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JOURNAL ARTICLE
Sakshi Gera, Damini Sant, Shozeb Haider, Funda Korkmaz, Tan-Chun Kuo, Mehr Mathew, Helena Perez-Pena, Honglin Xie, Hao Chen, Rogerio Batista, Kejun Ma, Zhen Cheng, Elina Hadelia, Cemre Robinson, Anne Macdonald, Sari Miyashita, Anthony Williams, Gregory Jebian, Hirotaka Miyashita, Anisa Gumerova, Kseniia Ievleva, Pinar Smith, Jiahuan He, Vitaly Ryu, Victoria DeMambro, Matthew A Quinn, Marcia Meseck, Se-Min Kim, T Rajendra Kumar, Jameel Iqbal, Maria I New, Daria Lizneva, Clifford J Rosen, Aaron J Hsueh, Tony Yuen, Mone Zaidi
Blocking the action of FSH genetically or pharmacologically in mice reduces body fat, lowers serum cholesterol, and increases bone mass, making an anti-FSH agent a potential therapeutic for three global epidemics: obesity, osteoporosis, and hypercholesterolemia. Here, we report the generation, structure, and function of a first-in-class, fully humanized, epitope-specific FSH blocking antibody with a K D of 7 nM. Protein thermal shift, molecular dynamics, and fine mapping of the FSH-FSH receptor interface confirm stable binding of the Fab domain to two of five receptor-interacting residues of the FSHβ subunit, which is sufficient to block its interaction with the FSH receptor...
November 17, 2020: Proceedings of the National Academy of Sciences of the United States of America
#2
REVIEW
Jeanne Carter, Helen Q Huang, Jane Armer, Jay W Carlson, Suzy Lockwood, Susan Nolte, James Kauderer, Alan Hutson, Joan L Walker, Aimee C Fleury, Albert Bonebrake, John T Soper, Cara Mathews, Oliver Zivanovic, William Edward Richards, Annie Tan, David S Alberts, Richard R Barakat, Lari B Wenzel
OBJECTIVE: To assess quality of life (QOL) in patients who developed lower-extremity lymphedema (LLE) after radical gynecologic cancer surgery on prospective clinical trial GOG 244. METHODS: The prospective, national, cooperative group trial GOG-0244 determined the incidence of LLE and risk factors for LLE development, as well as associated impacts on QOL, in newly diagnosed patients undergoing surgery for endometrial, cervical, or vulvar cancer from 6/4/2012-11/17/2014...
January 2021: Gynecologic Oncology
#3
JOURNAL ARTICLE
Haoxiang Chang, Anshuman Sewda, Carla Marquez-Luna, Sierra R White, Bridget M Whitney, Jessica Williams-Nguyen, Robin M Nance, Won Jun Lee, Mari M Kitahata, Michael S Saag, Amanda Willig, Joseph J Eron, W Christopher Mathews, Peter W Hunt, Richard D Moore, Allison Webel, Kenneth H Mayer, Joseph A Delaney, Paul K Crane, Heidi M Crane, Ke Hao, Inga Peter
BACKGROUND: Advances in antiretroviral therapies have greatly improved the survival of people living with human immunodeficiency virus (HIV) infection (PLWH); yet, PLWH have a higher risk of cardiovascular disease than those without HIV. While numerous genetic loci have been linked to cardiometabolic risk in the general population, genetic predictors of the excessive risk in PLWH are largely unknown. METHODS: We screened for common and HIV-specific genetic variants associated with variation in lipid levels in 6284 PLWH (3095 European Americans [EA] and 3189 African Americans [AA]), from the Centers for AIDS Research Network of Integrated Clinical Systems cohort...
October 28, 2020: BMC Medicine
#4
JOURNAL ARTICLE
Lauren A Eaves, Hang T Nguyen, Julia E Rager, Kenneth G Sexton, Thomas Howard, Lisa Smeester, Anastasia N Freedman, Kjersti M Aagaard, Cynthia Shope, Barry Lefer, James H Flynn, Mathew H Erickson, Rebecca C Fry, William Vizuete
Atmospheric pollution represents a complex mixture of air chemicals that continually interact and transform, making it difficult to accurately evaluate associated toxicity responses representative of real-world exposure. This study leveraged data from a previously published article and reevaluated lung cell transcriptional response induced by outdoor atmospheric pollution mixtures using field-based exposure conditions in the industrialized Houston Ship Channel. The tested hypothesis was that individual and co-occurring chemicals in the atmosphere relate to altered expression of critical genes involved in inflammation and cancer-related processes in lung cells...
October 16, 2020: Environmental Science & Technology
#5
REVIEW
Alan Vainrib, Daniele Massera, Mark V Sherrid, Daniel G Swistel, Daniel Bamira, Homam Ibrahim, Cezar Staniloae, Mathew R Williams, Muhamed Saric
Left ventricular outflow tract (LVOT) obstruction in hypertrophic cardiomyopathy (HCM) is often caused by systolic anterior motion (SAM) of the mitral valve caused by the interplay between increased left ventricular (LV) wall thickness and an abnormal mitral valve anatomy and geometry. Three-dimensional (3D) echocardiographic imaging of the mitral valve has revolutionized the practice of cardiology, paving the way for new methods to see and treat valvular heart disease. Here we present the novel and incremental value of 3D transesophageal echocardiography (TEE) of SAM visualization...
January 2021: Journal of the American Society of Echocardiography
#6
JOURNAL ARTICLE
Edgar Simulundu, Francis Mupeta, Pascalina Chanda-Kapata, Ngonda Saasa, Katendi Changula, Walter Muleya, Simbarashe Chitanga, Miniva Mwanza, Paul Simusika, Herman Chambaro, Benjamin Mubemba, Masahiro Kajihara, Duncan Chanda, Lloyd Mulenga, Sombo Fwoloshi, Aaron Lunda Shibemba, Fred Kapaya, Paul Zulu, Kunda Musonda, Mwaka Monze, Nyambe Sinyange, Mazyanga L Mazaba, Muzala Kapin'a, Peter J Chipimo, Raymond Hamoonga, Davie Simwaba, William Ngosa, Albertina N Morales, Nkomba Kayeyi, John Tembo, Mathew Bates, Yasuko Orba, Hirofumi Sawa, Ayato Takada, King S Nalubamba, Kennedy Malama, Victor Mukonka, Alimuddin Zumla, Nathan Kapata
Since its first discovery in December 2019 in Wuhan, China, COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread rapidly worldwide. While African countries were relatively spared initially, the initial low incidence of COVID-19 cases was not sustained for long due to continuing travel links between China, Europe and Africa. In preparation, Zambia had applied a multisectoral national epidemic disease surveillance and response system resulting in the identification of the first case within 48 h of the individual entering the country by air travel from a trip to France...
January 2021: International Journal of Infectious Diseases: IJID
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JOURNAL ARTICLE
B Joseph Elmunzer, Rebecca L Spitzer, Lydia D Foster, Ambreen A Merchant, Eric F Howard, Vaishali A Patel, Mary K West, Emad Qayed, Rosemary Nustas, Ali Zakaria, Marc S Piper, Jason R Taylor, Lujain Jaza, Nauzer Forbes, Millie Chau, Luis F Lara, Georgios I Papachristou, Michael L Volk, Liam G Hilson, Selena Zhou, Vladimir M Kushnir, Alexandria M Lenyo, Caroline G McLeod, Sunil Amin, Gabriela N Kuftinec, Dhiraj Yadav, Charlie Fox, Jennifer M Kolb, Swati Pawa, Rishi Pawa, Andrew Canakis, Christopher Huang, Laith H Jamil, Andrew M Aneese, Benita K Glamour, Zachary L Smith, Katherine A Hanley, Jordan Wood, Harsh K Patel, Janak N Shah, Emil Agarunov, Amrita Sethi, Evan L Fogel, Gail McNulty, Abdul Haseeb, Judy A Trieu, Rebekah E Dixon, Jeong Yun Yang, Robin B Mendelsohn, Delia Calo, Olga C Aroniadis, Joseph F LaComb, James M Scheiman, Bryan G Sauer, Duyen T Dang, Cyrus R Piraka, Eric D Shah, Heiko Pohl, William M Tierney, Stephanie Mitchell, Ashwinee Condon, Adrienne Lenhart, Kulwinder S Dua, Vikram S Kanagala, Ayesha Kamal, Vikesh K Singh, Maria Ines Pinto-Sanchez, Joy M Hutchinson, Richard S Kwon, Sheryl J Korsnes, Harminder Singh, Zahra Solati, Field F Willingham, Patrick S Yachimski, Darwin L Conwell, Evan Mosier, Mohamed Azab, Anish Patel, James Buxbaum, Sachin Wani, Amitabh Chak, Amy E Hosmer, Rajesh N Keswani, Christopher J DiMaio, Michael S Bronze, Raman Muthusamy, Marcia I Canto, V Mihajlo Gjeorgjievski, Zaid Imam, Fadi Odish, Ahmed I Edhi, Molly Orosey, Abhinav Tiwari, Soumil Patwardhan, Nicholas G Brown, Anish A Patel, Collins O Ordiah, Ian P Sloan, Lilian Cruz, Casey L Koza, Uchechi Okafor, Thomas Hollander, Nancy Furey, Olga Reykhart, Natalia H Zbib, John A Damianos, James Esteban, Nick Hajidiacos, Melissa Saul, Melanie Mays, Gulsum Anderson, Kelley Wood, Laura Mathews, Galina Diakova, Molly Caisse, Lauren Wakefield, Haley Nitchie, Akbar K Waljee, Weijing Tang, Yueyang Zhang, Ji Zhu, Amar R Deshpande, Don C Rockey, Teldon B Alford, Valerie Durkalski
BACKGROUND & AIMS: The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. METHODS: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were abstracted manually from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations...
July 2021: Clinical Gastroenterology and Hepatology
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JOURNAL ARTICLE
Srividya B Balachander, Steven W Criscione, Kate F Byth, Justin Cidado, Ammar Adam, Paula Lewis, Terry Macintyre, Shenghua Wen, Deborah Lawson, Kathleen Burke, Tristan Lubinski, Jeffrey W Tyner, Stephen E Kurtz, Shannon K McWeeney, Jeffrey Varnes, R Bruce Diebold, Thomas Gero, Stephanos Ioannidis, Edward J Hennessy, William McCoull, Jamal C Saeh, Areya Tabatabai, Omid Tavana, Nancy Su, Alwin Schuller, Mathew J Garnett, Patricia Jaaks, Elizabeth A Coker, Gareth P Gregory, Andrea Newbold, Ricky W Johnstone, Eric Gangl, Martin Wild, Michael Zinda, J Paul Secrist, Barry R Davies, Stephen E Fawell, Francis D Gibbons
PURPOSE: Targeting Bcl-2 family members upregulated in multiple cancers has emerged as an important area of cancer therapeutics. While venetoclax, a Bcl-2-selective inhibitor, has had success in the clinic, another family member, Bcl-xL , has also emerged as an important target and as a mechanism of resistance. Therefore, we developed a dual Bcl-2/Bcl-xL inhibitor that broadens the therapeutic activity while minimizing Bcl-xL -mediated thrombocytopenia. EXPERIMENTAL DESIGN: We used structure-based chemistry to design a small-molecule inhibitor of Bcl-2 and Bcl-xL and assessed the activity against in vitro cell lines, patient samples, and in vivo models...
December 15, 2020: Clinical Cancer Research
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JOURNAL ARTICLE
Sophie Flack-Prain, Patrick Meir, Yadvinder Malhi, Thomas Luke Smallman, Mathew Williams
Leaf-area-index (LAI) underpins terrestrial ecosystem functioning, yet our ability to predict LAI remains limited. Across Amazon forests, mean LAI, LAI seasonal dynamics, and leaf-traits vary with soil moisture-stress. We hypothesise that LAI variation can be predicted via an optimality-based approach, using net canopy C-export (NCE, photosynthesis minus the C-cost of leaf growth and maintenance) as a fitness proxy. We applied a process-based terrestrial ecosystem model to seven plots across a moisture-stress gradient with detailed in-situ measurements, to determine nominal plant C-budgets...
September 26, 2020: Global Change Biology
#10
JOURNAL ARTICLE
Philippe M Burlina, Neil J Joshi, Phil A Mathew, William Paul, Alison W Rebman, John N Aucott
This study examines the use of AI methods and deep learning (DL) for prescreening skin lesions and detecting the characteristic erythema migrans rash of acute Lyme disease. Accurate identification of erythema migrans allows for early diagnosis and treatment, which avoids the potential for later neurologic, rheumatologic, and cardiac complications of Lyme disease. We develop and test several deep learning models for detecting erythema migrans versus several other clinically relevant skin conditions, including cellulitis, tinea corporis, herpes zoster, erythema multiforme, lesions due to tick bites and insect bites, as well as non-pathogenic normal skin...
October 2020: Computers in Biology and Medicine
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JOURNAL ARTICLE
Farina J Mahmud, Yong Du, Elizabeth Greif, Thomas Boucher, Robert F Dannals, William B Mathews, Martin G Pomper, Polina Sysa-Shah, Kelly A Metcalf Pate, Claire Lyons, Bess Carlson, Maria Chacona, Amanda M Brown
BACKGROUND: Osteopontin (OPN) as a secreted signaling protein is dramatically induced in response to cellular injury and neurodegeneration. Microglial inflammatory responses in the brain are tightly associated with the neuropathologic hallmarks of neurodegenerative disease, but understanding of the molecular mechanisms remains in several contexts poorly understood. METHODS: Micro-positron emission tomography (PET) neuroimaging using radioligands to detect increased expression of the translocator protein (TSPO) receptor in the brain is a non-invasive tool used to track neuroinflammation in living mammals...
September 17, 2020: Journal of Neuroinflammation
#12
JOURNAL ARTICLE
Jonathan D Harper, Ian Metzler, Michael Kennedy Hall, Tony T Chen, Adam D Maxwell, Bryan W Cunitz, Barbrina Dunmire, Jeff Thiel, James C Williams, Michael R Bailey, Mathew D Sorensen
Purpose: To test the effectiveness (Participant A) and tolerability (Participant B) of urinary stone comminution in the first-in-human trial of a new technology, burst-wave lithotripsy (BWL). Materials and Methods: An investigational BWL and ultrasonic propulsion system was used to target a 7-mm kidney stone in the operating room before ureteroscopy (Participant A). The same system was used to target a 7.5 mm ureterovesical junction stone in clinic without anesthesia (Participant B). Results: For Participant A, a ureteroscope inserted after 9 minutes of BWL observed fragmentation of the stone to <2 mm fragments...
April 2021: Journal of Endourology
#13
JOURNAL ARTICLE
David J Weber, Thomas R Talbot, Allison Weinmann, Trini Mathew, Emily Heil, Edward Stenehjem, Robert Duncan, Alan Gross, Patricia Stinchfield, Christopher Baliga, Jamie Wagner, William Schaffner, Kelly Echevarria, Marci Drees
SHEA endorses adhering to the recommendations by the CDC and ACIP for immunizations of all children and adults. All persons providing clinical care should be familiar with these recommendations and should routinely assess immunization compliance of their patients and strongly recommend all routine immunizations to patients. All healthcare personnel (HCP) should be immunized against vaccine-preventable diseases as recommended by the CDC/ACIP (unless immunity is demonstrated by another recommended method). SHEA endorses the policy that immunization should be a condition of employment or functioning (students, contract workers, volunteers, etc) at a healthcare facility...
January 2021: Infection Control and Hospital Epidemiology
#14
JOURNAL ARTICLE
Ying-Ying Leung, Richard Holland, Ashish J Mathew, Christine Lindsay, Niti Goel, Alexis Ogdie, Ana-Maria Orbai, Pil Hojgaard, Jeffrey Chau, Laura C Coates, Vibeke Strand, Dafna D Gladman, Robin Christensen, William Tillett, Philip Mease
OBJECTIVES: Physical function (PF) is a core domain to be measured in randomized controlled trials (RCTs) of psoriatic arthritis (PsA), yet the discriminative performance of patient reported outcome measures (PROMs) for PF in RCTs has not been evaluated systematically. In this systematic review, we aimed to evaluate the clinical trial discrimination of PF-PROMs in PsA RCTs. METHODS: We searched PubMed and Scopus databases in English to identify all original RCTs on biological and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) conducted in PsA...
October 2020: Seminars in Arthritis and Rheumatism
#15
MULTICENTER STUDY
Galina M Hayes, Alexa M Bersenas, Karol Mathews, William G Lane, Denise F LaLonde-Paul, Andrea Steele, Ana Avellaneda
OBJECTIVE: To investigate associations among care errors, staffing, and workload in small animal ICUs. DESIGN: Multicenter observational cohort study conducted between January 2017 and September 2018. SETTING: Three small animal teaching hospital ICUs. ANIMALS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on patient numbers, illness severity (assesed via the acute patient physiologic and laboratory evaluation [APPLE] score), care burden, staffing levels, technician experience/education level, and care errors were collected at each study site...
September 2020: Journal of Veterinary Emergency and Critical Care
#16
JOURNAL ARTICLE
William Small, Walter R Bosch, Mathew M Harkenrider, Jonathan B Strauss, Nadeem Abu-Rustum, Kevin V Albuquerque, Sushil Beriwal, Carien L Creutzberg, Patricia J Eifel, Beth A Erickson, Anthony W Fyles, Courtney L Hentz, Anuja Jhingran, Ann H Klopp, Charles A Kunos, Loren K Mell, Lorraine Portelance, Melanie E Powell, Akila N Viswanathan, Joseph H Yacoub, Catheryn M Yashar, Kathryn A Winter, David K Gaffney
PURPOSE: Accurate target definition is critical for the appropriate application of radiation therapy. In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to define the clinical target volume (CTV) for intensity modulated pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. The current project is an updated consensus of CTV definitions, with removal of all references to bony landmarks and inclusion of the para-aortic and inferior obturator nodal regions...
February 1, 2021: International Journal of Radiation Oncology, Biology, Physics
#17
JOURNAL ARTICLE
Frederick J Kohlhapp, Dipica Haribhai, Rebecca Mathew, Ryan Duggan, Paul A Ellis, Rui Wang, Elisabeth A Lasater, Yan Shi, Nimita Dave, Jacob J Riehm, Valerie A Robinson, An D Do, Yijin Li, Christine J Orr, Deepak Sampath, Aparna Raval, Mark Merchant, Anahita Bhathena, Ahmed Hamed Salem, Keith M Hamel, Joel D Leverson, Cherrie Donawho, William N Pappano, Tamar Uziel
The antiapoptotic protein BCL2 plays critical roles in regulating lymphocyte development and immune responses, and has also been implicated in tumorigenesis and tumor survival. However, it is unknown whether BCL2 is critical for antitumor immune responses. We evaluated whether venetoclax, a selective small-molecule inhibitor of BCL2, would influence the antitumor activity of immune checkpoint inhibitors (ICI). We demonstrate in mouse syngeneic tumor models that venetoclax can augment the antitumor efficacy of ICIs accompanied by the increase of PD-1+ T effector memory cells...
January 2021: Cancer Discovery
#18
JOURNAL ARTICLE
Philippe Burlina, William Paul, Philip Mathew, Neil Joshi, Katia D Pacheco, Neil M Bressler
Importance: Recent studies have demonstrated the successful application of artificial intelligence (AI) for automated retinal disease diagnostics but have not addressed a fundamental challenge for deep learning systems: the current need for large, criterion standard-annotated retinal data sets for training. Low-shot learning algorithms, aiming to learn from a relatively low number of training data, may be beneficial for clinical situations involving rare retinal diseases or when addressing potential bias resulting from data that may not adequately represent certain groups for training, such as individuals older than 85 years...
October 1, 2020: JAMA Ophthalmology
#19
JOURNAL ARTICLE
Eleanor C Warren, Stephanie Dooves, Eleonora Lugarà, Joseph Damstra-Oddy, Judith Schaf, Vivi M Heine, Mathew C Walker, Robin S B Williams
Low-glucose and -insulin conditions, associated with ketogenic diets, can reduce the activity of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, potentially leading to a range of positive medical and health-related effects. Here, we determined whether mTORC1 signaling is also a target for decanoic acid, a key component of the medium-chain triglyceride (MCT) ketogenic diet. Using a tractable model system, Dictyostelium , we show that decanoic acid can decrease mTORC1 activity, under conditions of constant glucose and in the absence of insulin, measured by phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1)...
September 22, 2020: Proceedings of the National Academy of Sciences of the United States of America
#20
JOURNAL ARTICLE
Mathew William Hill, Michael Joseph Duncan, Michael James Price
The purpose of the present study was to quantify differences in lower extremity reach performance, static posturography and gait outcomes between young (20-39 years), middle-aged (40-59 years) and older (60-79 years) adults using identical tests and parameters. This was a cross-sectional study with three parallel groups (young [20-39 years] vs. intermediate [40-59 years] vs. older [60-79 years] adults). In a randomised order each participant completed: (i) static posturography, (ii) lower extremity reach performance, and (iii) gait assessment...
October 15, 2020: Experimental Gerontology
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