The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines.
View Article and Find Full Text PDFHematology Am Soc Hematol Educ Program
December 2024
Hyperpolarized (HP) C-labeled probes are emerging as promising agents to noninvasively image pH in vivo. HP [1,5-C]Z-OMPD (Z-4-methyl-2-oxopent-3-enedioic acid) in particular has recently been used to simultaneously report on kidney perfusion, filtration, and pH homeostasis, in addition to the ability to detect local tumor acidification. In previous studies, dissolution dynamic nuclear polarization was used to hyperpolarize Z-OMPD.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2024
It is normally supposed that populations of the same species should evolve shared mechanisms of adaptation to common stressors due to evolutionary constraint. Here, we describe a system of within-species local adaptation to coastal habitats, and detail surprising strategic variability in adaptive responses to high salinity. These different adaptive responses in neighboring populations are evidenced by transcriptomes, diverse physiological outputs, and distinct genomic selective landscapes.
View Article and Find Full Text PDFIntensive chemotherapy (IC) combination with second- or third-generation TKI improves survival compared to non-IC with first-generation TKI. Allo-HCT was suggestive of improving RFS/OS after propensity score matching and multivariable analysis.
View Article and Find Full Text PDFThe continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines.
View Article and Find Full Text PDFAcute myeloid leukemia (AML) is a fatal disease characterized by the accumulation of undifferentiated myeloblasts, and agents that promote differentiation have been effective in this disease but are not curative. Dihydroorotate dehydrogenase inhibitors (DHODHi) have the ability to promote AML differentiation and target aberrant malignant myelopoiesis. We introduce HOSU-53, a DHODHi with significant monotherapy activity, which is further enhanced when combined with other standard-of-care therapeutics.
View Article and Find Full Text PDFPurpose: Individuals diagnosed with cancer between 15 and 39 years (adolescent and young adult [AYA]) face unique vulnerability. Detail is lacking about care delivery for these patients, especially those with ALL. We address these knowledge gaps by describing AYA ALL care delivery details at National Cancer Institute Community Oncology Research Program (NCORP) (sub)affiliates by model of care.
View Article and Find Full Text PDFAnnu Int Conf IEEE Eng Med Biol Soc
July 2023
Developmental dysplasia of the hip (DDH) is a developmental deformity occurring in 0.1-3.4% of infants.
View Article and Find Full Text PDFHematology Am Soc Hematol Educ Program
December 2023
Background: Injuries are the leading cause of death and disability in preschool children who are subject to specific risk factors. We sought to clarify the determinants of unintentional injuries in children aged 5 years and under in high-income countries and report on the methodological quality of the selected studies.
Methods: A systematic review was conducted of observational studies investigating determinants of unintentional injury in children aged 0-5.
Type I interferons (IFN-I) are critical mediators of innate control of viral infections but also drive the recruitment of inflammatory cells to sites of infection, a key feature of severe coronavirus disease 2019. Here, IFN-I signaling was modulated in rhesus macaques (RMs) before and during acute SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection using a mutated IFN-α2 (IFN-modulator; IFNmod), which has previously been shown to reduce the binding and signaling of endogenous IFN-I. IFNmod treatment in uninfected RMs was observed to induce a modest up-regulation of only antiviral IFN-stimulated genes (ISGs); however, in SARS-CoV-2-infected RMs, IFNmod reduced both antiviral and inflammatory ISGs.
View Article and Find Full Text PDFExpert Opin Drug Metab Toxicol
November 2023
Introduction: Asparaginase is essential to chemotherapy regimens for acute lymphoblastic leukemia (ALL). Survival of patients with ALL has improved since incorporating asparaginase into chemotherapy backbones. Hispanic patients have a higher incidence of ALL than other ethnicities and suffer inferior outcomes.
View Article and Find Full Text PDFBlackshaw and Hendricks have recently developed and defended the impairment argument against abortion, arguing that the immorality of giving a child fetal alcohol syndrome (FAS) provides us with reason to believe that abortion is immoral. In this paper, we forward two criticisms of the impairment argument. First, we highlight that, as it currently stands, the argument is very weak and accomplishes very little.
View Article and Find Full Text PDFBackground: Dementia risk reduction is a public health priority and general practitioners (GPs) play a pivotal role in preventative healthcare. Therefore, risk assessment tools should be designed with GPs' preferences and perspectives in mind.
Objective: The LEAD! GP project aimed to investigate Australian GPs' preferences and perspectives relating to design, use and implementation of a new risk assessment tool that simultaneously calculates risk for four outcomes- dementia, diabetes mellitus, myocardial infarct, and stroke.
Background: People experiencing cognitive concerns and symptoms of depression or anxiety are at risk for Alzheimer's disease and dementia. We know physical activity can benefit cognition but understanding how to best support engagement is an ongoing challenge. Evidence-based conceptual models of factors underpinning physical activity engagement in target populations can inform intervention tailoring to address this challenge.
View Article and Find Full Text PDFC photosynthesis results from anatomical and biochemical characteristics that together concentrate CO around ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), increasing productivity in warm conditions. This complex trait evolved through the gradual accumulation of components, and particular species possess only some of these, resulting in weak C activity. The consequences of adding C components have been modelled and investigated through comparative approaches, but the intraspecific dynamics responsible for strengthening the C pathway remain largely unexplored.
View Article and Find Full Text PDFTo assess the use and acceptability of real-world evidence (RWE) in lung and hematologic cancer appraisals. A review of appraisals published by National Institute for Health and Care Excellence (NICE) in the UK was conducted. A total of 20 case studies employing RWE were identified and compared across five additional health technology assessment agencies: Scottish Medicines Consortium (SMC) (Scotland), CADTH (Canada), INESSS (Quebec), HAS (France) and IQWiG (Germany).
View Article and Find Full Text PDFBackground: While employment generally promotes positive health and wellbeing, some jobs may be less salutogenic than others. Few studies have examined mental health across a range of broadly defined occupation types using a large population sample.
Aims: To examine the prevalence of mental health problems across a wide range of occupation types, and further examine the association of family demands, controlling for key social determinants and health-related factors.