Halogen Oxidation Reactions of (C5Ph5)Cr(CO)3 and Lewis Base Addition To [(C5Ph5)Cr(μ-X)X]2: Electrochemical, Magnetic, and Raman Spectroscopic Characterization of [(C5Ph5)CrX2]2 and (C5Ph5)CrX2(THF) (X = Cl, Br, I). X-ray Crystal Structure of [(C5Ph5)Cr(μ-Cl)Cl]2

The 17-electron complex (C5Ph5)Cr(CO)3 reacts with halogens (C6H5I•Cl2, Br2, and I2) in C6H6 to yield the dimeric oxidation products [(C5Ph5)Cr(m-X)X]2 as thermally stable solids. Reactions with other chlorinating agents similarly yield [(C5Ph5)CrCl2]2. An X-ray crystal structure of [(C5Ph5)Cr(m-Cl)Cl]2 was obtained. The magnetic properties of the Cl2 bridged dimer have been determined and modeled using the usual isotropic hamiltonian which yields J/k = –30 K. Low-temperature (77 K) Raman spectra of solid [(C5Ph5)CrX2]2 (X = Cl, I) allow assignments to be made for the metal-ring and metal halogen stretching modes in the low frequency region (\u3c 600 cm-1). Tetrahydrofuran (THF) cleaves these dimers to yield complexes of the form (C5Ph5)CrX2(THF)

Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis

The poorly studied picornavirus, human parechovirus 3 (HPeV3) causes neonatal sepsis with no therapies available. Our 4.3-Å resolution structure of HPeV3 on its own and at 15 Å resolution in complex with human monoclonal antibody Fabs demonstrates the expected picornavirus capsid structure with three distinct features. First, 25% of the HPeV3 RNA genome in 60 sites is highly ordered as confirmed by asymmetric reconstruction, and interacts with conserved regions of the capsid proteins VP1 and VP3. Second, the VP0 N terminus stabilizes the capsid inner surface, in contrast to other picornaviruses where on expulsion as VP4, it forms an RNA translocation channel. Last, VP1's hydrophobic pocket, the binding site for the antipicornaviral drug, pleconaril, is blocked and thus inappropriate for antiviral development. Together, these results suggest a direction for development of neutralizing antibodies, antiviral drugs based on targeting the RNA-protein interactions and dissection of virus assembly on the basis of RNA nucleation.Peer reviewe

Concepts in Animal Parasitology, Part 3: Endoparasitic Platyhelminths

Part III: Endoparasitic Platyhelminths, chapters 15-47, pages 231-532, in Concepts in Animal Parasitology. 2024. Scott L. Gardner and Sue Ann Gardner, editors. Zea Books, Lincoln, Nebraska, United States; part III doi: 10.32873/unl.dc.ciap073 Platyhelminthes Chapter 15: Introduction to Endoparasitic Platyhelminths (Phylum Platyhelminthes) by Larry S. Roberts, John J. Janovy, Jr., Steve Nadler, and Scott L. Gardner, pages 231-240 Cestoda Chapter 16: Introduction to Cestodes (Class Cestoda) by Scott L. Gardner, pages 241-246 Eucestoda Chapter 17: Introduction to Cyclophyllidea Beneden in Braun, 1900 (Order) by Scott L. Gardner, pages 247-250 Chapter 18: Taenia (Genus) by Sumiya Ganzorig and Scott. L. Gardner, pages 251-261 Chapter 19: Echinococcus (Genus) by Akira Ito and Scott. L. Gardner, pages 262-275 Chapter 20: Proteocephalidae La Rue, 1911 (Family) by Tomáš Scholz and Roman Kuchta, pages 276-282 Chapter 21: Bothriocephalidea Kuchta et al., 2008 (Order) by Jorge Falcón-Ordaz and Luis García-Prieto, pages 283-288 Chapter 22: Diphyllobothriidea Kuchta et al., 2008 (Order): The Broad Tapeworms by Tomáš Scholz and Roman Kuchta, pages 289-296 Chapter 23: Trypanorhyncha Diesing, 1863 (Order) by Francisco Zaragoza-Tapia and Scott Monks, pages 297-305 Chapter 24: Cathetocephalidea Schmidt and Beveridge, 1990 (Order) by Luis García-Prieto, Omar Lagunas-Calvo, Brenda Atziri García-García, and Berenice Adán-Torres, pages 306-309 Chapter 25: Diphyllidea van Beneden in Carus, 1863 (Order) by Luis García-Prieto, Brenda Atziri García-García, Omar Lagunas-Calvo, and Berenice Adán-Torres, pages 310-315 Chapter 26: Lecanicephalidea Hyman, 1951 (Order) by Luis García-Prieto, Berenice Adán-Torres, Omar Lagunas-Calvo, and Brenda Atziri García- García, pages 316-320 Chapter 27: Litobothriidea Dailey, 1969 (Order) by Luis García-Prieto, Berenice Adán-Torres, Brenda Atziri García-García, and Omar Lagunas-Calvo, pages 321-325 Chapter 28: Phyllobothriidea Caira et al., 2014 (Order) by Brenda Atziri García-García, Omar Lagunas-Calvo, Berenice Adán-Torres, and Luis García-Prieto, pages 326-331 Chapter 29: Rhinebothriidea Healy et al., 2009 (Order) by Omar Lagunas-Calvo, Brenda Atziri García-García, Berenice Adán-Torres, and Luis García-Prieto, pages 332-339 Chapter 30: Relics of “Tetraphyllidea” van Beneden, 1850 (Order) by Berenice Adán-Torres, Omar Lagunas-Calvo, Brenda Atziri García-García, and Luis García-Prieto, pages 340-346 Amphilinidea Chapter 31: Amphilinidea Poche 1922 (Order) by Klaus Rohde, pages 347-353 Gyrocotylidea Chapter 32: Gyrocotylidea (Order): The Most Primitive Group of Tapeworms by Willi E. R. Xylander and Klaus Rohde, pages 354-360 Trematoda Aspidogastrea Chapter 33: Aspidogastrea (Subclass) by Klaus Rohde, pages 361-377 Digenea: Diplostomida Chapter 34: Introduction to Diplostomida Olson et al., 2003 (Order) by Lucrecia Acosta Soto, Bernard Fried, and Rafael Toledo, pages 378-393 Chapter 35: Aporocotylidae (Family): Fish Blood Flukes by Russell Q.-Y. Yong, pages 394-401 Digenea: Plagiorchiida Chapter 36: Introduction to Plagiorchiida La Rue, 1957 (Order) by Rafael Toledo, Bernard Fried, and Lucrecia Acosta Soto, pages 402-404 Chapter 37: Bivesiculata Olson et al., 2003 (Suborder): Small, Rare, but Important by Thomas H. Cribb and Scott C. Cutmore, pages 405-408 Chapter 38: Echinostomata La Rue, 1926 (Suborder) by Rafael Toledo, Bernard Fried, and Lucrecia Acosta Soto, pages 409-422 Chapter 39: Haplosplanchnata Olson et al., 2003 (Suborder): Two Hosts with Half the Guts by Daniel C. Huston, pages 423-427 Chapter 40: Hemiurata Skrjabin & Guschanskaja, 1954 (Suborder) by Lucrecia Acosta Soto, Bernard Fried, and Rafael Toledo, pages 428-435 Chapter 41: Monorchiata Olson et al., 2003 (Suborder): Two Families Separated by Salinity by Nicholas Q.-X. Wee, pages 436-442 Chapter 42: Opisthorchis (Genus) compiled from material from the United States Centers for Disease Control and Prevention, Division of Parasitic Diseases and Malaria by Sue Ann Gardner, pages 443-445 Xiphidiata Chapter 43: Allocreadiidae Looss, 1902 (Family) by Gerardo Pérez-Ponce de León, David Iván Hernández-Mena, and Brenda Solórzano-García, pages 446-459 Chapter 44: Haematoloechidae Odening, 1964 (Family) by Virginia León-Règagnon, pages 460-469 Chapter 45: Lecithodendriidae Lühe, 1901 (Family) by Jeffrey M. Lotz, pages 470-479 Chapter 46: Opecoelidae Ozaki, 1925 (Family): The Richest Trematode Family by Storm B. Martin, pages 480-489 Digenea Summary Chapter 47: Summary of the Digenea (Subclass): Insights and Lessons from a Prominent Parasitologist by Robin M. Overstreet, pages 490-53

Expectations of and for Clerkship Directors 2.0: A Collaborative Statement from the Alliance for Clinical Education

This article presents an update of the collaborative statement on clerkship directors (CDs), first published in 2003, from the national undergraduate medical education organizations that comprise the Alliance for Clinical Education (ACE). The clerkship director remains an essential leader in the education of medical students on core clinical rotations, and the role of the CD has and continues to evolve. The selection of a CD should be an explicit contract between the CD, their department, and the medical school, with each party fulfilling their obligations to ensure the success of the students, the clerkship and of the CD. Educational innovations and accreditation requirements have evolved in the last two decades and therefore this article updates the 2003 standards for what is expected of a CD and provides guidelines for the resources and support to be provided. In their roles as CDs, medical student educators engage in several critical activities: administration, education/teaching, coaching, advising, and mentoring, faculty development, compliance with accreditation standards, and scholarly activity. This article describes (a) the work products that are the primary responsibility of the CD; (b) the qualifications for the CD; (c) the support structure, resources, and personnel that are necessary for the CD to accomplish their responsibilities; (d) incentives and career development for the CD; and (e) the dedicated time that should be provided for the clerkship and the CD to succeed. Given all that should rightfully be expected of a CD, a minimum of 50% of a full-time equivalent is recognized as appropriate. The complexity and needs of the clerkship now require that at least one full-time clerkship administrator (CA) be a part of the CD’s team. To better reflect the current circumstances, ACE has updated its recommendations for institutions and departments to have clear standards for what is expected of the director of a clinical clerkship and have correspondingly clear guidelines as to what should be expected for CDs in the support they are provided. This work has been endorsed by each of the eight ACE member organizations

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections

Virulent infectious agents such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and methicillin-resistant Staphylococcus aureus (MRSA) induce tissue damage that recruits neutrophils, monocyte, and macrophages, leading to T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils, monocytes, and macrophages recruited to pathogen-infected lungs, including SARS-CoV-2-infected lungs, express phosphatidylinositol 3-kinase gamma (PI3Kγ), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kγ deletion and inhibition with the clinical PI3Kγ inhibitor eganelisib promoted survival in models of infectious diseases, including SARS-CoV-2 and MRSA, by suppressing inflammation, vascular leak, organ damage, and cytokine storm. These results demonstrate essential roles for PI3Kγ in inflammatory lung disease and support the potential use of PI3Kγ inhibitors to suppress inflammation in severe infectious diseases