Safe and Orally Bioavailable Inhibitor of Serine Palmitoyltransferase Improves Age-Related Sarcopenia.

The accumulation of ceramides and related metabolites has emerged as a pivotal mechanism contributing to the onset of age-related diseases. However, small molecule inhibitors targeting the ceramide synthesis pathway for clinical use are currently unavailable. We synthesized a safe and orally bioavailable inhibitor, termed ALT-007, targeting the rate-limiting enzyme of ceramide synthesis, serine palmitoyltransferase (SPT).

CD57 EMRA CD8 T cells in cancer patients over 70: associations with prior chemotherapy and response to anti-PD-1/PD-L1 therapy.

Background: Immune ageing complicates cancer treatment in older individuals. While immunotherapy targeting the PD-1/PD-L1 pathway can reinvigorate T cells, these cells tend to become senescent with age. This study investigates different CD8 T cell subsets usually associated with senescence, in cancer patients over 70 years old who are undergoing anti-PD-1/PD-L1 immunotherapy, and examines the relationship between these senescent cells and prior chemotherapy exposure.

Structure-based discovery of first inhibitors targeting the helicase activity of human PIF1.

PIF1 is a conserved helicase and G4 DNA binding and unwinding enzyme, with roles in genome stability. Human PIF1 (hPIF1) is poorly understood, but its functions can become critical for tumour cell survival during oncogene-driven replication stress. Here we report the discovery, via an X-ray crystallographic fragment screen (XChem), of hPIF1 DNA binding and unwinding inhibitors.

Atomic-Level Structure of the Organic-Inorganic Interface of Colloidal ZnO Nanoplatelets from Dynamic Nuclear Polarization-Enhanced NMR.

Colloidal semiconductor nanoplatelets (NPLs) have emerged as a new class of nanomaterials that can exhibit substantially distinct optical properties compared to those of isotropic quantum dots, which makes them prime candidates for new-generation optoelectronic devices. Insights into the structure and anisotropic growth of NPLs can offer a blueprint for their controlled fabrication. Here, we present an atomic-level investigation of the organic-inorganic interface structure in ultrathin and stable benzamidine ()-supported ZnO NPLs prepared by the modified ne-pot elf-upporting rganoetallic approach.

Dehydration regulates structural reorganization of dynamic hydrogels.

The dehydration process is widely recognized as a significant phenomenon in nature. Hydrogels, which are important functional materials with high water content and crosslinked networks, encounter the issue of dehydration in their practical applications. Here, we report the distinctive anisotropic dehydration modality of dynamic hydrogels, which is fundamentally different from the more commonly observed isotropic dehydration of covalent hydrogels.

Portal vein thrombosis: diagnosis, management, and endpoints for future clinical studies.

Portal vein thrombosis (PVT) refers to the development of a non-malignant obstruction of the portal vein, its branches, its radicles, or a combination. This Review first provides a comprehensive overview of all aspects of PVT, namely the specifics of the portal venous system, the risk factors for PVT, the pathophysiology of portal hypertension in PVT, the interest in non-invasive tests, as well as therapeutic approaches including the effect of treating risk factors for PVT or cause of cirrhosis, anticoagulation, portal vein recanalisation by interventional radiology, and prevention and management of variceal bleeding in patients with PVT. Specific issues are also addressed including portal cholangiopathy, mesenteric ischaemia and intestinal necrosis, quality of life, fertility, contraception and pregnancy, and PVT in children.

Prognostic impact of neurocognitive disorders in older patients with cancer: the ELCAPA prospective cohort study.

Objective: To assess the prognostic value of neurocognitive disorder (NCD) for 12 month-overall mortality in patients aged 70 or more with a solid cancer.

Design: prospective, observational, multicenter cohort.

Setting And Participants: We analyzed data from the ELCAPA longitudinal multicenter observational cohort of patients aged 70 or over, referred for a geriatric assessment (GA) before a new cancer treatment modality between January 31st, 2007, and December 29th, 2017.

Acute pulmonary injury in hematology patients supported with pathogen-reduced and conventional platelet components.

Patients treated with antineoplastic therapy often develop thrombocytopenia requiring platelet transfusion, which has potential to exacerbate pulmonary injury. This study tested the hypothesis that amotosalen-UVA pathogen-reduced platelet components (PRPCs) do not potentiate pulmonary dysfunction compared with conventional platelet components (CPCs). A prospective, multicenter, open-label, sequential cohort study evaluated the incidence of treatment-emergent assisted mechanical ventilation initiated for pulmonary dysfunction (TEAMV-PD).

Semiconducting Polymer Dots Directly Stabilized with Serum Albumin: Preparation, Characterization, and Cellular Immunolabeling.

Semiconducting polymer dots (Pdots) are brightly fluorescent nanoparticles of growing interest for bioanalysis and imaging. A recurring challenge with these materials is obtaining robust physical and colloidal stability and low nonspecific binding. Here, we prepared and characterized Pdots with bovine serum albumin (BSA) as the stabilizing agent (BSA-Pdots) instead of a more conventionally used amphiphilic polymer, both without and with cross-linking of the protein using glutaraldehyde (BSA(GA)-Pdots) or disuccinimidyl glutarate.

Increased red blood cell alloimmunization rates in transfused aplastic anemia and myelofibrosis patients.

Background: Red blood cell (RBC) alloimmunization (AI) is a well-known complication of RBC transfusions, which results in the formation of alloantibodies to non-self antigens on donor RBCs, putting patients at risk of transfusion-related complications. The rate of AI with RBC transfusions in the general hospitalized population is estimated to be 2%-3%. However, some patients who are deemed "transfusion-dependent" require regular transfusions of blood products due to persistently low cell counts, putting them at even greater risk of RBC AI and increased morbidity.

Development of New Donor-Specific and Human Leukocyte Antigen Antibodies After Transfusion in Adult Lung Transplantation.

Objectives: The development of new human leukocyte antigens (HLAs) and donor-specific antibodies (DSAs) in patients are associated with worse outcomes following lung transplantation. The authors aimed to examine the relationship between blood product transfusion in the first 72 hours after lung transplantation and the development of HLA antibodies, including DSAs.

Design: A retrospective observational study.

Massive Transfusion Protocol Adherence: Relationship to Trauma Patient Outcomes.

Background: Ongoing evaluation of massive transfusion protocol adherence is critical to ensure better trauma patient outcomes.

Objective: This quality improvement initiative aimed to determine provider adherence to a recently revised massive transfusion protocol and its relationship to clinical outcomes among trauma patients requiring massive transfusion.

Methods: A retrospective, descriptive, correlational design was used to determine the association between provider adherence to a recently revised massive transfusion protocol and clinical outcomes in trauma patients with hemorrhage treated at a Level I trauma center from November 2018 to October 2020.

External Validity of Two Scores for Predicting the Risk of Chemotherapy Toxicity Among Older Patients With Solid Tumors: Results From the ELCAPA Prospective Cohort.

Background: Severe chemotherapy-related toxicities are frequent among older patients. The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) and the Cancer and Aging Research Group Study (CARG) score were both developed to predict these events.

Patients And Methods: The objective of this study was to evaluate the scores' predictive performance in a prospective cohort, which included patients aged 70 years and older referred for a geriatric assessment prior to chemotherapy for a solid tumor.

Safety and efficacy of immunotherapy according to the age threshold of 80 years.

Background: To compare safety and efficacy of ICIs among patients<80 and those ≥80 years of age.

Methods: A single-center retrospective observational cohort study comparing patients<80 and ≥80 years of age matched for cancer site (lung vs others) and participation in a clinical trial.

Primary Endpoint: grade ≥2 toxicity during the first three months of ICI therapy.