Successful Treatment of Refractory Post-Transplant Lymphoproliferative Disorder With Chimeric Antigen Receptor T-Cell Therapy in a Heart Transplant Recipient.

Post-transplant lymphoproliferative disorders (PTLDs) are opportunistic malignancies that complicate the success of hematopoietic stem cell or solid organ transplantation. These disorders often arise post-transplant due to the immunosuppression required for minimizing the risk of rejection of donor tissue. First-line treatment of these disorders includes limiting immunosuppression when permissible.

Sitravatinib combined with PD-1 blockade enhances cytotoxic T-cell infiltration by M2 to M1 tumor macrophage repolarization in esophageal adenocarcinoma.

Esophageal adenocarcinoma (EAC) is a leading cause of cancer-related mortality. Sitravatinib is a novel multi-gene tyrosine kinase inhibitor (TKI) that targets tumor-associated macrophage (TAM) receptors, VEGF, PDGF and c-Kit. Currently, sitravatinib is actively being studied in clinical trials across solid tumors and other TKIs have shown efficacy in combination with immune checkpoint inhibitors (ICI) in cancer models.

Cyclic Thrombocytopenia in the Setting of Intracranial Hemorrhage: A Diagnostic and Therapeutic Challenge.

Cyclic thrombocytopenia (CTP) as the name suggests presents with cyclic episodes of thrombocytopenia and is frequently initially misdiagnosed as immune thrombocytopenia. Following a lack of sustained response or abnormally increased response to common treatments used for immune thrombocytopenia, a proper diagnosis of CTP can then be made. Prior reports have shown a subset of patients who respond to cyclosporin A.

Branched montbretin A mimics allow derivatisation and potent amylase inhibition.

Mimics of the complex flavonol glycoside montbretin A in which a flavonol moiety is coupled to a caffeic acid partially peptidic linkers have proved to be potent inhibitors of human pancreatic alpha-amylase with potential as therapeutics for control of blood glucose levels. After exploring optimal linker length, a synthetic route to a version with a branched linker was devised based on the structure of the enzyme/inhibitor complex. The resultant branched inhibitors were shown to retain nanomolar potency even when decorated with polymers as a means of modifying solubility.

SARS-CoV-2 utilization of ACE2 from different bat species allows for virus entry and replication in vitro.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to have a zoonotic origin with bats suspected as a natural host. In this work, we individually express the ACE2 of seven bat species including, little brown, great roundleaf, Pearson's horseshoe, greater horseshoe, Brazilian free-tailed, Egyptian rousette, and Chinese rufous horseshoe in DF1 cells and determine their ability to support attachment and replication of SARS-CoV-2 viruses. We demonstrate that the ACE2 receptor of all seven species made DF1 cells permissible to SARS-CoV-2.

Identification of a second glycoform of the clinically prevalent O1 antigen from .

Carbapenemase and extended β-lactamase-producing isolates represent a major health threat, stimulating increasing interest in immunotherapeutic approaches for combating infections. Lipopolysaccharide O antigen polysaccharides offer viable targets for immunotherapeutic development, and several studies have described protection with O-specific antibodies in animal models of infection. O1 antigen is produced by almost half of clinical isolates.

Survival Benefit with Re-resection and Optimal Time to Re-resection in Gallbladder Cancer: a National Cancer Database Study.

Purpose: Gallbladder cancer is often diagnosed incidentally after cholecystectomy. Most patients will then undergo re-resection for potential residual disease; however, overall survival (OS) benefit data in this scenario is variable. This National Cancer Database analysis (NCDB) compared OS in patients with T1b-T3 gallbladder cancer who underwent re-resection and evaluated if time to resection impacts OS.

A Case of Vancomycin-Induced Severe Immune Thrombocytopenia.

A male in his 60s presented with left lower extremity fractures following a vehicle accident. Hemoglobin, initially, was 12.4 mmol/L, and platelet count was 235 k/mcl.

Vinyl Halide-Modified Unsaturated Cyclitols are Mechanism-Based Glycosidase Inhibitors.

Suitably configured allyl ethers of unsaturated cyclitols act as substrates of β-glycosidases, reacting via allylic cation transition states. Incorporation of halogens at the vinylic position of these carbasugars, along with an activated leaving group, generates potent inactivators of β-glycosidases. Enzymatic turnover of these halogenated cyclitols (F, Cl, Br) displayed a counter-intuitive trend wherein the most electronegative substituents yielded the most labile pseudo-glycosidic linkages.

Diffuse Large B Cell Lymphoma Raising Suspicion for an Infection: A Case Report.

Newly discovered liver lesions have a broad differential ranging from malignancy to infection. While tissue biopsy is the gold standard diagnostic modality, imaging can also aid in diagnosis. Hepatocellular carcinoma (HCC) can be diagnosed via imaging alone; however, masses suspicious for infection ultimately require biopsy and culture.

Development of an in vitro model for animal species susceptibility to SARS-CoV-2 replication based on expression of ACE2 and TMPRSS2 in avian cells.

The SARS-CoV-2 (SARS-CoV-2) virus has caused a worldwide pandemic because of the virus's ability to transmit efficiently human-to-human. A key determinant of infection is the attachment of the viral spike protein to the host receptor angiotensin-converting enzyme 2 (ACE2). Because of the presumed zoonotic origin of SARS-CoV-2, there is no practical way to assess the susceptibility of every species to SARS-CoV-2 by direct challenge studies.

Hypercellular bone marrow in aplastic anemia: A case report of two patients.

Aplastic anemia is a disorder of bone marrow failure characterized by a hypocellular bone marrow. We report two cases with an initial hypercellular bone marrow at the time of presentation, suggesting a new phase in the pathogenesis of the disease.

Development of an active site titration reagent for α-amylases.

α-Amylases are among the most widely used classes of enzymes in industry and considerable effort has gone into optimising their activities. Efforts to find better amylase mutants, such as through high-throughput screening, would be greatly aided by access to precise and robust active site titrating agents for quantitation of active mutants in crude cell lysates. While active site titration reagents designed for retaining β-glycosidases quantify these enzymes down to nanomolar levels, convenient titrants for α-glycosidases are not available.

A bifunctional O-antigen polymerase structure reveals a new glycosyltransferase family.

Lipopolysaccharide O-antigen is an attractive candidate for immunotherapeutic strategies targeting antibiotic-resistant Klebsiella pneumoniae. Several K. pneumoniae O-serotypes are based on a shared O2a-antigen backbone repeating unit: (→ 3)-α-Galp-(1 → 3)-β-Galf-(1 →).

New insights into lipopolysaccharide assembly and export.

Lipopolysaccharide is an important immunomodulatory and structural component found in the outer membrane of Gram-negative bacteria. The biosynthesis of this glycoconjugate proceeds by a highly conserved pathway and, as such, is an attractive target for antibiotic action. We highlight here recent work focused on understanding this pathway with an emphasis on new insights related to chain length control and transport across the inner and outer cell membranes.

O1 and O2ac antigens provide prototypes for an unusual strategy for polysaccharide antigen diversification.

A limited range of different structures is observed in O-antigenic polysaccharides (OPSs) from lipopolysaccharides. Among these, several are based on modifications of a conserved core element of serotype O2a OPS, which has a disaccharide repeat structure [→3)-α-d-Gal-(1→3)-β-d-Gal-(1→]. Here, we describe the enzymatic pathways for a highly unusual modification strategy involving the attachment of a second glycan repeat-unit structure to the nonreducing terminus of O2a.

A Route to Polyprenol Pyrophosphate-Based Probes of O-Polysaccharide Biosynthesis in Klebsiella pneumoniae O2a.

An approach for the assembly of polyprenol pyrophosphate-based probes of O-polysaccharide biosynthesis in Klebsiella pneumoniae serotype O2a is described. This convergent route features high-yielding, diastereoselective glycosylations and the late-stage installation of the polyprenol pyrophosphate moiety. Although applied to the synthesis of a nonasaccharide bearing a farnesyl group (1), the modular nature of the route makes it amenable to the synthesis of additional derivatives containing either larger glycans or different lipid domains.

The LPG1x family from Leishmania major is constituted of rare eukaryotic galactofuranosyltransferases with unprecedented catalytic properties.

Galactofuranosyltransferases are poorly described enzymes despite their crucial role in the virulence and the pathogenicity of numerous microorganisms. These enzymes are considered as potential targets for therapeutic action. In addition to the only well-characterised prokaryotic GlfT2 from Mycobacterium tuberculosis, four putative genes in Leishmania major were previously described as potential galactofuranosyltransferases.

Rearranged T Cell Receptor Sequences in the Germline Genome of Channel Catfish Are Preferentially Expressed in Response to Infection.

Rearranged V(D)J genes coding for T cell receptor α and β chains are integrated into the germline genome of channel catfish. Previous analysis of expressed TCR Vβ2 repertoires demonstrated that channel catfish express multiple public clonotypes, which were shared among all the fish, following infection with a common protozoan parasite. In each case a single DNA sequence was predominately used to code for a public clonotype.

Synthesis of the Campylobacter jejuni 81-176 Strain Capsular Polysaccharide Repeating Unit Reveals the Absolute Configuration of its O-Methyl Phosphoramidate Motif.

The O-methyl phosphoramidate (MeOPN) motif is a non-stoichiometric modification of capsular polysaccharides (CPS) in ≈70 % of all Campylobacter jejuni strains. Infections by C. jejuni lead to food-borne illnesses and the CPS they produce are key virulence factors.

Stereocontrolled Synthesis of 2-Deoxy-galactopyranosides via Isopropylidene-Protected 6- O-Silylated Donors.

The stereocontrolled synthesis of 2-deoxy-d- arabino-hexopyranosides ("galactopyranosides") using 3,4- O-isopropylidene-6- O- tert-butyldiphenylsilyl-protected glycosyl donors is reported. 2-Deoxy-thioglycoside 3e gives excellent α-selectivity, while galactal 9 leads to, in a two-step protocol, 2-deoxy-β-glycosides in high stereoselectivity. The selectivity of both reagents is believed to arise from the combination of the isopropylidene acetal spanning O-3 and O-4 together with the sterically demanding silyl group on O-6.

Hand-held Dynamometer Positioning Impacts Discomfort During Quadriceps Strength Testing: A Validity and Reliability Study.

Purpose/background: A belt-stabilized hand-held dynamometer (HHD) offers the ability to quantify quadriceps muscle strength in a clinical environment, but a limitation is participant discomfort at the interface between the HHD and the tibia. The purpose of this study was to quantify the level of discomfort associated with a modified belt-stabilized HHD configuration compared to a standard belt-stabilized configuration and an isokinetic dynamometer. The secondary purpose of this study was to determine the validity and reliability of a modified configuration used to measure quadriceps strength compared to the "gold-standard" isokinetic dynamometer.