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51.
Brian Cox James Duffy Victor Zdorichenko Corentin Bellanger Jessica Hurcum Benoît Laleu Kevin I. Booker-Milburn Luke D. Elliott Michael Robertson-Ralph Christopher J. Swain Stephen J. Bishop Irene Hallyburton Mark Anderson 《ACS medicinal chemistry letters》2020,11(12):2497
We utilized synthetic photochemistry to generate novel sp3-rich scaffolds and report the design, synthesis, and biological testing of a diverse series of amides based on the 1-(amino-methyl)-2-benzyl-2-aza-bicyclo[2.1.1]hexane scaffold. Preliminary antimalarial screening of the library provided promising compounds with activity in the 1–5 μM range with an enhanced hit rate. Further evaluation (solubility, drug metabolism and pharmacokinetics (DMPK), and toxicity) of a selected compound (9) suggested that this series represents an excellent opportunity for further optimization with the framework offering multiple opportunities for the addition of uniquely vectorally positioned extra functionality. 相似文献
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Keane Lim Jason Smucny Deanna M Barch Max Lam Richard S E Keefe Jimmy Lee 《Schizophrenia bulletin》2021,47(3):712
Cognitive dysfunction is a core feature of schizophrenia. The subtyping of cognitive performance in schizophrenia may aid the refinement of disease heterogeneity. The literature on cognitive subtyping in schizophrenia, however, is limited by variable methodologies and neuropsychological tasks, lack of validation, and paucity of studies examining longitudinal stability of profiles. It is also unclear if cognitive profiles represent a single linear severity continuum or unique cognitive subtypes. Cognitive performance measured with the Brief Assessment of Cognition in Schizophrenia was analyzed in schizophrenia patients (n = 767). Healthy controls (n = 1012) were included as reference group. Latent profile analysis was performed in a schizophrenia discovery cohort (n = 659) and replicated in an independent cohort (n = 108). Longitudinal stability of cognitive profiles was evaluated with latent transition analysis in a 10-week follow-up cohort. Confirmatory factor analysis (CFA) was carried out to investigate if cognitive profiles represent a unidimensional structure. A 4-profile solution was obtained from the discovery cohort and replicated in an independent cohort. It comprised of a “less-impaired” cognitive subtype, 2 subtypes with “intermediate cognitive impairment” differentiated by executive function performance, and a “globally impaired” cognitive subtype. This solution showed relative stability across time. CFA revealed that cognitive profiles are better explained by distinct meaningful profiles than a severity linear continuum. Associations between profiles and negative symptoms were observed. The subtyping of schizophrenia patients based on cognitive performance and its associations with symptomatology may aid phenotype refinement, mapping of specific biological mechanisms, and tailored clinical treatments. 相似文献
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Vecchio Alyssa Nakigozi Gertrude Nakasujja Noeline Kisakye Alice Batte James Mayanja Richard Anok Aggrey Robertson Kevin Wawer Maria J. Sacktor Ned Rubin Leah H. Saylor Deanna 《Journal of neurovirology》2021,27(3):487-492
Journal of NeuroVirology - We investigated the prevalence and risk factors for frailty among people with HIV (PWH) in rural Uganda (n = 55, 47% male, mean age 44 years).... 相似文献
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Rumble Deanna D. O’Neal Katherine Overstreet Demario S. Penn Terence M. Jackson Pamela Aroke Edwin N. Sims Andrew M. King Annabel L. Hasan Fariha N. Quinn Tammie L. Long D. Leann Sorge Robert E. Goodin Burel R. 《Journal of behavioral medicine》2021,44(6):811-821
Journal of Behavioral Medicine - Individuals with chronic low back pain (cLBP) frequently report sleep disturbances. Living in a neighborhood characterized by low-socioeconomic status (SES) is... 相似文献
57.
Judith L. Swain Kenneth G. Morris Frederick P. Bruno Frederick R. Cobb 《The American journal of cardiology》1980,46(6):976-982
This study compared the noninvasive assessment of left ventricular function with radionuclide angiography with that obtained with ultrasonic sonomicrometry. Left ventricular ejection fraction and rate of ventricular ejection (dV/dt) were measured with both techniques over a wide range of ventricular function. Six dogs were prepared with epicardlal crystals across the major and minor axes of the left ventricle, paired transmural wall thickness crystals and a left ventricular catheter. The animals were studied while awake after they had recovered from operation. Left ventricular volume was calculated from the ultrasonic sonomicrometric dimension measurements and the equation for a prolate ellipsoid; dV/dt was calculated from the stroke volume and ejection time. Radionuclide angiograms were performed using technetium-99m-labeled red blood cells and an Anger camera with a converging collimator interfaced to a computer programmed for multigated acquisition.A wide range of ventricular function was produced with sequential infusion of isoproterenol, propranolol, phenylepnrine and sodium thiamylal. Ejection fraction and dV/dt were measured simultaneously during each intervention using the time-activity curves of the multigated radionuclide anglogram and ultrasonic sonomicrometric dimensions. Regression analyses demonstrated a close correlation between the simultaneous measurements of ejection fraction (r values ranged from 0.95 to 0.99) and dV/dt (r values ranged from 0.87 to 0.99). these data indicate that noninvasive multigated radionuclide angiography accurately assesses changes in ejection fraction and dV/dt over a wide range of ventricular function. 相似文献
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Raznahan A Greenstein D Lee NR Clasen LS Giedd JN 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(28):11366-11371
Prenatal life encompasses a critical phase of human brain development, but neurodevelopmental consequences of normative differences in prenatal growth among full-term pregnancies remain largely uncharted. Here, we combine the power of a within-monozygotic twin study design with longitudinal neuroimaging methods that parse dissociable components of structural brain development between ages 3 and 30 y, to show that subtle variations of the in utero environment, as indexed by mild birth weight (BW) variation within monozygotic pairs, are accompanied by statistically significant (i) differences in postnatal intelligence quotient (IQ) and (ii) alterations of brain anatomy that persist at least into late adolescence. Greater BW within the normal range confers a sustained and generalized increase in brain volume, which in the cortical sheet, is specifically driven by altered surface area rather than cortical thickness. Surface area is maximally sensitive to BW variation within cortical regions implicated in the biology of several mental disorders, the risk for which is modified by normative BW variation. We complement this near-experimental test of prenatal environmental influences on human brain development by replicating anatomical findings in dizygotic twins and unrelated singletons. Thus, using over 1,000 brain scans, across three independent samples, we link subtle differences in prenatal growth, within ranges seen among the majority of human pregnancies, to protracted surface area alterations, that preferentially impact later-maturing associative cortices important for higher cognition. By mapping the sensitivity of postnatal human brain development to prenatal influences, our findings underline the potency of in utero life in shaping postnatal outcomes of neuroscientific and public health importance. 相似文献
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