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JOURNAL ARTICLE
Mark E Alexander, Russell Gongwer, Felicia L Trachtenberg, L LuAnn Minich, John K Triedman, Jonathan R Kaltman, Richard J Czosek, Martin Tristani-Firouzi, Martin J LaPage, Sabrina S Tsao, Andrew E Radbill, Michael P DiLorenzo, Joshua R Kovach, Elizabeth A Stephenson, Christopher Janson, Chad Mao, Jack C Salerno, Bradley C Clark, Joseph Mahgerefteh, Thomas Pilcher, Tiffanie R Johnson, Jeff J Kim, Santiago O Valdes, Nicole Cain, Lanier Jackson, Elizabeth V Saarel
Pediatric ECG standards have been defined without echocardiographic confirmation of normal anatomy. The Pediatric Heart Network Normal Echocardiogram Z-score Project provides a racially diverse group of healthy children with normal echocardiograms. We hypothesized that ECG and echocardiographic measures of left ventricular (LV) dimensions are sufficiently correlated in healthy children to imply a clinically meaningful relationship. This was a secondary analysis of a previously described cohort including 2170 digital ECGs...
March 23, 2024: Pediatric Cardiology
#22
Rodolpho S A de Carvalho, Md Shamiul I Rasel, Nitesh K Khandelwal, Thomas M Tomasiak
Many ATP-binding cassette (ABC) transporters are regulated by phosphorylation on long and disordered loops. which makes their interactions a challenge to visualize. We have trapped an activated state of the regulatory domain (R-domain) of Yeast Cadmium Factor 1 (Ycf1) by enzymatically enriching the phosphorylated state. A 3.2 Å cryo-EM structure reveals an R-domain structure with four phosphorylated residues and a position for the entire R-domain. The structure reveals key R-domain interactions including a bridging interaction between NBD1 and NBD2 as well as an interaction the R-insertion, another regulatory region...
March 6, 2024: bioRxiv
#23
JOURNAL ARTICLE
Michael S Haney, Róbert Pálovics, Christy Nicole Munson, Chris Long, Patrik K Johansson, Oscar Yip, Wentao Dong, Eshaan Rawat, Elizabeth West, Johannes C M Schlachetzki, Andy Tsai, Ian Hunter Guldner, Bhawika S Lamichhane, Amanda Smith, Nicholas Schaum, Kruti Calcuttawala, Andrew Shin, Yung-Hua Wang, Chengzhong Wang, Nicole Koutsodendris, Geidy E Serrano, Thomas G Beach, Eric M Reiman, Christopher K Glass, Monther Abu-Remaileh, Annika Enejder, Yadong Huang, Tony Wyss-Coray
Several genetic risk factors for Alzheimer's disease implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells1 . However, the relationship between lipid metabolism in glia and Alzheimer's disease pathology remains poorly understood. Through single-nucleus RNA sequencing of brain tissue in Alzheimer's disease, we have identified a microglial state defined by the expression of the lipid droplet-associated enzyme ACSL1 with ACSL1-positive microglia being most abundant in patients with Alzheimer's disease having the APOE4/4 genotype...
March 13, 2024: Nature
#24
JOURNAL ARTICLE
Hannah Hartman-Houstman, Steve Swenson, Radu O Minea, Uttam K Sinha, Ming-Fu Chiang, Thomas C Chen, Axel H Schönthal
The Epstein-Barr virus (EBV) is accepted as a primary risk factor for certain nasopharyngeal carcinoma (NPC) subtypes, where the virus persists in a latent stage which is thought to contribute to tumorigenesis. Current treatments are sub-optimal, and recurrence occurs in many cases. An alternative therapeutic concept is aimed at triggering the lytic cycle of EBV selectively in tumor cells as a means to add clinical benefit. While compounds able to stimulate the lytic cascade have been identified, their clinical application so far has been limited...
February 26, 2024: Cancers
#25
JOURNAL ARTICLE
Thomas A Kite, Alexander Chase, Colum G Owens, Aadil Shaukat, Abdul M Mozid, Peter O'Kane, Helen Routledge, Divaka Perera, Ajay K Jain, Nick Palmer, Stephen P Hoole, Mohaned Egred, Manas K Sinha, Thomas J Cahill, Brijesh Anantharam, Jonathan Byrne, Paul D Morris, Sharon Kean, Ahmed Sabra, Muhammad Aetesam-Ur-Rahman, Jonathan Mailey, Ozan Demir, Kyriacos Mouyis, Ahmed Abdalwahab, Dimitrios Terentes-Printzios, Ritesh Kanyal, Nick Curzen, Colin Berry, Anthony H Gershlick, Andrew Ladwiniec
OBJECTIVES: Cardiac surgery for coronary artery disease was dramatically reduced during the first wave of the COVID-19 pandemic. Many patients with disease ordinarily treated with coronary artery bypass grafting (CABG) instead underwent percutaneous coronary intervention (PCI). We sought to describe 12-month outcomes following PCI in patients who would typically have undergone CABG. METHODS: Between March 1 and July 31, 2020, patients who received revascularization with PCI when CABG would have been the primary choice of revascularization were enrolled in the prospective, multicenter UK-ReVasc Registry...
March 6, 2024: Journal of Invasive Cardiology
#26
JOURNAL ARTICLE
Monique A Wyatt, Emily E Pisarski, Alisaati Nalumansi, Vicent Kasiita, Brenda Kamusiime, Grace K Nalukwago, Dorothy Thomas, Timothy R Muwonge, Andrew Mujugira, Renee Heffron, Norma C Ware
Tailored delivery strategies are important for optimizing the benefit and overall reach of PrEP in sub-Saharan Africa. An integrated approach of delivering time-limited PrEP in combination with ART to serodifferent couples encourages PrEP use in the HIV-negative partner as a bridge to sustained ART use. Although PrEP has been delivered in ART clinics for many years, the processes involved in integrating PrEP into ART services are not well understood. The Partners PrEP Program was a stepped-wedge cluster randomized trial of integrated PrEP and ART delivery for HIV serodifferent couples in 12 public health facilities in central Uganda (Clinicaltrials...
2024: PLOS Glob Public Health
#27
REVIEW
Prashant Kumar, Sisay E Debele, Soheila Khalili, Christos H Halios, Jeetendra Sahani, Nasrin Aghamohammadi, Maria de Fatima Andrade, Maria Athanassiadou, Kamaldeep Bhui, Nerea Calvillo, Shi-Jie Cao, Frederic Coulon, Jill L Edmondson, David Fletcher, Edmilson Dias de Freitas, Hai Guo, Matthew C Hort, Madhusudan Katti, Thomas Rodding Kjeldsen, Steffen Lehmann, Giuliano Maselli Locosselli, Shelagh K Malham, Lidia Morawska, Rajan Parajuli, Christopher D F Rogers, Runming Yao, Fang Wang, Jannis Wenk, Laurence Jones
The combination of urbanization and global warming leads to urban overheating and compounds the frequency and intensity of extreme heat events due to climate change. Yet, the risk of urban overheating can be mitigated by urban green-blue-grey infrastructure (GBGI), such as parks, wetlands, and engineered greening, which have the potential to effectively reduce summer air temperatures. Despite many reviews, the evidence bases on quantified GBGI cooling benefits remains partial and the practical recommendations for implementation are unclear...
March 4, 2024: The innovation
#28
JOURNAL ARTICLE
Sarah Spencer, Julia Lukewich, Emily Gard Marshall, Maria Mathews, Shabnam Asghari, Judith B Brown, Thomas R Freeman, Paul Gill, Samina Idrees, Rita K McCracken, Sudit Ranade, Steve Slade, Amanda L Terry, Jamie Wickett, Eric Wong, Richard Buote, Leslie Meredith, Lauren Moritz, Dana Ryan, Lindsay Hedden
BACKGROUND: Family physicians (FPs) fill an essential role in public health emergencies yet have frequently been neglected in pandemic response plans. This exclusion harms FPs in their clinical roles and has unintended consequences in the management of concurrent personal responsibilities, many of which were amplified by the pandemic. The objective of our study was to explore the experiences of FPs during the first year of the COVID-19 pandemic to better understand how they managed their competing professional and personal priorities...
March 4, 2024: Human Resources for Health
#29
JOURNAL ARTICLE
Mohit K Turagam, Petr Neuzil, Boris Schmidt, Tobias Reichlin, Kars Neven, Andreas Metzner, Jim Hansen, Yuri Blaauw, Philippe Maury, Thomas Arentz, Philipp Sommer, Ante Anic, Frederic Anselme, Serge Boveda, Tom Deneke, Stephan Willems, Pepijn van der Voort, Roland Tilz, Moritoshi Funasako, Daniel Scherr, Reza Wakili, Daniel Steven, Josef Kautzner, Johan Vijgen, Pierre Jais, Jan Petru, Julian Chun, Laurent Roten, Anna Füting, Marc D Lemoine, Martin Ruwald, Bart A Mulder, Anne Rollin, Heiko Lehrmann, Thomas Fink, Zrinka Jurisic, Corentin Chaumont, Raquel Adelino, Karin Nentwich, Melanie Gunawardene, Alexandre Ouss, Christian-Hendrik Heeger, Martin Manninger, Jan-Eric Bohnen, Arian Sultan, Petr Peichl, Pieter Koopman, Nicolas Derval, Thomas Kueffer, Nico Reinsch, Vivek Y Reddy
BACKGROUND: Pulmonary vein isolation (PVI) alone is insufficient to treat many patients with persistent atrial fibrillation (PersAF). Adjunctive left atrial posterior wall (LAPW) ablation with thermal technologies has revealed lack of efficacy, perhaps limited by the difficulty in achieving lesion durability amid concerns of esophageal injury. OBJECTIVES: This study aims to compare the safety and effectiveness of PVI + LAPW ablation vs PVI in patients with PersAF using pulsed-field ablation (PFA)...
January 31, 2024: JACC. Clinical Electrophysiology
#30
JOURNAL ARTICLE
Emily C Fogarty, Matthew S Schechter, Karen Lolans, Madeline L Sheahan, Iva Veseli, Ryan M Moore, Evan Kiefl, Thomas Moody, Phoebe A Rice, Michael K Yu, Mark Mimee, Eugene B Chang, Hans-Joachim Ruscheweyh, Shinichi Sunagawa, Sandra L Mclellan, Amy D Willis, Laurie E Comstock, A Murat Eren
Plasmids are extrachromosomal genetic elements that often encode fitness-enhancing features. However, many bacteria carry "cryptic" plasmids that do not confer clear beneficial functions. We identified one such cryptic plasmid, pBI143, which is ubiquitous across industrialized gut microbiomes and is 14 times as numerous as crAssphage, currently established as the most abundant extrachromosomal genetic element in the human gut. The majority of mutations in pBI143 accumulate in specific positions across thousands of metagenomes, indicating strong purifying selection...
February 29, 2024: Cell
#31
JOURNAL ARTICLE
Enrico Pirotta, Peter L Tyack, John W Durban, Holly Fearnbach, Philip K Hamilton, Catriona M Harris, Amy R Knowlton, Scott D Kraus, Carolyn A Miller, Michael J Moore, Heather M Pettis, Theoni Photopoulou, Rosalind M Rolland, Robert S Schick, Len Thomas
Body size is key to many life-history processes, including reproduction. Across species, climate change and other stressors have caused reductions in the body size to which animals can grow, called asymptotic size, with consequences for demography. A reduction in mean asymptotic length was documented for critically endangered North Atlantic right whales, in parallel with declines in health and vital rates resulting from human activities and environmental changes. Here, we tested whether smaller body size was associated with lower reproductive output, using a state-space model for individual health, survival and reproduction that quantifies the mechanistic links between these processes...
February 2024: Royal Society Open Science
#32
JOURNAL ARTICLE
Rukundo K Benedict, Thomas W Pullum, Sara Riese, Erin Milner
Anemia is a significant public health problem in many low- and middle-income countries (LMICs), with young children being especially vulnerable. Iron deficiency is a leading cause of anemia and prior studies have shown associations between low iron status/iron deficiency anemia and poor child development outcomes. In LMICs, 43% of children under the age of five years are at risk of not meeting their developmental potential. However, few studies have examined associations between anemia status and early childhood development (ECD) in large population-based surveys...
2024: PloS One
#33
Rajendra Kumar, Janet Mendonca, Abhishek Shetty, Yuhan Yang, Olutosin Owoyemi, Lillian Wilson, Kavya Boyapati, Deven Topiwala, Naiju Thomas, Huong Nguyen, Jun Luo, Channing J Paller, Samuel Denmeade, Michael A Carducci, Sushant K Kachhap
Among the known nuclear exportins, CRM1 is the most studied prototype. Dysregulation of CRM1 occurs in many cancers, hence, understanding the role of CRM1 in cancer can help in developing synergistic therapeutics. The study investigates how CRM1 affects prostate cancer growth and survival. It examines the role of CRM1 in regulating androgen receptor (AR) and DNA repair in prostate cancer. Our findings reveal that CRM1 influences AR mRNA and protein stability, leading to a loss of AR protein upon CRM1 inhibition...
February 16, 2024: bioRxiv
#34
JOURNAL ARTICLE
Zhongchao Wang, Emily J Camm, Anna Maria Nuzzo, Ana-Mishel Spiroski, Katie L Skeffington, Thomas J Ashmore, Alessandro Rolfo, Tullia Todros, Angela Logan, Jin Ma, Michael P Murphy, Youguo Niu, Dino A Giussani
Gestational hypoxia adversely affects uterine artery function, increasing complications. However, an effective therapy remains unidentified. Here, we show in rodent uterine arteries that hypoxic pregnancy promotes hypertrophic remodelling, increases constrictor reactivity via protein kinase C signalling, and triggers compensatory dilatation via nitric oxide-dependent mechanisms and stimulation of large conductance Ca2+ -activated K+ -channels. Maternal in vivo oral treatment with the mitochondria-targeted antioxidant MitoQ in hypoxic pregnancy normalises uterine artery reactivity and prevents vascular remodelling...
February 21, 2024: Journal of Physiology
#35
JOURNAL ARTICLE
Katharina Wørzner, Julie Zimmermann, Regitze Buhl, Anna Desoi, Dennis Christensen, Jes Dietrich, Nina Dieu Nhien Tran Nguyen, Thomas Lindenstrøm, Joshua S Woodworth, Reham Sabah Alhakeem, Steven Yu, Niels Ødum, Rasmus Mortensen, Judith F Ashouri, Gabriel K Pedersen
In many autoimmune diseases, autoantigen-specific Th17 cells play a pivotal role in disease pathogenesis. Th17 cells can transdifferentiate into other T cell subsets in inflammatory conditions, however, there have been no attempts to target Th17 cell plasticity using vaccines. We investigated if autoantigen-specific Th17 cells could be specifically targeted using a therapeutic vaccine approach, where antigen was formulated in all-trans retinoic acid (ATRA)-containing liposomes, permitting co-delivery of antigen and ATRA to the same target cell...
February 19, 2024: Journal of Autoimmunity
#36
JOURNAL ARTICLE
Rebecca J Hall, Ann E Snaith, Matthew J N Thomas, Michael A Brockhurst, Alan McNally
Multidrug-resistant Escherichia coli is a leading cause of global mortality. Transfer of plasmids carrying genes encoding beta-lactamases, carbapenamases, and colistin resistance between lineages is driving the rising rates of hard-to-treat nosocomial and community infections. Multidrug resistance (MDR) plasmid acquisition commonly causes transcriptional disruption, and while a number of studies have shown strain-specific fitness and transcriptional effects of an MDR plasmid across diverse bacterial lineages, fewer studies have compared the impacts of different MDR plasmids in a common bacterial host...
February 20, 2024: MSystems
#37
JOURNAL ARTICLE
Victor Dinda, Andrew Nyerere Kimang'a, Daniel Kariuki, Anthony Wawire Sifuna, Thomas James O'Brien, Martin Welch, Oleg N Reva
OBJECTIVES: Klebsiella pneumoniae are a frequent cause of nosocomial infections worldwide. Sequence type 147 (ST147) has been reported as a major circulating high-risk lineage in many countries, and appears to be a formidable platform for the dissemination of antimicrobial resistance (AMR) determinants. However, the distribution of this pathogen in Western African hospitals has been scarcely studied. The main objective of this work was to perform whole genome sequencing of K. pneumoniae isolates from a referral hospital in Kakamega (Kenya) for genotyping and identification of AMR and virulence determinants...
2024: Access microbiology
#38
REVIEW
Christina C Chang, Thomas S Harrison, Tihana A Bicanic, Methee Chayakulkeeree, Tania C Sorrell, Adilia Warris, Ferry Hagen, Andrej Spec, Rita Oladele, Nelesh P Govender, Sharon C Chen, Christopher H Mody, Andreas H Groll, Yee-Chun Chen, Michail S Lionakis, Alexandre Alanio, Elizabeth Castañeda, Jairo Lizarazo, José E Vidal, Takahiro Takazono, Martin Hoenigl, Jan-Willem Alffenaar, Jean-Pierre Gangneux, Rajeev Soman, Li-Ping Zhu, Alexandro Bonifaz, Joseph N Jarvis, Jeremy N Day, Nikolai Klimko, Jon Salmanton-García, Grégory Jouvion, David B Meya, David Lawrence, Sebastian Rahn, Felix Bongomin, Brendan J McMullan, Rosanne Sprute, Tinashe K Nyazika, Justin Beardsley, Fabianne Carlesse, Christopher H Heath, Olusola O Ayanlowo, Olga M Mashedi, Flavio Queiroz-Telles Filho, Mina C Hosseinipour, Atul K Patel, Elvis Temfack, Nina Singh, Oliver A Cornely, David R Boulware, Olivier Lortholary, Peter G Pappas, John R Perfect
Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe...
February 9, 2024: Lancet Infectious Diseases
#39
JOURNAL ARTICLE
Pravesh Parekh, Chun Chieh Fan, Oleksandr Frei, Clare E Palmer, Diana M Smith, Carolina Makowski, John R Iversen, Diliana Pecheva, Dominic Holland, Robert Loughnan, Pierre Nedelec, Wesley K Thompson, Donald J Hagler, Ole A Andreassen, Terry L Jernigan, Thomas E Nichols, Anders M Dale
The linear mixed-effects model (LME) is a versatile approach to account for dependence among observations. Many large-scale neuroimaging datasets with complex designs have increased the need for LME; however LME has seldom been used in whole-brain imaging analyses due to its heavy computational requirements. In this paper, we introduce a fast and efficient mixed-effects algorithm (FEMA) that makes whole-brain vertex-wise, voxel-wise, and connectome-wide LME analyses in large samples possible. We validate FEMA with extensive simulations, showing that the estimates of the fixed effects are equivalent to standard maximum likelihood estimates but obtained with orders of magnitude improvement in computational speed...
February 1, 2024: Human Brain Mapping
#40
JOURNAL ARTICLE
Lindsey S Marmont, Anna K Orta, Becca W A Baileeves, David Sychantha, Ana Fernández-Galliano, Yancheng E Li, Neil G Greene, Robin A Corey, Phillip J Stansfeld, William M Clemons, Thomas G Bernhardt
Many bacterial surface glycans such as the peptidoglycan (PG) cell wall are built from monomeric units linked to a polyprenyl lipid carrier. How this limiting carrier is distributed among competing pathways has remained unclear. Here we describe the isolation of hyperactive variants of Pseudomonas aeruginosa MraY, the enzyme that forms the first lipid-linked PG precursor. These variants result in the elevated production of the final PG precursor lipid II in cells and are hyperactive in vitro. The activated MraY variants have substitutions that map to a cavity on the extracellular side of the dimer interface, far from the active site...
February 9, 2024: Nature Microbiology
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