identify pathways most important to drug response prediction. We obtained good performance on tumors (AUROC = 0.77) and patient derived xenografts from triple negative breast cancers (RMSE = 0.11). Using feature importance, …

A Facile Synthetic Method For Anhydride From Carboxylic Acid With The Promotion Of Triphenylphosphine Oxide And Oxaloyl Chloride, Mengyu Lu, Huihui Fan, Qing Liu, Xiaoling Sun

Faculty, Staff and Student Publications

A highly efficient synthesis reaction of carboxylic anhydrides catalyzed by triphenylphosphine oxide is described for the quick synthesis of a range of symmetric carboxylic anhydrides and cyclic anhydrides under mild and neutral conditions with a high yield. The system adopts the strong reactive intermediate Ph3PCl2 as the catalyst of carboxylic acid salt; driven by catalytic reaction, the synthesis takes a relatively short time to complete.

Functional Determination Of Calcium-Binding Sites Required For The Activation Of Inositol 1,4,5-Trisphosphate Receptors, Vikas Arige, Lara E Terry, Larry E Wagner, Sundeep Malik, Mariah R Baker, Guizhen Fan, Suresh K Joseph, Irina I Serysheva, David I Yule

Faculty, Staff and Student Publications

Inositol 1,4,5-trisphosphate receptors (IP3Rs) initiate a diverse array of physiological responses by carefully orchestrating intracellular calcium (Ca2+) signals in response to various external cues. Notably, IP3R channel activity is determined by several obligatory factors, including IP3, Ca2+, and ATP. The critical basic amino acid residues in the N-terminal IP3-binding core (IBC) region that facilitate IP3 binding are well characterized. In contrast, the residues conferring regulation by Ca2+ have yet to be ascertained. Using comparative structural analysis of Ca2+-binding sites identified in two main families of intracellular Ca2+-release channels, ryanodine receptors (RyRs) and IP3Rs, we identified putative acidic residues coordinating Ca2+ …

Synthesis, Characterization, Antiglycation Evaluation, Molecular Docking, And Admet Studies Of 4-Thiazolidinone Derivatives, Nam Q H Doan, Ngan T K Nguyen, Vu B Duong, Ha T T Nguyen, Long B Vong, Diem N Duong, Nguyet-Thu T Nguyen, Tuyen L T Nguyen, Tuoi T H Do, Tuyen N Truong

Faculty, Staff and Student Publications

Addressing the growing burden of cancer and the shortcomings of chemotherapy in cancer treatment are the current research goals. Research to overcome the limitations of curcumin and to improve its anticancer activity via its heterocycle-fused monocarbonyl analogues (MACs) has immense potential. In this study, 32 asymmetric MACs fused with 1-aryl-1

Impad1 And Syt11 Work In An Epistatic Pathway That Regulates Emt-Mediated Vesicular Trafficking To Drive Lung Cancer Invasion And Metastasis, Rakhee Bajaj, B Leticia Rodriguez, William K Russell, Amanda N Warner, Lixia Diao, Jing Wang, Maria G Raso, Wei Lu, Khaja Khan, Luisa S Solis, Harsh Batra, Ximing Tang, Jared F Fradette, Samrat T Kundu, Don L Gibbons

Faculty, Staff and Student Publications

Lung cancer is a highly aggressive and metastatic disease responsible for approximately 25% of all cancer-related deaths in the United States. Using high-throughput in vitro and in vivo screens, we have previously established Impad1 as a driver of lung cancer invasion and metastasis. Here we elucidate that Impad1 is a direct target of the epithelial microRNAs (miRNAs) miR-200 and miR∼96 and is de-repressed during epithelial-to-mesenchymal transition (EMT); thus, we establish a mode of regulation of the protein. Impad1 modulates Golgi apparatus morphology and vesicular trafficking through its interaction with a trafficking protein, Syt11. These changes in Golgi apparatus dynamics alter …

Tigit Is The Central Player In T-Cell Suppression Associated With Car T-Cell Relapse In Mantle Cell Lymphoma, Vivian Changying Jiang, Dapeng Hao, Preetesh Jain, Yijing Li, Qingsong Cai, Yixin Yao, Lei Nie, Yang Liu, Jingling Jin, Wei Wang, Heng-Huan Lee, Yuxuan Che, Enyu Dai, Guangchun Han, Ruiping Wang, Kunal Rai, Andrew Futreal, Christopher Flowers, Linghua Wang, Michael Wang

Faculty, Staff and Student Publications

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy using brexucabtagene autoleucel (BA) induces remission in many patients with mantle cell lymphoma (MCL), and BA is the only CAR T-cell therapy approved by the FDA for MCL. However, development of relapses to BA is recognized with poor patient outcomes. Multiple CAR T-cell therapies have been approved for other lymphomas and the resistance mechanisms have been investigated. However, the mechanisms underlying BA relapse in MCL have not been investigated and whether any previously reported resistance mechanisms apply to BA-relapsed patients with MCL is unknown.

METHODS: To interrogate BA resistance mechanisms in MCL, we …

Il-6 And Tnf-Α Responses To Acute And Regular Exercise In Adult Individuals With Multiple Sclerosis (Ms): A Systematic Review And Meta-Analysis, Parnian Shobeiri, Homa Seyedmirzaei, Nastaran Karimi, Fatemeh Rashidi, Antônio L Teixeira, Serge Brand, Dena Sadeghi-Bahmani, Nima Rezaei

Faculty, Staff and Student Publications

Background: In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of the possible protection of physical activity against disease progression in multiple sclerosis (MS). However, the question arises if acute or regular exercise has any impact on the immune system in PwMS. To answer this question, we performed a systematic review and meta-analysis on both plasma and serum cytokine levels (IL-6 and TNF-α) before and after acute and regular exercise among PwMS and compared to healthy controls.

Method: We performed an online search via PubMed, EMBASE, …

Nasal Nitric Oxide Levels: Improving The Diagnosis Of Primary Ciliary Dyskinesia In Puerto Rico, Wilfredo De Jesús-Rojas, Francisco Alvarado-Huerta, Jesús M Meléndez-Montañez, José Muñiz-Hernández, Arnaldo Santos-López, Ricardo A Mosquera

Faculty, Staff and Student Publications

Primary Ciliary Dyskinesia (PCD) is a rare genetic disease characterized by motile cilia dysfunction with a prevalence of 1 in 16,309 individuals in Hispanic populations. In Puerto Rico, the prevalence of PCD is unknown. Diagnosis of PCD in Puerto Rico is challenging due to the lack of diagnostic technology. Algorithms for PCD diagnosis include clinical history, genetic testing, ciliary biopsy, and nasal Nitric Oxide (nNO) levels. For the first time, this study successfully implemented and measured the nNO levels in subjects with the RSPH4A (c.921+3_921+6del (intronic)) as a diagnostic tool to complement the current algorithm for PCD diagnosis on the …

Effect Of Al2o3 On Nanostructure And Ion Transport Properties Of Pva/Peg/Ssa Polymer Electrolyte Membrane, Hamdy F M Mohamed, Esam E Abdel-Hady, Mostafa M Y Abdel-Moneim, Mohamed A M Bakr, Mohamed A M Soliman, Mahmoud G H Shehata, Mahmoud A T Ismail

Faculty, Staff and Student Publications

Polymer electrolyte membrane (PEM) fuel cells have the potential to reduce our energy consumption, pollutant emissions, and dependence on fossil fuels. To achieve a wide range of commercial PEMs, many efforts have been made to create novel polymer-based materials that can transport protons under anhydrous conditions. In this study, cross-linked poly(vinyl) alcohol (PVA)/poly(ethylene) glycol (PEG) membranes with varying alumina (Al2O3) content were synthesized using the solvent solution method. Wide-angle X-ray diffraction (XRD), water uptake, ion exchange capacity (IEC), and proton conductivity were then used to characterize the membranes. XRD results showed that the concentration of Al2O3 affected the degree of …

Genetic Variations Mir-10aa>T, Mir-30ca>G, Mir-181at>C, And Mir-499ba>G And The Risk Of Recurrent Pregnancy Loss In Korean Women, Hui-Jeong An, Sung-Hwan Cho, Han-Sung Park, Ji-Hyang Kim, Young-Ran Kim, Woo-Sik Lee, Jung-Ryeol Lee, Seong-Soo Joo, Eun-Hee Ahn, Nam-Keun Kim

Faculty, Staff and Student Publications

This study investigated the genetic association between recurrent pregnancy loss (RPL) and microRNA (miRNA) polymorphisms in miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G in Korean women. Blood samples were collected from 381 RPL patients and 281 control participants, and genotyping of miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G was carried out by TaqMan miRNA RT-Real Time polymerase chain reaction (PCR). Four polymorphisms were identified, including miR-10aA>T, miR-30cA>G, miR-181aT>C, and miR-499bA>G. MiR-10a dominant model (AA vs. AT + TT) and miR-499bGG genotypes were associated with increased RPL risk (adjusted odds ratio [AOR] = …

Analysis Of The Efficacy Of Autologous Peripheral Blood Stem Cell Transplantation In High-Risk Neuroblastoma, Jin Yan, Li Jie, Yang Jiaxing, Cao Yanna, Li Zhanglin, Li Zhongyuan, Wang Daowei, Zhao Guangzong, Zhong Benfu, Yan Jie, Zhao Qiang

Faculty, Staff and Student Publications

Objective: This study aimed to analyze the efficacy of autologous peripheral blood stem cell transplantation for high-risk neuroblastoma in China.

Methods: The data of 90 high-risk neuroblastoma patients treated with the CCCG-NB 2015 regimen were reviewed. The baseline clinicopathological characteristics and prognosis were analyzed and compared. In addition, the prognoses of tandem autologous stem cell transplantation and single autologous stem cell transplantation groups were compared.

Results: The results of survival analysis showed that autologous peripheral blood stem cell transplantation based on this pretreatment regimen significantly improved the prognosis of children in the high-risk group. The 3-year event-free survival (EFS) and …

Temporal Lobe White Matter Asymmetry And Language Laterality In Epilepsy Patients, Nikolaos Soldatos, Huy Pham, Walid D Fakhouri, Binh Ngo, Panagiotis Lampropoulos, Tiffany Tran, Robin Weltman

Faculty, Staff and Student Publications

(1) Background: Several studies showed a sustained temperature of 47 °C or 50 °C for one minute resulted in vascular stasis and bone resorption with only limited bone regrowth over a 3–4-week healing period. The purpose of the present study was to evaluate the temperature changes (ΔΤ) that occur during the preparation of dental implant osteotomies using MIS® straight drills versus Densah® burs in a clockwise (cutting) drilling protocol. (2) Methods: Two hundred forty (240) osteotomies of two different systems’ drills were prepared at 6 mm depth at 800, 1000, and 1200 revolutions per minute (RPM), in fresh, unembalmed tibiae, …

To Bind Or Not To Bind: Cistromic Reprogramming In Prostate Cancer, Michelle Shen, Léa-Kristine Demers, Swneke D Bailey, David P Labbé

Faculty, Staff and Student Publications

The term "cistrome" refers to the genome-wide location of regulatory elements associated with transcription factor binding-sites. The cistrome of key regulatory factors in prostate cancer etiology are substantially reprogrammed and altered during prostatic transformation and disease progression. For instance, the cistrome of the androgen receptor (AR), a ligand-inducible transcription factor central in normal prostate epithelium biology, is directly impacted and substantially reprogrammed during malignant transformation. Accumulating evidence demonstrates that additional transcription factors that are frequently mutated, or aberrantly expressed in prostate cancer, such as the pioneer transcription factors Forkhead Box A1 (FOXA1), the homeobox protein HOXB13, and the GATA binding …

Engineering Sars-Cov-2 Specific Cocktail Antibodies Into A Bispecific Format Improves Neutralizing Potency And Breadth, Zhiqiang Ku, Xuping Xie, Jianqing Lin, Peng Gao, Bin Wu, Abbas El Sahili, Hang Su, Yang Liu, Xiaohua Ye, Eddie Yongjun Tan, Xin Li, Xuejun Fan, Boon Chong Goh, Wei Xiong, Hannah Boyd, Antonio E Muruato, Hui Deng, Hongjie Xia, Jing Zou, Birte K Kalveram, Vineet D Menachery, Ningyan Zhang, Julien Lescar, Pei-Yong Shi, Zhiqiang An

Faculty, Staff and Student Publications

One major limitation of neutralizing antibody-based COVID-19 therapy is the requirement of costly cocktails to reduce emergence of antibody resistance. Here we engineer two bispecific antibodies (bsAbs) using distinct designs and compared them with parental antibodies and their cocktail. Single molecules of both bsAbs block the two epitopes targeted by parental antibodies on the receptor-binding domain (RBD). However, bsAb with the IgG-(scFv)2 design (14-H-06) but not the CrossMAb design (14-crs-06) shows increased antigen-binding and virus-neutralizing activities against multiple SARS-CoV-2 variants as well as increased breadth of neutralizing activity compared to the cocktail. X-ray crystallography and cryo-EM reveal distinct binding models …

Regional Variation In Brain Tissue Texture In Patients With Tonic-Clonic Seizures, Jennifer A Ogren, Luke A Allen, Bhaswati Roy, Beate Diehl, John M Stern, Dawn S Eliashiv, Samden D Lhatoo, Ronald M Harper, Rajesh Kumar

Faculty, Staff and Student Publications

Patients with epilepsy, who later succumb to sudden unexpected death, show altered brain tissue volumes in selected regions. It is unclear whether the alterations in brain tissue volume represent changes in neurons or glial properties, since volumetric procedures have limited sensitivity to assess the source of volume changes (e.g., neuronal loss or glial cell swelling). We assessed a measure, entropy, which can determine tissue homogeneity by evaluating tissue randomness, and thus, shows tissue integrity; the measure is easily calculated from T1-weighted images. T1-weighted images were collected with a 3.0-Tesla MRI from 53 patients with tonic-clonic (TC) …

Kat-Arc Accelerated 4d Flow Cmr: Clinical Validation For Transvalvular Flow And Peak Velocity Assessment, Hosamadin Assadi, Bhalraam Uthayachandran, Rui Li, James Wardley, Tha H Nyi, Ciaran Grafton-Clarke, Andrew J Swift, Ana Beatriz Solana, Jean-Paul Aben, Kurian Thampi, David Hewson, Chris Sawh, Richard Greenwood, Marina Hughes, Bahman Kasmai, Liang Zhong, Marcus Flather, Vassilios S Vassiliou, Pankaj Garg

Faculty, Staff and Student Publications

BACKGROUND: To validate the k-adaptive-t autocalibrating reconstruction for Cartesian sampling (kat-ARC), an exclusive sparse reconstruction technique for four-dimensional (4D) flow cardiac magnetic resonance (CMR) using conservation of mass principle applied to transvalvular flow.

METHODS: This observational retrospective study (2020/21-075) was approved by the local ethics committee at the University of East Anglia. Consent was waived. Thirty-five patients who had a clinical CMR scan were included. CMR protocol included cine and 4D flow using Kat-ARC acceleration factor 6. No respiratory navigation was applied. For validation, the agreement between mitral net flow (MNF) and the aortic net flow (ANF) was investigated. Additionally, …

Therapeutic Management Of Chronic Lymphocytic Leukemia Presenting With Recurrent Massive Ascites, Ugochi Ebinama, Nathaniel R Wilson, Anindita Ghosh, Binsah S George

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy that is categorized by the production and accumulation of CD5+ monoclonal B cell lymphocytes, commonly in the spleen, bone marrow, and peripheral blood; these are morphologically mature lymphocytes with abnormal immune function. Ascites, although common in solid organ malignancies such as ovarian, breast, and gastrointestinal, is a rare clinical manifestation in hematological malignancies. The case presented herein describes an elderly male patient with CLL who presented with transudative ascites 7 years after the completion of chemotherapy. Microscopic analysis and flow cytometry of the patient's ascitic fluid were consistent with CLL, and he …

Gastrointestinal Microbiome Disruption And Antibiotic-Associated Diarrhea In Children Receiving Antibiotic Therapy For Community-Acquired Pneumonia, Jiye Kwon, Yong Kong, Martina Wade, Derek J Williams, Clarence Buddy Creech, Scott Evans, Emmanuel B Walter, Judy M Martin, Jeffrey S Gerber, Jason G Newland, Meghan E Hofto, Mary Allen Staat, Henry F Chambers, Vance G Fowler, W Charles Huskins, Melinda M Pettigrew

Faculty, Staff and Student Publications

Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotics. We examined the gastrointestinal microbiota in children treated with β-lactams for community-acquired pneumonia. Data were from 66 children (n = 198 samples), aged 6-71 months, enrolled in the SCOUT-CAP trial (NCT02891915). AAD was defined as ≥1 day of diarrhea. Stool samples were collected on study days 1, 6-10, and 19-25. Samples were analyzed using 16S ribosomal RNA gene sequencing to identify associations between patient characteristics, microbiota characteristics, and AAD (yes/no). Nineteen (29%) children developed AAD. Microbiota compositional profiles differed between AAD groups (permutational multivariate analysis of variance, P < .03) and across visits (P < .001). Children with higher baseline relative abundances of 2 Bacteroides species were less likely to experience AAD. Higher baseline abundance of Lachnospiraceae and amino acid biosynthesis pathways were associated with AAD. Children in the AAD group experienced prolonged dysbiosis (P < .05). Specific gastrointestinal microbiota profiles are associated with AAD in children.

Insular Cortical Circuits As An Executive Gateway To Decipher Threat Or Extinction Memory Via Distinct Subcortical Pathways, Qi Wang, Jia-Jie Zhu, Lizhao Wang, Yan-Peng Kan, Yan-Mei Liu, Yan-Jiao Wu, Xue Gu, Xin Yi, Ze-Jie Lin, Qin Wang, Jian-Fei Lu, Qin Jiang, Ying Li, Ming-Gang Liu, Nan-Jie Xu, Michael X Zhu, Lu-Yang Wang, Siyu Zhang, Wei-Guang Li, Tian-Le Xu

Faculty, Staff and Student Publications

Threat and extinction memories are crucial for organisms' survival in changing environments. These memories are believed to be encoded by separate ensembles of neurons in the brain, but their whereabouts remain elusive. Using an auditory fear-conditioning and extinction paradigm in male mice, here we discovered that two distinct projection neuron subpopulations in physical proximity within the insular cortex (IC), targeting the central amygdala (CeA) and nucleus accumbens (NAc), respectively, to encode fear and extinction memories. Reciprocal intracortical inhibition of these two IC subpopulations gates the emergence of either fear or extinction memory. Using rabies-virus-assisted tracing, we found IC-NAc projection neurons …

The Age-Dependent Immune Response To Ischemic Stroke, Marissa M Shams-White, Ashley H Tjaden, Sharon L Edelstein, Sarah Bassiouni, Lisa L Kahle, Catherine Kim, Xavier Pi-Sunyer, Karla A Temple, Elizabeth M Venditti, Jill Reedy, Brandy M Heckman-Stoddard

Faculty, Staff and Student Publications

BACKGROUND: The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) 3rd expert report highlights up-to-date Cancer Prevention Recommendations that may reduce burdens of many chronic diseases, including diabetes. This study examined if following a lifestyle that aligns with the recommendations - assessed via the 2018 WCRF/AICR Score - was associated with lower risk of type 2 diabetes in high-risk adults participating in the Diabetes Prevention Program Outcomes Study (DPPOS).

METHODS: The Diabetes Prevention Program (DPP) randomized adults at high risk for diabetes to receive a lifestyle intervention (ILS), metformin (MET) or a placebo (PLB) (mean: 3.2 years), with …

Invasive Group A Streptococcal Penicillin Binding Protein 2× Variants Associated With Reduced Susceptibility To Β-Lactam Antibiotics In The United States, 2015-2021, Sopio Chochua, Benjamin Metcalf, Zhongya Li, Saundra Mathis, Theresa Tran, Joy Rivers, Katherine E Fleming-Dutra, Yuan Li, Lesley Mcgee, Bernard Beall

Faculty, Staff and Student Publications

All known group A streptococci [GAS] are susceptible to β-lactam antibiotics. We recently identified an invasive GAS (iGAS) variant (emm43.4/PBP2x-T553K) with unusually high minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin, although clinically susceptible to β-lactams. We aimed to quantitate PBP2x variants, small changes in β-lactam MICs, and lineages within contemporary population-based iGAS. PBP2x substitutions were comprehensively identified among 13,727 iGAS recovered during 2015-2021, in the USA. Isolates were subjected to antimicrobial susceptibility testing employing low range agar diffusion and PBP2x variants were subjected to phylogenetic analyses. Fifty-five variants were defined based upon substitutions within an assigned PBP2x …

Amino Acids, Microbiota-Related Metabolites, And The Risk Of Incident Diabetes Among Normoglycemic Chinese Adults: Findings From The 4c Study, Shuangyuan Wang, Mian Li, Hong Lin, Guixia Wang, Yu Xu, Xinjie Zhao, Chunyan Hu, Yi Zhang, Ruizhi Zheng, Ruying Hu, Lixin Shi, Rui Du, Qing Su, Jiqiu Wang, Yuhong Chen, Xuefeng Yu, Li Yan, Tiange Wang, Zhiyun Zhao, Ruixin Liu, Xiaolin Wang, Qi Li, Guijun Qin, Qin Wan, Gang Chen, Min Xu, Meng Dai, Di Zhang, Xulei Tang, Zhengnan Gao, Feixia Shen, Zuojie Luo, Yingfen Qin, Li Chen, Yanan Huo, Qiang Li, Zhen Ye, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Shenghan Lai, Yiming Mu, Lulu Chen, Donghui Li, Guowang Xu, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu

Faculty, Staff and Student Publications

Although previous studies suggest that amino acids (AAs) and microbiota-related metabolites (MRMs) are associated with type 2 diabetes mellitus (T2DM), the results remain unclear among normoglycemic populations. We test 28 serum AAs and 22 MRMs in 3,414 subjects with incident diabetes and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. In fully adjusted logistic regression models, per SD increment of branched-chain AAs, aromatic AAs, asparagine, alanine, glutamic acid, homoserine, 2-aminoadipic acid, histidine, methionine, and proline are positively associated with incident T2DM. In the MRM panel, serum carnitines, N-acetyltryptophan, and uric acid are positively associated with …

Overlapping And Distinct Functions Of The Paralogous Pagr Regulators Of Bacillus Anthracis, Ileana D Corsi, Theresa M Koehler

Faculty, Staff and Student Publications

The Bacillus anthracis pagA gene, encoding the protective antigen component of anthrax toxin, is part of a bicistronic operon on pXO1 that codes for its own repressor, PagR1. In addition to the pagAR1 operon, PagR1 regulates sap and eag, two chromosome genes encoding components of the surface layer, a mounting structure for surface proteins involved in virulence. Genomic studies have revealed a PagR1 paralog, PagR2, encoded by a gene on pXO2. The amino acid sequences of the paralogues are 71% identical and show similarity to the ArsR family of transcription regulators. We determined that the expression of either rPagR1 …

Overlapping And Distinct Functions Of The Paralogous Pagr Regulators Of Bacillus Anthracis, Ileana D Corsi, Theresa M Koehler

Faculty, Staff and Student Publications

The Bacillus anthracis pagA gene, encoding the protective antigen component of anthrax toxin, is part of a bicistronic operon on pXO1 that codes for its own repressor, PagR1. In addition to the pagAR1 operon, PagR1 regulates sap and eag, two chromosome genes encoding components of the surface layer, a mounting structure for surface proteins involved in virulence. Genomic studies have revealed a PagR1 paralog, PagR2, encoded by a gene on pXO2. The amino acid sequences of the paralogues are 71% identical and show similarity to the ArsR family of transcription regulators. We determined that the expression of either rPagR1 …

Effect Of Roflumilast Cream Vs Vehicle Cream On Chronic Plaque Psoriasis: The Dermis-1 And Dermis-2 Randomized Clinical Trials, Mark G Lebwohl, Leon H Kircik, Angela Y Moore, Linda Stein Gold, Zoe D Draelos, Melinda J Gooderham, Kim A Papp, Jerry Bagel, Neal Bhatia, James Q Del Rosso, Laura K Ferris, Lawrence J Green, Adelaide A Hebert, Terry Jones, Steven E Kempers, David M Pariser, Paul S Yamauchi, Matthew Zirwas, Lorne Albrecht, Alim R Devani, Mark Lomaga, Amy Feng, Scott Snyder, Patrick Burnett, Robert C Higham, David R Berk

Faculty, Staff and Student Publications

IMPORTANCE: Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis.

OBJECTIVE: To evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis.

DESIGN, SETTING, AND PARTICIPANTS: Two phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n = 439] and DERMIS-2 [trial 2; n = 442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between …