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Mir-9-1 Suppresses Cell Proliferation And Promotes Apoptosis By Targeting Uhrf1 In Lung Cancer, Cheng-You Jia, Wei Xiang, Ji-Bin Liu, Geng-Xi Jiang, Feng Sun, Jian-Jun Wu, Xiao-Li Yang, Rui Xin, Yi Shi, Dan-Dan Zhang, Wen Li, Zavuga Zuberi, Jie Zhang, Gai-Xia Lu, Hui-Min Wang, Pei-Yao Wang, Fei Yu, Zhong-Wei Lv, Yu-Shui Ma, Da Fu Jan 2021

Mir-9-1 Suppresses Cell Proliferation And Promotes Apoptosis By Targeting Uhrf1 In Lung Cancer, Cheng-You Jia, Wei Xiang, Ji-Bin Liu, Geng-Xi Jiang, Feng Sun, Jian-Jun Wu, Xiao-Li Yang, Rui Xin, Yi Shi, Dan-Dan Zhang, Wen Li, Zavuga Zuberi, Jie Zhang, Gai-Xia Lu, Hui-Min Wang, Pei-Yao Wang, Fei Yu, Zhong-Wei Lv, Yu-Shui Ma, Da Fu

Faculty, Staff and Student Publications

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 …


Risk Factors For Amyotrophic Lateral Sclerosis: A Regional United States Case-Control Study., Angeline S Andrew, Walter G Bradley, Daniel Peipert, Tanya Butt, Kwadwo Amoako, Erik P Pioro, Rup Tandan, John Novak, Adam Quick, K Doug Pugar, Komal Sawlani, Bashar Katirji, Todd A Hayes, Pamela Cazzolli, Jiang Gui, Paul Mehta, D Kevin Horton, Elijah W Stommel Jan 2021

Risk Factors For Amyotrophic Lateral Sclerosis: A Regional United States Case-Control Study., Angeline S Andrew, Walter G Bradley, Daniel Peipert, Tanya Butt, Kwadwo Amoako, Erik P Pioro, Rup Tandan, John Novak, Adam Quick, K Doug Pugar, Komal Sawlani, Bashar Katirji, Todd A Hayes, Pamela Cazzolli, Jiang Gui, Paul Mehta, D Kevin Horton, Elijah W Stommel

Ambulatory and Primary Care Articles

Most amyotrophic lateral sclerosis (ALS) cases are considered sporadic, without a known genetic basis, and environmental exposures are thought to play a causal role. To learn more about sporadic ALS etiology, we recruited n = 188 ALS patients from northern New England and Ohio and matched controls 2:1 from the general population of the same regions. Questionnaires evaluated the association between a variety of lifestyle, behavioral (ie, hobbies and activities), and occupational factors and the risk of ALS, including the duration of time between exposure and ALS onset, and exposure frequency. Head trauma was associated with increased ALS risk (adjusted …


Acute Symptoms Of Mild To Moderate Covid-19 Are Highly Heterogeneous Across Individuals And Over Time, Thomas L. Rodebaugh, Madelyn R. Frumkin, Angela M. Reiersen, Eric J. Lenze, Michael S. Avidan, J. Philip Miller, Jay F. Piccirillo, Charles F. Zorumski, Caline Mattar Jan 2021

Acute Symptoms Of Mild To Moderate Covid-19 Are Highly Heterogeneous Across Individuals And Over Time, Thomas L. Rodebaugh, Madelyn R. Frumkin, Angela M. Reiersen, Eric J. Lenze, Michael S. Avidan, J. Philip Miller, Jay F. Piccirillo, Charles F. Zorumski, Caline Mattar

Open Access Publications

Background: The symptoms of coronavirus disease 2019 (COVID-19) appear to be heterogenous, and the typical course of these symptoms is unknown. Our objectives were to characterize the common trajectories of COVID-19 symptoms and to assess how symptom course predicts other symptom changes as well as clinical deterioration.

Methods: One hundred sixty-two participants with acute COVID-19 responded to surveys up to 31 times for up to 17 days. Several statistical methods were used to characterize the temporal dynamics of these symptoms. Because 9 participants showed clinical deterioration, we explored whether these participants showed any differences in symptom profiles.

Results: Trajectories varied …


Overlapping But Disparate Inflammatory And Immunosuppressive Responses To Sars-Cov-2 And Bacterial Sepsis: An Immunological Time Course Analysis, Tyler J Loftus, Ricardo Ungaro, Marvin Dirain, Philip A Efron, Monty B Mazer, Kenneth E Remy, Richard S Hotchkiss, Luer Zhong, Rhonda Bacher, Petr Starostik, Lyle L Moldawer, Scott C Brakenridge Jan 2021

Overlapping But Disparate Inflammatory And Immunosuppressive Responses To Sars-Cov-2 And Bacterial Sepsis: An Immunological Time Course Analysis, Tyler J Loftus, Ricardo Ungaro, Marvin Dirain, Philip A Efron, Monty B Mazer, Kenneth E Remy, Richard S Hotchkiss, Luer Zhong, Rhonda Bacher, Petr Starostik, Lyle L Moldawer, Scott C Brakenridge

Open Access Publications

Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia and propensity for secondary infections. The nature of the immunological dyscrasias for these differing etiologies and their time course remain unclear. In this study, thirty hospitalized patients with SARS-CoV-2 infection were compared with ten critically ill patients with bacterial sepsis over 21 days, as well as ten healthy control subjects. Blood was sampled between days 1 and 21 after admission for targeted plasma biomarker analysis, cellular phenotyping, and leukocyte functional analysis


Assessment Of The Gut Bacterial Microbiome And Metabolome Of Girls And Women With Rett Syndrome, Santosh Thapa, Alamelu Venkatachalam, Nabeel Khan, Mohammed Naqvi, Miriam Balderas, Jessica K Runge, Anthony Haag, Kathleen M Hoch, Daniel G Glaze, Ruth Ann Luna, Kathleen J Motil Jan 2021

Assessment Of The Gut Bacterial Microbiome And Metabolome Of Girls And Women With Rett Syndrome, Santosh Thapa, Alamelu Venkatachalam, Nabeel Khan, Mohammed Naqvi, Miriam Balderas, Jessica K Runge, Anthony Haag, Kathleen M Hoch, Daniel G Glaze, Ruth Ann Luna, Kathleen J Motil

Children’s Nutrition Research Center Staff Publications

Background: Gastrointestinal problems affect the health and quality of life of individuals with Rett syndrome (RTT) and pose a medical hardship for their caregivers. We hypothesized that the variability in the RTT phenotype contributes to the dysbiosis of the gut microbiome and metabolome in RTT, predisposing these individuals to gastrointestinal dysfunction.

Objectives: We characterized the gut bacterial microbiome and metabolome in girls and young women with RTT (n = 44) and unaffected controls (n = 21), and examined the relation between the composition of the microbiome and variations in the RTT phenotype.

Methods: Demographics and clinical information, including growth and …


Multiomics Characterization Of Preterm Birth In Low- And Middle-Income Countries., Fyezah Jehan, Sunil Sazawal, Abdullah H. Baqui, Muhammad Imran Nisar, Usha Dhingra, Rasheda Khanam, Muhammad Ilyas, Arup Dutta, Dipak K. Mitra, Usma Mehmood, Saikat Deb, Arif Mahmud, Aneeta Hotwani, Said Mohammed Ali, Sayedur Rahman, Ambreen Nizar, Shaali Makame Ame, Mamun Ibne Moin, Sajid Muhammad, Aishwarya Chauhan, Nazma Begum, Waqasuddin Khan, Sayan Das, Salahuddin Ahmed, Tarik Hasan, Javairia Khalid, Syed Jafar Raza Rizvi, Mohammed Hamad Juma, Nabidul Haque Chowdhury, Furqan Kabir, Fahad Aftab, Abdul Quaiyum, Alexander Manu, Sachiyo Yoshida, Rajiv Bahl, Anisur Rahman, Jesmin Pervin, Jennifer Winston, Patrick Musonda, Jeffrey S. A. Stringer, James A. Litch, Mohammad Sajjad Ghaemi, Mira N. Moufarrej, Kévin Contrepois, Songjie Chen, Ina A. Stelzer, Natalie Stanley, Alan L. Chang, Ghaith Bany Hammad, Ronald J. Wong, Candace Liu, Cecele C. Quaintance, Anthony Culos, Camilo Espinosa, Maria Xenochristou, Martin Becker, Ramin Fallahzadeh, Edward Ganio, Amy S. Tsai, Dyani Gaudilliere, Eileen S. Tsai, Xiaoyuan Han, Kazuo Ando, Martha Tingle, Ivana Maric, Paul H. Wise, Virginia D. Winn, Maurice L. Druzin, Ronald S. Gibbs, Gary L. Darmstadt, Jeffrey C. Murray, Gary M. Shaw, David K. Stevenson, Michael P. Snyder, Stephen R. Quake, Martin S. Angst, Brice Gaudilliere, Nima Aghaeepour Dec 2020

Multiomics Characterization Of Preterm Birth In Low- And Middle-Income Countries., Fyezah Jehan, Sunil Sazawal, Abdullah H. Baqui, Muhammad Imran Nisar, Usha Dhingra, Rasheda Khanam, Muhammad Ilyas, Arup Dutta, Dipak K. Mitra, Usma Mehmood, Saikat Deb, Arif Mahmud, Aneeta Hotwani, Said Mohammed Ali, Sayedur Rahman, Ambreen Nizar, Shaali Makame Ame, Mamun Ibne Moin, Sajid Muhammad, Aishwarya Chauhan, Nazma Begum, Waqasuddin Khan, Sayan Das, Salahuddin Ahmed, Tarik Hasan, Javairia Khalid, Syed Jafar Raza Rizvi, Mohammed Hamad Juma, Nabidul Haque Chowdhury, Furqan Kabir, Fahad Aftab, Abdul Quaiyum, Alexander Manu, Sachiyo Yoshida, Rajiv Bahl, Anisur Rahman, Jesmin Pervin, Jennifer Winston, Patrick Musonda, Jeffrey S. A. Stringer, James A. Litch, Mohammad Sajjad Ghaemi, Mira N. Moufarrej, Kévin Contrepois, Songjie Chen, Ina A. Stelzer, Natalie Stanley, Alan L. Chang, Ghaith Bany Hammad, Ronald J. Wong, Candace Liu, Cecele C. Quaintance, Anthony Culos, Camilo Espinosa, Maria Xenochristou, Martin Becker, Ramin Fallahzadeh, Edward Ganio, Amy S. Tsai, Dyani Gaudilliere, Eileen S. Tsai, Xiaoyuan Han, Kazuo Ando, Martha Tingle, Ivana Maric, Paul H. Wise, Virginia D. Winn, Maurice L. Druzin, Ronald S. Gibbs, Gary L. Darmstadt, Jeffrey C. Murray, Gary M. Shaw, David K. Stevenson, Michael P. Snyder, Stephen R. Quake, Martin S. Angst, Brice Gaudilliere, Nima Aghaeepour

All Dugoni School of Dentistry Faculty Articles

Importance: Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies.

Objective: To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB.

Design, Setting, and Participants: This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in …


Digital Image Analysis For The Detection Of Group B Streptococcus From Chromid Strepto B Medium Using Phenomatrix Algorithms, Justin Baker, Karen Timm, Matthew Faron, Nathan Ledeboer, Karissa Culbreath Dec 2020

Digital Image Analysis For The Detection Of Group B Streptococcus From Chromid Strepto B Medium Using Phenomatrix Algorithms, Justin Baker, Karen Timm, Matthew Faron, Nathan Ledeboer, Karissa Culbreath

Pathology Research and Scholarship

Group B Streptococcus (GBS) can be found to colonize about 25% of all healthy, adult women and is the leading infectious cause of early neonatal morbidity and mortality in the United States. This study evaluated the clinical performance of PhenoMatrix (PM) chromogenic detection module (CDM) digital imaging software in detection of GBS from LIM broth plated on ChromID Strepto B chromogenic medium (ChromID) using the WASP automated processor. The performance of the PM CDM was compared to manual culture review of the digital images and molecular detection of GBS. ChromID alone had a sensitivity and specificity of 84.5% and 94.7%, …


Patient Factors Influencing Acute Gluten Reactions And Cytokine Release In Treated Coeliac Disease., Jason A Tye-Din, A James M Daveson, Kaela E Goldstein, Holly L Hand, Kristin M Neff, Gautam Goel, Leslie J Williams, Kenneth E Truitt, Robert P Anderson, Anthony Dimariono (Reset Ced Study Group) Nov 2020

Patient Factors Influencing Acute Gluten Reactions And Cytokine Release In Treated Coeliac Disease., Jason A Tye-Din, A James M Daveson, Kaela E Goldstein, Holly L Hand, Kristin M Neff, Gautam Goel, Leslie J Williams, Kenneth E Truitt, Robert P Anderson, Anthony Dimariono (Reset Ced Study Group)

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Patients with coeliac disease (CD) commonly report a variety of adverse symptoms to gluten, but descriptions of the symptomatic response in the literature may have been confounded by the presence of food components such as fermentable carbohydrates (FODMAPs) causing symptoms of irritable bowel syndrome independent of gluten. In recent unmasked and masked low FODMAP gluten challenge studies in small groups of treated CD patients, nausea and vomiting were shown to be the key symptoms associated with serum interleukin (IL)-2 release. Our objective was to utilise a large and diverse cohort of people with CD undertaking a standardised gluten food …


Impact Of Diabetes On The Gut And Salivary Iga Microbiomes, Eric L Brown, Heather T Essigmann, Kristi L Hoffman, Noah W Palm, Sarah M Gunter, Joel M Sederstrom, Joseph F Petrosino, Goo Jun, David Aguilar, William B Perkison, Craig L Hanis, Herbert L Dupont Nov 2020

Impact Of Diabetes On The Gut And Salivary Iga Microbiomes, Eric L Brown, Heather T Essigmann, Kristi L Hoffman, Noah W Palm, Sarah M Gunter, Joel M Sederstrom, Joseph F Petrosino, Goo Jun, David Aguilar, William B Perkison, Craig L Hanis, Herbert L Dupont

Faculty, Staff and Student Publications

Mucosal surfaces like those present in the lung, gut, and mouth interface with distinct external environments. These mucosal gateways are not only portals of entry for potential pathogens but also homes to microbial communities that impact host health. Secretory immunoglobulin A (SIgA) is the single most abundant acquired immune component secreted onto mucosal surfaces and, via the process of immune exclusion, shapes the architecture of these microbiomes. Not all microorganisms at mucosal surfaces are targeted by SIgA; therefore, a better understanding of the SIgA-coated fraction may identify the microbial constituents that stimulate host immune responses in the context of health …


Genetics And Geography Of Leukocyte Telomere Length In Sub-Saharan Africans, Steven C Hunt, Michael A Province, Et Al. Nov 2020

Genetics And Geography Of Leukocyte Telomere Length In Sub-Saharan Africans, Steven C Hunt, Michael A Province, Et Al.

2020-Current year OA Pubs

Leukocyte telomere length (LTL) might be causal in cardiovascular disease and major cancers. To elucidate the roles of genetics and geography in LTL variability across humans, we compared LTL measured in 1295 sub-Saharan Africans (SSAs) with 559 African-Americans (AAms) and 2464 European-Americans (EAms). LTL differed significantly across SSAs (P = 0.003), with the San from Botswana (with the oldest genomic ancestry) having the longest LTL and populations from Ethiopia having the shortest LTL. SSAs had significantly longer LTL than AAms [P = 6.5(e-16)] whose LTL was significantly longer than EAms [P = 2.5(e-7)]. Genetic variation in SSAs explained 52% of …


Genetics Of Smoking Behaviors In American Indians, Jeffrey A Henderson, Dedra S Buchwald, Barbara V Howard, Patricia Nez Henderson, Yafang Li, Rachel F Tyndale, Christopher I Amos, Olga Y Gorlova, Collaborative To Improve Native Cancer Outcomes (Cinco), A P50 Center For Population Health And Health Disparities Program Project Sponsored By The National Cancer Institute Nov 2020

Genetics Of Smoking Behaviors In American Indians, Jeffrey A Henderson, Dedra S Buchwald, Barbara V Howard, Patricia Nez Henderson, Yafang Li, Rachel F Tyndale, Christopher I Amos, Olga Y Gorlova, Collaborative To Improve Native Cancer Outcomes (Cinco), A P50 Center For Population Health And Health Disparities Program Project Sponsored By The National Cancer Institute

Faculty, Staff and Students Publications

BACKGROUND: The smoking behavior of American Indians (AI) differs from that of non-Hispanic whites (NHW). Typically light smokers, cessation interventions in AIs are generally less effective. To develop more effective cessation programs for AIs, clinicians, researchers, and public health workers need a better understanding of the genetic factors involved in their smoking behavior. Our aim was to assess whether SNPs associated with smoking behavior in NHWs are also associated with smoking in AIs.

METHODS: We collected questionnaire data on smoking behaviors and analyzed blood and saliva samples from two Tribal populations with dramatically different cultures and smoking prevalence, one in …


Depot Medroxyprogesterone Acetate Use And Blood Lead Levels In A Cohort Of Young Women, Kristen Upson, Quaker E. Harmon, Renee Heffron, Janet E. Hall, Lauren A. Wise, Ganesa Wegienka, Erik J. Tokar, Donna D. Baird Nov 2020

Depot Medroxyprogesterone Acetate Use And Blood Lead Levels In A Cohort Of Young Women, Kristen Upson, Quaker E. Harmon, Renee Heffron, Janet E. Hall, Lauren A. Wise, Ganesa Wegienka, Erik J. Tokar, Donna D. Baird

Public Health Sciences Articles

BACKGROUND: Injectable contraceptive use is common, with 74 million users worldwide. Use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) is associated with bone mineral density loss. We hypothesize that increased bone resorption with DMPA use allows for mobilization of the toxic metal lead stored in bone to blood, presenting users with increased systemic exposure to lead.

OBJECTIVE: The objective of our study was to investigate the association between current DMPA use and blood lead concentrations.

METHODS: We conducted a cross-sectional analysis using enrollment data from the Study of Environment, Lifestyle & Fibroids (SELF), a cohort of 1,693 African-American women …


Transfusion Of Blood Components Containing Abo-Incompatible Plasma Does Not Lead To Higher Mortality In Civilian Trauma Patients, Jansen N. Seheult, Nancy M. Dunbar, John R. Hess, Erin E. Tuott, Mohammad Bahmanyar, Jessica Campbell, Magali Fontaine, Jenna Khan, Ara Ko, Jian Mi, Michael F. Murphy, Tara Nykoluk, Jessica Poisson, Jay S. Raval, Andrew Shih, Jason L. Sperry, Julie Staves, Michelle Wong, Matthew T S Yan, Alyssa Ziman, Mark H. Yazer Nov 2020

Transfusion Of Blood Components Containing Abo-Incompatible Plasma Does Not Lead To Higher Mortality In Civilian Trauma Patients, Jansen N. Seheult, Nancy M. Dunbar, John R. Hess, Erin E. Tuott, Mohammad Bahmanyar, Jessica Campbell, Magali Fontaine, Jenna Khan, Ara Ko, Jian Mi, Michael F. Murphy, Tara Nykoluk, Jessica Poisson, Jay S. Raval, Andrew Shih, Jason L. Sperry, Julie Staves, Michelle Wong, Matthew T S Yan, Alyssa Ziman, Mark H. Yazer

Pathology Research and Scholarship

BACKGROUND: This study investigated the effect on mortality of transfusing ABO-incompatible plasma from all sources during trauma resuscitation.

METHODS: Demographic, transfusion, and survival data were retrospectively extracted on civilian trauma patients. Patients were divided by receipt of any quantity of ABO-incompatible plasma from any blood product (incompatible group) or receipt of solely ABO-compatible plasma (compatible group). The primary outcome was 30-day mortality, while other outcomes included 6- and 24-hour mortality. Mixed-effects logistic regression was used to model the effect of various predictor variables, including receipt of incompatible plasma, on mortality outcomes.

RESULTS: Nine hospitals contributed data on a total of …


Prospective, Randomized, Double-Blind, Placebo-Controlled Evaluation Of The Pharmacokinetics, Safety And Efficacy Of Recombinant Antithrombin Versus Placebo In Preterm Preeclampsia, Michael J Paidas, George A Macones, Et Al Nov 2020

Prospective, Randomized, Double-Blind, Placebo-Controlled Evaluation Of The Pharmacokinetics, Safety And Efficacy Of Recombinant Antithrombin Versus Placebo In Preterm Preeclampsia, Michael J Paidas, George A Macones, Et Al

Open Access Publications

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system.

OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes.

STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned …


The Arabic Version Of The Personality Inventory For The Dsm-5 (Pid-5) In A Clinical Sample Of United Arab Emirates (Uae) Nationals, Olga Coelho, Rute Pires, Ana Sousa Ferreira, Bruno Gonçalves, Samia A. Alkhoori, Mohamed A. Sayed, Amany Elrasheed, Sara Belhoul, Maryam Aljassmi, Joana Stocker Nov 2020

The Arabic Version Of The Personality Inventory For The Dsm-5 (Pid-5) In A Clinical Sample Of United Arab Emirates (Uae) Nationals, Olga Coelho, Rute Pires, Ana Sousa Ferreira, Bruno Gonçalves, Samia A. Alkhoori, Mohamed A. Sayed, Amany Elrasheed, Sara Belhoul, Maryam Aljassmi, Joana Stocker

All Works

Objectives: We aimed to test the potential of the Arabic version of the PID-5 to distinguish between clinical and non-clinical participants, as well as to examine its convergent validity and factor structure in an Emirati clinical sample. Methods: The Arabic version of the PID-5 was administered to a clinical sample comprised of 156 participants (Mage = 31.38, SD = 8.99, 37.8% male, 62.2% female) and a community sample also comprised of 156 participants (Mage = 31.43, SD = 9.52, 37.2% male, 62.8% female). We addressed the descriptive measures, internal consistency, mean rank scores differences, convergent validity with SCL-90-R, and PID-5's …


Brain Function Distinguishes Female Carriers And Non-Carriers Of Familial Risk For Autism, Adam T Eggebrecht, Ally Dworetsky, Zoë Hawks, Rebecca Coalson, Babatunde Adeyemo, Savannah Davis, Daniel Gray, Alana Mcmichael, Steven E Petersen, John N Constantino, John R Pruett Oct 2020

Brain Function Distinguishes Female Carriers And Non-Carriers Of Familial Risk For Autism, Adam T Eggebrecht, Ally Dworetsky, Zoë Hawks, Rebecca Coalson, Babatunde Adeyemo, Savannah Davis, Daniel Gray, Alana Mcmichael, Steven E Petersen, John N Constantino, John R Pruett

2020-Current year OA Pubs

BACKGROUND: Autism spectrum disorder (ASD) is characterized by high population-level heritability and a three-to-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed ("carrier") females.

METHODS: Using functional magnetic resonance imaging, we examined brain responses to passive …


Health And Disease Markers Correlate With Gut Microbiome Composition Across Thousands Of People., Ohad Manor, Chengzhen L Dai, Sergey A Kornilov, Brett Smith, Nathan D Price, Jennifer C Lovejoy, Sean M Gibbons, Andrew T Magis Oct 2020

Health And Disease Markers Correlate With Gut Microbiome Composition Across Thousands Of People., Ohad Manor, Chengzhen L Dai, Sergey A Kornilov, Brett Smith, Nathan D Price, Jennifer C Lovejoy, Sean M Gibbons, Andrew T Magis

Articles, Abstracts, and Reports

Variation in the human gut microbiome can reflect host lifestyle and behaviors and influence disease biomarker levels in the blood. Understanding the relationships between gut microbes and host phenotypes are critical for understanding wellness and disease. Here, we examine associations between the gut microbiota and ~150 host phenotypic features across ~3,400 individuals. We identify major axes of taxonomic variance in the gut and a putative diversity maximum along the Firmicutes-to-Bacteroidetes axis. Our analyses reveal both known and unknown associations between microbiome composition and host clinical markers and lifestyle factors, including host-microbe associations that are composition-specific. These results suggest potential opportunities …


Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Titers In Convalescent Plasma And Recipients In New Mexico: An Open Treatment Study In Patients With Coronavirus Disease 2019, Steven B. Bradfute, Ivy Hurwitz, Alexandra V. Yingling, Chunyan Ye, Qiuying Cheng, Timothy P Noonan, Jay S. Raval, Nestor R. Sosa, Gregory J. Mertz, Douglas J. Perkins, Michelle S. Harkins Oct 2020

Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Titers In Convalescent Plasma And Recipients In New Mexico: An Open Treatment Study In Patients With Coronavirus Disease 2019, Steven B. Bradfute, Ivy Hurwitz, Alexandra V. Yingling, Chunyan Ye, Qiuying Cheng, Timothy P Noonan, Jay S. Raval, Nestor R. Sosa, Gregory J. Mertz, Douglas J. Perkins, Michelle S. Harkins

Pathology Research and Scholarship

BACKGROUND: Convalescent plasma (CP) is a potentially important therapy for coronavirus disease 2019 (COVID-19). However, knowledge regarding neutralizing antibody (NAb) titers in donor plasma and their impact in patients with acute COVID-19 remains largely undetermined. We measured NAb titers in CP and in patients with acute COVID-19 before and after transfusion through the traditional Food and Drug Administration investigational new drug pathway.

METHODS: We performed a single-arm interventional trial measuring NAb and total antibody titers before and after CP transfusion over a 14-day period in hospitalized patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection.

RESULTS: NAb titers in …


Adaptive Thermogenesis Enhances The Life-Threatening Response To Heat In Mice With An Ryr1 Mutation, Hui J Wang, Chang Seok Lee, Rachel Sue Zhen Yee, Linda Groom, Inbar Friedman, Lyle Babcock, Dimitra K Georgiou, Jin Hong, Amy D Hanna, Joseph Recio, Jong Min Choi, Ting Chang, Nadia H Agha, Jonathan Romero, Poonam Sarkar, Nicol Voermans, M Waleed Gaber, Sung Yun Jung, Matthew L Baker, Robia G Pautler, Robert T Dirksen, Sheila Riazi, Susan L Hamilton Oct 2020

Adaptive Thermogenesis Enhances The Life-Threatening Response To Heat In Mice With An Ryr1 Mutation, Hui J Wang, Chang Seok Lee, Rachel Sue Zhen Yee, Linda Groom, Inbar Friedman, Lyle Babcock, Dimitra K Georgiou, Jin Hong, Amy D Hanna, Joseph Recio, Jong Min Choi, Ting Chang, Nadia H Agha, Jonathan Romero, Poonam Sarkar, Nicol Voermans, M Waleed Gaber, Sung Yun Jung, Matthew L Baker, Robia G Pautler, Robert T Dirksen, Sheila Riazi, Susan L Hamilton

Faculty, Staff and Students Publications

Mutations in the skeletal muscle Ca2+ release channel, the type 1 ryanodine receptor (RYR1), cause malignant hyperthermia susceptibility (MHS) and a life-threatening sensitivity to heat, which is most severe in children. Mice with an MHS-associated mutation in Ryr1 (Y524S, YS) display lethal muscle contractures in response to heat. Here we show that the heat response in the YS mice is exacerbated by brown fat adaptive thermogenesis. In addition, the YS mice have more brown adipose tissue thermogenic capacity than their littermate controls. Blood lactate levels are elevated in both heat-sensitive MHS patients with RYR1 mutations and YS mice due to …


Risk Prediction Rule For Advanced Neoplasia On Screening Colonoscopy For Average-Risk Individuals, Ala I Sharara, Ali El Mokahal, Ali H Harb, Natalia Khalaf, Fayez S Sarkis, Mustapha M El-Halabi, Nabil M Mansour, Ahmad Malli, Robert Habib Oct 2020

Risk Prediction Rule For Advanced Neoplasia On Screening Colonoscopy For Average-Risk Individuals, Ala I Sharara, Ali El Mokahal, Ali H Harb, Natalia Khalaf, Fayez S Sarkis, Mustapha M El-Halabi, Nabil M Mansour, Ahmad Malli, Robert Habib

Faculty, Staff and Students Publications

BACKGROUND: In resource-limited countries, risk stratification can be used to optimize colorectal cancer screening. Few prospective risk prediction models exist for advanced neoplasia (AN) in true average-risk individuals.

AIM: To create and internally validate a risk prediction model for detection of AN in average-risk individuals.

METHODS: Prospective study of asymptomatic individuals undergoing first screening colonoscopy. Detailed characteristics including diet, exercise and medications were collected. Multivariate logistic regression was used to elucidate risk factors for AN (adenoma ≥1 cm, villous histology, high-grade dysplasia or carcinoma). The model was validated through bootstrapping, and discrimination and calibration of the model were assessed.

RESULTS: …


At Three Years, Patients With Acute Lymphoblastic Leukaemia Are Still At Risk For Relapse. Results Of The International Mrc Ukallxii/Ecog E2993 Trial, Chezi Ganzel, Xin V. Wang, Jacob M. Rowe, Susan M. Richards, Georgina Buck, David I. Marks, Mark R. Litzow, Elisabeth M. Paietta, Letizia Foroni, Selina M. Luger, Cheryl L. Willman, Charles G. Mullighan, Kathryn G. Roberts, Peter H. Wiernik, Dan Douer, Hillard M. Lazarus, Martin S. Tallman, Anthony H. Goldstone Oct 2020

At Three Years, Patients With Acute Lymphoblastic Leukaemia Are Still At Risk For Relapse. Results Of The International Mrc Ukallxii/Ecog E2993 Trial, Chezi Ganzel, Xin V. Wang, Jacob M. Rowe, Susan M. Richards, Georgina Buck, David I. Marks, Mark R. Litzow, Elisabeth M. Paietta, Letizia Foroni, Selina M. Luger, Cheryl L. Willman, Charles G. Mullighan, Kathryn G. Roberts, Peter H. Wiernik, Dan Douer, Hillard M. Lazarus, Martin S. Tallman, Anthony H. Goldstone

Pathology Research and Scholarship

Late relapse [>3 years from complete remission (CR)] in acute lymphoblastic leukaemia (ALL), is unusual. Data from the MRC UKALLXII/ECOG E2993 trial are presented to evaluate the incidence and characteristics of late relapse in adult ALL. Of 1,909 patients, 1,752 (92%) achieved CR and among these 757 (43·2%) relapsed; 691 (91·3%) within three years and 66 (8·7%) beyond. Among these 66 patients, median time to relapse was 47 (37-144) months. Relapse beyond three years occurred in 3·8% of all who achieved CR. The cumulative risk of relapse was 40%, 43% and 45% at three, five and ten years respectively. …


Phase 1 Study Of The Mdm2 Antagonist Ro6839921 In Patients With Acute Myeloid Leukemia, Geoffrey L Uy, Sarit Assouline, Anne-Marie Young, Steven Blotner, Brian Higgins, Lin-Chi Chen, Karen Yee Oct 2020

Phase 1 Study Of The Mdm2 Antagonist Ro6839921 In Patients With Acute Myeloid Leukemia, Geoffrey L Uy, Sarit Assouline, Anne-Marie Young, Steven Blotner, Brian Higgins, Lin-Chi Chen, Karen Yee

2020-Current year OA Pubs

In acute myeloid leukemia (AML), TP53 mutations and dysregulation of wild-type p53 is common and supports an MDM2 antagonist as a therapy. RO6839921 is an inactive pegylated prodrug of the oral MDM2 antagonist idasanutlin (active principle [AP]) that allows for IV administration. This phase 1 monotherapy study evaluated the safety, pharmacokinetics, and pharmacodynamics of RO6839921 in patients with AML. Primary objectives identified dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary objectives assessed pharmacokinetic, pharmacodynamic, and antileukemic activity. A total of 26 patients received 120-300 mg AP of idasanutlin. The MTD was 200 mg, with DLTs at 250 (2/8 patients) …


Antibodies To Variable Domain 4 Linear Epitopes Of The Chlamydia Trachomatis Major Outer Membrane Protein Are Not Associated With Chlamydia Resolution Or Reinfection In Women, Amanda L. Collar, Alexandria C. Linville, Susan B. Core, Cosette M. Wheeler, William M. Geisler, David S. Peabody, Bryce Chackerian, Kathryn M. Frietze Sep 2020

Antibodies To Variable Domain 4 Linear Epitopes Of The Chlamydia Trachomatis Major Outer Membrane Protein Are Not Associated With Chlamydia Resolution Or Reinfection In Women, Amanda L. Collar, Alexandria C. Linville, Susan B. Core, Cosette M. Wheeler, William M. Geisler, David S. Peabody, Bryce Chackerian, Kathryn M. Frietze

Pathology Research and Scholarship

Chlamydia trachomatis is an obligate intracellular bacterium. C. trachomatis infection is the most prevalent bacterial sexually transmitted infection and can lead to pelvic inflammatory disease and infertility in women. There is no licensed vaccine for C. trachomatis prevention, in part due to gaps in our knowledge of C. trachomatis-specific immune responses elicited during human infections. Previous investigations of the antibody response to C. trachomatis have identified immunodominant antigens and antibodies that can neutralize infection in cell culture. However, epitope-specific responses to C. trachomatis are not well characterized, and the impact of these antibodies on infection outcome is unknown. We …


A Novel Bioaugmentation Technique Effectively Increases The Skin-Associated Microbial Diversity Of Captive Eastern Hellbenders, Erin K. Kenison, Obed Hernandez-Gomez, Rod N. Williams Sep 2020

A Novel Bioaugmentation Technique Effectively Increases The Skin-Associated Microbial Diversity Of Captive Eastern Hellbenders, Erin K. Kenison, Obed Hernandez-Gomez, Rod N. Williams

Natural Sciences and Mathematics | Faculty Scholarship

Captive environments are maintained in hygienic ways that lack free-flowing microbes found in animals’ natural environments. As a result, captive animals often have depauperate host-associated microbial communities compared to conspecifics in the wild and may have increased disease susceptibility and reduced immune function. Eastern hellbenders (Cryptobranchus alleganiensis alleganiensis) have suffered precipitous population declines over the past few decades. To bolster populations, eastern hellbenders are reared in captivity before being translocated to the wild. However, the absence of natural microbial reservoirs within the captive environment diminishes the diversity of skin-associated bacteria on hellbender skin and may negatively influence their ability to …


Applying The Who Icf Framework To The Outcome Measures Used In The Evaluation Of Long-Term Clinical Outcomes In Coronavirus Outbreaks, Kajal Patel, Sofia Straudi, Ng Yee Sien, Nora Fayed, John L. Melvin, Manoj Sivan Sep 2020

Applying The Who Icf Framework To The Outcome Measures Used In The Evaluation Of Long-Term Clinical Outcomes In Coronavirus Outbreaks, Kajal Patel, Sofia Straudi, Ng Yee Sien, Nora Fayed, John L. Melvin, Manoj Sivan

Department of Rehabilitation Medicine Faculty Papers

(1) Objective: The World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF) classification is a unified framework for the description of health and health-related states. This study aimed to use the ICF framework to classify outcome measures used in follow-up studies of coronavirus outbreaks and make recommendations for future studies. (2) Methods: EMBASE, MEDLINE, CINAHL and PsycINFO were systematically searched for original studies assessing clinical outcomes in adult survivors of severe acute respiratory distress syndrome (SARS), middle east respiratory syndrome (MERS) and coronavirus disease-19 (COVID-19) after hospital discharge. Individual items of the identified outcome measures were linked …


Severe Immunosuppression And Not A Cytokine Storm Characterizes Covid-19 Infections, Kenneth E Remy, Monty Mazer, David A Striker, Ali H Ellebedy, Andrew H Walton, Jacqueline Unsinger, Teresa M Blood, Philip A Mudd, Daehan J Yi, Daniel A Mannion, Dale F Osborne, R Scott Martin, Nitin J Anand, James P Bosanquet, Jane Blood, Anne M Drewry, Charles C Caldwell, Isaiah R Turnbull, Scott C Brakenridge, Lyle L Moldwawer, Richard S Hotchkiss Sep 2020

Severe Immunosuppression And Not A Cytokine Storm Characterizes Covid-19 Infections, Kenneth E Remy, Monty Mazer, David A Striker, Ali H Ellebedy, Andrew H Walton, Jacqueline Unsinger, Teresa M Blood, Philip A Mudd, Daehan J Yi, Daniel A Mannion, Dale F Osborne, R Scott Martin, Nitin J Anand, James P Bosanquet, Jane Blood, Anne M Drewry, Charles C Caldwell, Isaiah R Turnbull, Scott C Brakenridge, Lyle L Moldwawer, Richard S Hotchkiss

Open Access Publications

COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results in unrestrained viral dissemination and organ injury. A key explanation for the inability to address this controversy has been the lack of diagnostic tools to evaluate immune function in COVID-19 infections. ELISpot, a highly sensitive, functional immunoassay, was employed in 27 patients with COVID-19, 51 patients with sepsis, 18 critically ill nonseptic (CINS) patients, and 27 healthy control volunteers to evaluate adaptive and innate immune status by quantitating T cell IFN-ɣ …


Heterogeneity Of Mild To Moderate Persistent Asthma In Children: Confirmation By Latent Class Analysis And Association With 1-Year Outcomes, Anne M. Fitzpatrick, Leonard B. Bacharier, Daniel J. Jackson, Stanley J. Szefler, Avraham Beigelman, Michael Cabana, Ronina Covar, Theresa Guilbert, Fernando Holguin, Robert F. Lemanske, Fernando D. Martinez, Wayne Morgan, Wanda Phipatanakul, Jacqueline A. Pongracic, Hengameh H. Raissy, Robert S. Zeiger, David T. Mauger Sep 2020

Heterogeneity Of Mild To Moderate Persistent Asthma In Children: Confirmation By Latent Class Analysis And Association With 1-Year Outcomes, Anne M. Fitzpatrick, Leonard B. Bacharier, Daniel J. Jackson, Stanley J. Szefler, Avraham Beigelman, Michael Cabana, Ronina Covar, Theresa Guilbert, Fernando Holguin, Robert F. Lemanske, Fernando D. Martinez, Wayne Morgan, Wanda Phipatanakul, Jacqueline A. Pongracic, Hengameh H. Raissy, Robert S. Zeiger, David T. Mauger

Pediatrics Research and Scholarship

BACKGROUND: Compared with adults, phenotypic characterization of children with asthma is still limited and it remains difficult to predict which children with asthma are at highest risk for poor outcomes.

OBJECTIVE: To identify latent classes in a large population of treatment-adherent children with mild to moderate asthma enrolled in clinical trials and determine whether latent class assignment predicts future lung function abnormalities and exacerbation rate.

METHODS: Latent class analysis was performed on 2593 children with mild to moderate asthma aged 5 18 years, with 19 variables encompassing demographic characteristics, medical history, symptoms, lung function, allergic sensitization, and type 2 inflammation. …


Self-Regulation And Emotional Reactivity In Infants With Prenatal Exposure To Opioids And Alcohol, Kathryn G Beauchamp, Jean Lowe, Ronald M Schrader, Shikhar Shrestha, Crystal Aragón, Natalia Moss, Julia M Stephen, Ludmila N Bakhireva Sep 2020

Self-Regulation And Emotional Reactivity In Infants With Prenatal Exposure To Opioids And Alcohol, Kathryn G Beauchamp, Jean Lowe, Ronald M Schrader, Shikhar Shrestha, Crystal Aragón, Natalia Moss, Julia M Stephen, Ludmila N Bakhireva

Pediatrics Research and Scholarship

BACKGROUND: Infants with prenatal substance exposure are at increased risk for developmental problems, with self-regulatory challenges being some of the most pronounced. The current study aimed to investigate the extent to which prenatal substance exposure (alcohol, opioids) impacts infant self-regulation during a relational stressor and the association between self-regulation and infant affect.

METHODS: Participants were 100 mother-child dyads recruited prenatally (Mean = 23.8 gestational weeks) and completed the Still Face Paradigm (SFP) when infants were 5 to 8 months of age (Mean = 6.9 months) as part of an ENRICH prospective birth cohort study. Based on prospective repeated assessment of …


Postmortem Computed Tomography In Firearm Homicides: A Retrospective Case Series, Marloes E M Vester, Kurt B Nolte, Gary M. Hatch, Chandra Y. Gerrard, Reinoud D. Stoel, Rick R. Van Rijn Sep 2020

Postmortem Computed Tomography In Firearm Homicides: A Retrospective Case Series, Marloes E M Vester, Kurt B Nolte, Gary M. Hatch, Chandra Y. Gerrard, Reinoud D. Stoel, Rick R. Van Rijn

Pathology Research and Scholarship

Postmortem computed tomography (PMCT) is integrated into the evaluation of decedents in several American medical examiner offices and medicolegal death investigative centers in many other countries. We retrospectively investigated the value of PMCT in a series of firearm homicide cases from a statewide centralized medical examiner's office that occurred during 2016. Autopsies were performed or supervised by board-certified forensic pathologists who reviewed the PMCT scans prior to autopsy. PMCT scans were re-evaluated by a forensic radiologist blinded to the autopsy findings and scored by body region (head-neck, thoracoabdominal, and extremities). Injury discrepancies were scored using a modified Goldman classification and …


Deletion Rescue Resulting In Segmental Homozygosity: A Mechanism Underlying Discordant Nipt Results, Samantha Caldwell, Katelynn Sagaser, Zoe Nelson, Jennifer Frey, Jenna Wardrop, Theresa Boomer, Ron Mccullough, Stuart Schwartz Aug 2020

Deletion Rescue Resulting In Segmental Homozygosity: A Mechanism Underlying Discordant Nipt Results, Samantha Caldwell, Katelynn Sagaser, Zoe Nelson, Jennifer Frey, Jenna Wardrop, Theresa Boomer, Ron Mccullough, Stuart Schwartz

Research Administration Articles

With the increasing capabilities of non-invasive prenatal testing (NIPT), detection of sub-chromosomal deletions and duplications are possible. This case series of deletion rescues resulting in segmental homozygosity helps provide a biological explanation for NIPT discrepancies and adds to the dearth of existing literature surrounding segmental UPD cases and their underlying mechanisms. In the three cases presented here, NIPT reported a sub-chromosomal deletion (in isolation or as part of a complex finding). Diagnostic testing, however, revealed segmental homozygosity or UPD for the region reported deleted on NIPT. Postnatal placental testing was pursued in two cases and confirmed the NIPT findings. This …