•High physical activity (PA) is associated with better muscle strength and power.•Low sedentary behavior (SB) is associated with better muscle strength and power.•PA/SB are stronger associated with ...lower body muscle strength and power than upper.•Strongest associations were found for PA/SB with chair stand test performance.•Confounding does not affect the association of PA/SB with muscle strength/power.
Engaging in physical activity (PA) and avoiding sedentary behavior (SB) are important for healthy ageing with benefits including the mitigation of disability and mortality. Whether benefits extend to key determinants of disability and mortality, namely muscle strength and muscle power, is unclear.
This systematic review aimed to describe the association of objective measures of PA and SB with measures of skeletal muscle strength and muscle power in community-dwelling older adults.
Six databases were searched from their inception to June 21st, 2020 for articles reporting associations between objectively measured PA and SB and upper body or lower body muscle strength or muscle power in community dwelling adults aged 60 years and older. An overview of associations was visualized by effect direction heat maps, standardized effect sizes were estimated with albatross plots and summarized in box plots. Articles reporting adjusted standardized regression coefficients (β) were included in meta-analyses.
A total of 112 articles were included representing 43,796 individuals (range: 21 to 3726 per article) with a mean or median age from 61.0 to 88.0 years (mean 56.4 % female). Higher PA measures and lower SB were associated with better upper body muscle strength (hand grip strength), upper body muscle power (arm curl), lower body muscle strength, and lower body muscle power (chair stand test). Median standardized effect sizes were consistently larger for measures of PA and SB with lower compared to upper body muscle strength and muscle power. The meta-analyses of adjusted β coefficients confirmed the associations between total PA (TPA), moderate-to-vigorous PA (MVPA) and light PA (LPA) with hand grip strength (β = 0.041, β = 0.057, and β = 0.070, respectively, all p ≤ 0.001), and TPA and MVPA with chair stand test (β = 0.199 and β = 0.211, respectively, all p ≤ 0.001).
Higher PA and lower SB are associated with greater skeletal muscle strength and muscle power, particularly with the chair stand test.
•Higher physical activity (PA) is associated with better global cognitive function.•Lower sedentary behavior (SB) is associated with better global cognitive function.•The greatest effect sizes were ...found for moderate-to-vigorous and total PA.
Both physical activity (PA) and sedentary behavior (SB) are important factors for healthy ageing. This systematic review aimed to determine the association of objectively assessed (instrumented) PA and SB with global cognitive function in older adults.
PubMed, Embase, the Cochrane Library (via Wiley), CINAHL, PsychINFO, and SPORTDiscus (via EBSCO) were searched from inception to June 21, 2020 for articles that described associations of objectively assessed PA/SB with global cognitive function in older adults aged 60 years and older. Results were synthesized using an effect direction heat map and albatross plots portrayed estimated effect sizes (standardized regression coefficients (βs)), which were summarized in boxplots.
In total, 45 articles were included representing a total of 15,817 older adults (mean/median age ranged from 65 to 88 years; 49.5% female). Longitudinal studies (n = 7) showed that higher moderate-to-vigorous and light PA (MVPA and LPA, respectively) and lower SB were associated with better global cognitive function. Standardized βs of cross-sectional studies (n = 38) showed that lower SB (median IQR, β = 0.078 0.004-0.184 and higher LPA (β = 0.096 0.046-0.188), activity counts (β = 0.131 0.049-0.224), number of steps (β = 0.155 0.096-0.246), MVPA (β = 0.163 0.069-0.285) and total PA (TPA) (β = 0.174 0.147-0.255) were associated with better global cognitive function.
Higher PA and lower SB are associated with better global cognitive function in older adults. The greatest estimated effect sizes were found for moderate-to-vigorous and TPA, suggesting that greater duration of any PA, and high intensity PA could be most beneficial for global cognitive function.
Activation of the Hippo pathway effector Yap underlies many liver cancers, however no germline or somatic mutations have been identified. Autophagy maintains essential metabolic functions of the ...liver, and autophagy-deficient murine models develop benign adenomas and hepatomegaly, which have been attributed to activation of the p62/Sqstm1-Nrf2 axis. Here, we show that Yap is an autophagy substrate and mediator of tissue remodeling and hepatocarcinogenesis independent of the p62/Sqstm1-Nrf2 axis. Hepatocyte-specific deletion of Atg7 promotes liver size, fibrosis, progenitor cell expansion, and hepatocarcinogenesis, which is rescued by concurrent deletion of Yap. Our results shed new light on mechanisms of Yap degradation and the sequence of events that follow disruption of autophagy, which is impaired in chronic liver disease.
Neutron scattering measurements on the pyrochlore magnet Ce2Zr2O7 reveal an unusual crystal field splitting of its lowest J=5/2 multiplet, such that its ground-state doublet is composed of mJ=±3/2, ...giving these doublets a dipole-octupole (DO) character with local Ising anisotropy. Its magnetic susceptibility shows weak antiferromagnetic correlations with θCW=−0.4(2) K, leading to a naive expectation of an all-in, all-out ordered state at low temperatures. Instead, our low-energy inelastic neutron scattering measurements show a dynamic quantum spin ice state, with suppressed scattering near |Q|=0, and no long-range order at low temperatures. This is consistent with recent theory predicting symmetry-enriched U(1) quantum spin liquids for such DO doublets decorating the pyrochlore lattice. Finally, we show that disorder, especially oxidation of powder samples, is important in Ce2Zr2O7 and could play an important role in the low-temperature behavior of this material.
Adenosine mediates immunosuppression within the tumor microenvironment through triggering adenosine 2A receptors (A2AR) on immune cells. To determine whether this pathway could be targeted as an ...immunotherapy, we performed a phase I clinical trial with a small-molecule A2AR antagonist. We find that this molecule can safely block adenosine signaling
. In a cohort of 68 patients with renal cell cancer (RCC), we also observe clinical responses alone and in combination with an anti-PD-L1 antibody, including subjects who had progressed on PD-1/PD-L1 inhibitors. Durable clinical benefit is associated with increased recruitment of CD8
T cells into the tumor. Treatment can also broaden the circulating T-cell repertoire. Clinical responses are associated with an adenosine-regulated gene-expression signature in pretreatment tumor biopsies. A2AR signaling, therefore, represents a targetable immune checkpoint distinct from PD-1/PD-L1 that restricts antitumor immunity. SIGNIFICANCE: This first-in-human study of an A2AR antagonist for cancer treatment establishes the safety and feasibility of targeting this pathway by demonstrating antitumor activity with single-agent and anti-PD-L1 combination therapy in patients with refractory RCC. Responding patients possess an adenosine-regulated gene-expression signature in pretreatment tumor biopsies.
.
.
We report a chemical substitution-induced ferromagnetic quantum critical point in polycrystalline Ni1−xRhx alloys. Through magnetization and muon spin relaxation measurements, we show that the ...ferromagnetic ordering temperature is suppressed continuously to zero at x crit = 0.375 while the magnetic volume fraction remains 100% up to x crit , pointing to a second order transition. Non-Fermi liquid behavior is observed close to x crit , where the electronic specific heat C el/T diverges logarithmically, while immediately above x crit the volume thermal expansion coefficient αV/T and the Grüneisen ratio Γ = αV/Cel both diverge logarithmically in the low temperature limit, further indication of a ferromagnetic quantum critical point in Ni1−xRhx.
Form‐fitting chemistry in a protein mold is enabled by the use of the 1,3‐dipolar cycloaddition of azides and alkynes. The enzyme acetylcholinesterase preferentially assembles one pair of these ...reactants, each of which bears a group that binds to adjacent positions on the protein structure (see picture), into a 1,2,3‐triazole adduct that is the most potent noncovalent inhibitor of the enzyme yet developed.
We present energy-resolved photoelectron momentum maps for orbital tomography that have been collected with a novel and efficient time-of-flight momentum microscopy setup. This setup is combined with ...a 0.5 MHz table-top femtosecond extreme-ultraviolet light source, which enables unprecedented speed in data collection and paves the way towards time-resolved orbital imaging experiments in the future. Moreover, we take a significant step forward in the data analysis procedure for orbital imaging, and present a sparsity-driven approach to the required phase retrieval problem, which uses only the number of non-zero pixels in the orbital. Here, no knowledge of the object support is required, and the sparsity number can easily be determined from the measured data. Used in the relaxed averaged alternating reflections algorithm, this sparsity constraint enables fast and reliable phase retrieval for our experimental as well as noise-free and noisy simulated photoelectron momentum map data.
PDF
