Medicine and Health Sciences Commons^™

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

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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 …

Does Covid-19 Contribute To Development Of Neurological Disease?, Arehally M. Mahalakshmi, Bipul Ray, Sunanda Tuladhar, Abid Bhat, Shasthara Paneyala, Duraisamy Patteswari, Meena K. Sakharkar, Hamdan Hamdan, David M. Ojcius, Srinivasa R. Bolla, Musthafa M. Essa, Saravana B. Chidambaram, M. Walid Qoronfleh

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Background: Although coronavirus disease 2019 (COVID-19) has been associated primarily with pneumonia, recent data show that the causative agent of COVID-19, the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can infect a large number of vital organs beyond the lungs, such as the heart, kidneys, and the brain. Thus, there is evidence showing possible retrograde transmission of the virus from the olfactory epithelium to regions of the brain stem. Methods: This is a literature review article. The research design method is an evidence-based rapid review. The present discourse aim is first to scrutinize and assess the available literature on …

Vopo Leverages Cellular Heterogeneity For Predictive Modeling Of Single-Cell Data, Natalie Stanley, Ina A. Stelzer, Amy S. Tsai, Ramin Fallahzadeh, Edward A. Ganio, Martin Becker, Thanaphong Phongpreecha, Huda Nassar, Sajjad Ghaemi, Ivana Maric, Anthony Culos, Alan L. Chang, Maria Xenochristou, Xiaoyuan Han, Camilo Espinosa, Kristen Rumer, Laura Peterson, Franck Verdonk, Dyani Gaudilliere, Eileen Tsai, Dorien Feyaerts, Jakob Einhaus, Kazuo Ando, Ronald J. Wong, Gerlinde Obermoser, Gary M. Shaw, David K. Stevenson, Martin S. Angst, Brice Gaudilliere

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High-throughput single-cell analysis technologies produce an abundance of data that is critical for profiling the heterogeneity of cellular systems. We introduce VoPo (https://github.com/stanleyn/VoPo), a machine learning algorithm for predictive modeling and comprehensive visualization of the heterogeneity captured in large single-cell datasets. In three mass cytometry datasets, with the largest measuring hundreds of millions of cells over hundreds of samples, VoPo defines phenotypically and functionally homogeneous cell populations. VoPo further outperforms state-of-the-art machine learning algorithms in classification tasks, and identified immune-correlates of clinically-relevant parameters.

Noninvasive Temporal Detection Of Early Retinal Vascular Changes During Diabetes, Mohammad A. Saghiri, Andrew Suscha, Shoujian Wang, Ali M. Saghiri, Christine M. Sorenson, Nader Sheibani

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Diabetes associated complications, including diabetic retinopathy and loss of vision, are major health concerns. Detecting early retinal vascular changes during diabetes is not well documented, and only few studies have addressed this domain. The purpose of this study was to noninvasively evaluate temporal changes in retinal vasculature at very early stages of diabetes using fundus images from preclinical models of diabetes.Non-diabetic and Akita/+ male mice with different duration of diabetes were subjected to fundus imaging using a Micron III imaging system. The images were obtained from 4 weeks- (onset of diabetes), 8 weeks-, 16 weeks-, and 24 weeks-old male Akita/+ …

Integration Of Mechanistic Immunological Knowledge Into A Machine Learning Pipeline Improves Predictions, Anthony Culos, Amy S. Tsai, Natalie Stanley, Martin Becker, Mohammad S. Ghaemi, David R. Mcilwain, Ramin Fallahzadeh, Athena Tanada, Huda Nassar, Camilo Espinosa, Maria Xenochristou, Edward Ganio, Laura Peterson, Xiaoyuan Han, Ina A. Stelzer, Kazuo Ando, Dyani Gaudilliere, Thanaphong Phongpreecha, Ivana Marić, Alan L. Chang, Gary M. Shaw, David K. Stevenson, Sean Bendall, Kara L. Davis, Wendy Fantl, Garry P. Nolan, Trevor Hastie, Robert Tibshirani, Martin S. Angst

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The dense network of interconnected cellular signalling responses that are quantifiable in peripheral immune cells provides a wealth of actionable immunological insights. Although high-throughput single-cell profiling techniques, including polychromatic flow and mass cytometry, have matured to a point that enables detailed immune profiling of patients in numerous clinical settings, the limited cohort size and high dimensionality of data increase the possibility of false-positive discoveries and model overfitting. We introduce a generalizable machine learning platform, the immunological Elastic-Net (iEN), which incorporates immunological knowledge directly into the predictive models. Importantly, the algorithm maintains the exploratory nature of the high-dimensional dataset, allowing for …

Multiomic Immune Clockworks Of Pregnancy, Laura S. Peterson, Ina A. Stelzer, Amy S. Tsai, Mohammad S. Ghaemi, Xiaoyuan Han, Kazuo Ando, Virginia D. Winn, Nadine R. Martinez, Kevin Contrepois, Mira N. Moufarrej, Stephen Quake, David A. Relman, Michael P. Snyder, Gary M. Shaw, David K. Stevenson, Ronald J. Wong, Petra Arck, Martin S. Angst, Nima Aghaeepour, Brice Gaudilliere

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Preterm birth is the leading cause of mortality in children under the age of five worldwide. Despite major efforts, we still lack the ability to accurately predict and effectively prevent preterm birth. While multiple factors contribute to preterm labor, dysregulations of immunological adaptations required for the maintenance of a healthy pregnancy is at its pathophysiological core. Consequently, a precise understanding of these chronologically paced immune adaptations and of the biological pacemakers that synchronize the pregnancy “immune clock” is a critical first step towards identifying deviations that are hallmarks of peterm birth. Here, we will review key elements of the fetal, …

Is There An Association Between Oral Health And Severity Of Covid-19 Complications?, Nathalie Botros, Parvati Iyer, David M. Ojcius

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Most patients with severe complications from COVID-19 have underlying conditions such as obesity, diabetes, and hypertension. In parallel, there is growing evidence for a link between periodontitis and non-oral systemic diseases. The oral cavity is also a reservoir for respiratory pathogens, and patients with periodontal disease are more likely to develop hospital-acquired pneumonia than healthy individuals. We therefore hypothesize that improving oral health could decrease the severity of COVID-19 symptoms and reduce the associated morbidity.

Plant And Fungal Products That Extend Lifespan In Caenorhabditis Elegans, Jan Martel, Cheng Yeu Wu, Hsin Hsin Peng, Yun Fei Ko, Hung Chi Yang, John D. Young, David M. Ojcius

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The nematode Caenorhabditis elegans is a useful model to study aging due to its short lifespan, ease of manipulation, and available genetic tools. Several molecules and extracts derived from plants and fungi extend the lifespan of C. elegans by modulating aging-related pathways that are conserved in more complex organisms. Modulation of aging pathways leads to activation of autophagy, mitochondrial biogenesis and expression of antioxidant and detoxifying enzymes in a manner similar to caloric restriction. Low and moderate concentrations of plant and fungal molecules usually extend lifespan, while high concentrations are detrimental, consistent with a lifespan-modulating mechanism involving hormesis. We review …

Cbl Negatively Regulates Nlrp3 Inflammasome Activation Through Glut1-Dependent Glycolysis Inhibition, Hsin Chung Lin, Yu Jen Chen, Yau Huei Wei, Yu Ting Chuang, Su Heng Hsieh, Jing Yu Hsieh, Yi Lin Hsieh, David M. Ojcius, Kuo Yang Huang, I. Che Chung, Sheng Ning Yuan, Yu Sun Chang, Lih Chyang Chen

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Activation of the nod-like receptor 3 (NLRP3) inflammasomes is crucial for immune defense, but improper and excessive activation causes inflammatory diseases. We previously reported that Cbl plays a pivotal role in suppressing NLRP3 inflammasome activation by inhibiting Pyk2-mediated apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization. Here, we showed that Cbl dampened NLRP3 inflammasome activation by inhibiting glycolysis, as demonstrated with Cbl knockout cells and treatment with the Cbl inhibitor hydrocotarnine. We revealed that the inhibition of Cbl promoted caspase-1 cleavage and interleukin (IL)-1β secretion through a glycolysis-dependent mechanism. Inhibiting Cbl increased cellular glucose uptake, glycolytic capacity, and mitochondrial oxidative …

Impact Of Covid-19 On Dental Education In The United States, Parvati Iyer, Kalid Aziz, David M. Ojcius

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© 2020 American Dental Education Association Dental institutions in the United States are reeling from the consequences of the novel SARS-CoV2 coronavirus, the causative agent of CODIV-19. As oral health care providers, we have been trained on prevention of aerosol transmissible diseases, but we are still grappling with many unknown factors regarding COVID-19. While the Centers for Disease Control and Prevention (CDC), American Dental Association (ADA), and local state agencies are releasing updates on guidelines for dentists and patients, no official information exists for dental institutions on how to effectively follow the recommended guidelines including “shelter in place” with social …

The Three-Dimensional Stable Mandibular Landmarks In Patients Between The Ages Of 12.5 And 17.1 Years, Gui Chen, Mona Al Awadi, David W. Chambers, Manuel O. Lagravère-Vich, Tianmin Xu, Heesoo Oh

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Background: With the aid of implants, Björk identified two-dimensional mandibular stable structures in cephalograms during facial growth. However, we do not know what the three-dimensional stable structures are with certainty. The purpose of this study was to identify the most stable mandibular landmarks in growing patients using three-dimensional images. Methods: The sample was comprised of two cone-beam computed tomography (CBCT) scans taken about 4.6 years apart in 20 growing patients between the ages of 12.5 (T1) and 17.1 years (T2). After head orientation, landmarks were located on the chin (Pog), internal symphysis (Points C, D and E), and mandibular canals, …

S-Seco-Porphyrazine As A New Member Of The Seco-Porphyrazine Family – Synthesis, Characterization And Photocytotoxicity Against Cancer Cells, Dariusz T. Mlynarczyk, Jaroslaw Piskorz, Lukasz Popenda, Magdalena Stolarska, Wojciech Szczolko, Krystyna Konopka, Stefan Jurga, Lukasz Sobotta, Jadwiga Mielcarek, Nejat Düzgüneş, Tomasz Goslinski

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An important subgroup within the porphyrazine (Pz) family constitutes seco-porphyrazines, in the chemical structure of which one pyrrole unit is opened in the oxidative process. So far, there are only limited data on N-seco- and C-seco-Pzs. Here, the synthesis of a novel member of the Pzs seco-family, represented by an S-seco-tribenzoporphyrazine analogue, 22,23-bis(4-(3,5-dibutoxycarbonylphenoxy)butylsulfanyl)tribenzo[b,g,l]-22,23-dioxo-22,23-seco-porphyrazinato magnesium(II), is reported, with moderate 34% yield. The new derivative was characterized using NMR spectroscopy, UV–Vis spectroscopy, and mass spectrometry. In the photochemical study performed following the indirect chemical method with 1,3-diphenylisobenzofuran, S-seco-Pz revealed a high singlet oxygen quantum yield of 0.27 in DMF. Potential photocytotoxicity of …

The Role Of Glial Cell Derived Neurotrophic Factor In Head And Neck Cancer, Hongbin Cao, Qian He, Rie Von Eyben, Joshua Bloomstein, Dhanya K. Nambiar, Vignesh Viswanathan, Sonya Aggarwal, Shirley Kwok, Rachel Liang, Amanda J. Koong, James S. Lewis Jr., Christina Kong, Nan Xiao, Quynh-Thu Le

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Glial cell-derived neurotrophic factor (GDNF) is reported to promote the survival of neurons and salivary gland regeneration after radiation damage. This study investigated the effect of GDNF on cell migration, growth, and response to radiation in preclinical models of head and neck squamous cell carcinoma (HNSCC) and correlated GDNF expression to treatment outcomes in HNSCC patients. Our ultimate goal is to determine whether systemic administration of GDNF at high dose is safe for the management of hyposalivation or xerostomia in HNSCC patients. Three HPV-positive and three HPV-negative cell lines were examined for cell migration, growth, and clonogenic survival in vitro …

Possible Role Of Tryptophan And Melatonin In Covid-19, Musthafa Mohamed Essa, Hamdan Hamdan, Saravana Babu Chidambaram, Buthainah Al-Balushi, Gilles J. Guillemin, David M. Ojcius, M. Walid Qoronfleh

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No abstract provided.

Mitochondrial Oxidative Phosphorylation Complex Regulates Nlrp3 Inflammasome Activation And Predicts Patient Survival In Nasopharyngeal Carcinoma, I. Che Chung, Lih Chyang Chen, Ngan Ming Tsang, Wen Yu Chuang, Tzu Chieh Liao, Sheng Ning Yuan, Chun Nan Ouyang, David M. Ojcius, Chih Ching Wu, Yu Sun Chang

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© 2020 Chung et al. We previously reported that tumor inflammasomes play a key role in tumor control and act as favorable prognostic markers in nasopharyngeal carcinoma (NPC). Activated inflammasomes frequently form distinguishable specks and govern the cellular secretion of IL-1β. However, we know little about the biological and biochemical differences between cells with and without apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) speck formation. In this study, we used proteomic iTRAQ analysis to analyze the proteomes of NPC cells that differ in their ASC speck formation upon cisplatin treatment. We identified proteins that were differentially over-expressed in cells …

Immune Response Against Chlamydia Trachomatis Via Toll-Like Receptors Is Negatively Regulated By Sigirr, Mufadhal Al-Kuhlani, Graham Lambert, Sukumar Pal, Luis De La Maza, David M. Ojcius

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Copyright: © 2020 Al-Kuhlani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Chlamydia trachomatis is the most common bacterial sexually-transmitted infection and the major cause of preventable blindness worldwide. The asymptomatic nature of many infections along with uncontrolled inflammation leads to irreversible damage in the upper genital tract and the tarsal conjunctivae, with the major complications of infertility and chronic pelvic pain, and blindness, respectively. Inflammation must, therefore, be tightly regulated to …

Sleep Deprivation And Neurological Disorders, Muhammed Bishir, Abid Bhat, Musthafa Mohamed Essa, Okobi Ekpo, Amadi O. Ihunwo, Vishnu Priya Veeraraghavan, Surapaneni Krishna Mohan, Arehally M. Mahalakshmi, Bipul Ray, Sunanda Tuladhar, Sulie Chang, Saravana Babu Chidambaram, Meena Kishore Sakharkar, Gilles J. Guillemin, M. Walid Qoronfleh, David M. Ojcius

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Sleep plays an important role in maintaining neuronal circuitry, signalling and helps maintain overall health and wellbeing. Sleep deprivation (SD) disturbs the circadian physiology and exerts a negative impact on brain and behavioural functions. SD impairs the cellular clearance of misfolded neurotoxin proteins like α-synuclein, amyloid-β, and tau which are involved in major neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. In addition, SD is also shown to affect the glymphatic system, a glial-dependent metabolic waste clearance pathway, causing accumulation of misfolded faulty proteins in synaptic compartments resulting in cognitive decline. Also, SD affects the immunological and redox system resulting …

Effects Of Electronic Cigarette Aerosol Exposure On Oral And Systemic Health, Cássio Luiz Coutinho Almeida-Da-Silva, Harmony Matshik Dakafay, Kenji O'Brien, Dallin Montierth, Nan Xiao, David M. Ojcius

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Conventional cigarette smoke harms nearly every organ of the body and is the leading cause of death in the United States and in the world. Decades of research have associated conventional cigarette smoke with several diseases and death. Heavily marketed, electronic nicotine delivery systems such as electronic cigarettes (e-cigarettes) are available in a variety of flavors and high nicotine concentrations. In 2019, a severe lung disease outbreak linked to e-cigarette use led to several deaths, which was called electronic-cigarette or vaping product use-associated lung injury (EVALI). Even though the trend of e-cigarette use among teens continues to increase, information on …