Including cover crops within agricultural rotations may increase soil organic carbon (SOC). However, contradictory findings generated by on-site experiments make it necessary to perform a ...comprehensive assessment of interactions between cover crops, environmental and management factors, and changes in SOC. In this study, we collected data from studies that compared agricultural production with and without cover crops, and then analyzed those data using meta-analysis and regression. Our results showed that including cover crops into rotations significantly increased SOC, with an overall mean change of 15.5% (95% confidence interval of 13.8%–17.3%). Whereas medium-textured soils had highest SOC stocks (overall means of 39 Mg ha−1 with and 37 Mg ha−1 without cover crops), fine-textured soils showed the greatest increase in SOC after the inclusion of cover crops (mean change of 39.5%). Coarse-textured (11.4%) and medium-textured soils (10.3%) had comparatively smaller changes in SOC, while soils in temperate climates had greater changes (18.7%) than those in tropical climates (7.2%). Cover crop mixtures resulted in greater increases in SOC compared to mono-species cover crops, and using legumes caused greater SOC increases than grass species. Cover crop biomass positively affected SOC changes while carbon:nitrogen ratio of cover crop biomass was negatively correlated with SOC changes. Cover cropping was associated with significant SOC increases in shallow soils (≤30 cm), but not in subsurface soils (>30 cm). The regression analysis revealed that SOC changes from cover cropping correlated with improvements in soil quality, specifically decreased runoff and erosion and increased mineralizable carbon, mineralizable nitrogen, and soil nitrogen. Soil carbon change was also affected by annual temperature, number of years after start of cover crop usage, latitude, and initial SOC concentrations. Finally, the mean rate of carbon sequestration from cover cropping across all studies was 0.56 Mg ha−1 yr−1. If 15% of current global cropland were to adopt cover crops, this value would translate to 0.16 ± 0.06 Pg of carbon sequestered per year, which is ~1–2% of current fossil fuels emissions. Altogether, these results indicated that the inclusion of cover crops into agricultural rotations can enhance soil carbon concentrations, improve many soil quality parameters, and serve as a potential sink for atmosphere CO2.
•Cover cropping increases SOC in near-surface soils by an average of 15.5%.•SOC changes were correlated with decreased erosion and increased mineralizable carbon.•SOC change was affected by annual temperature, latitude, and initial SOC concentrations.•Fine-textured soils showed greatest rates of SOC increase after cover cropping.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
High labor demand for physician assistants/associates (PA) has led to substantial PA workforce and wage growth. During this growth period, states have adopted reforms to reduce PA scope of practice ...restrictions and reports of significant gender and race wage disparities have emerged. This study examined data from the American Community Survey to investigate the influence of demographic characteristics, human capital, and scope of practice reforms on PA wages from 2008 to 2017. Using an ordinary least squares two-way fixed effects estimator, a significant association between reforms and PA wages could not be established. Rather, wages were found to be strongly associated with human capital and demographic characteristics. Gender and race wage disparities persist, with female PAs earning 7.5% lower wages than male PAs and White PAs earning 9.1% to 14.5% higher wages than racial and ethnic minority PAs. These findings suggest a minimal influence of prior scope of practice reforms on PA wages.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
While thousands of long noncoding RNAs (lncRNAs) have been identified, few lncRNAs that control neural stem cell (NSC) behavior are known. Here, we identify Pinky (Pnky) as a neural-specific lncRNA ...that regulates neurogenesis from NSCs in the embryonic and postnatal brain. In postnatal NSCs, Pnky knockdown potentiates neuronal lineage commitment and expands the transit-amplifying cell population, increasing neuron production several-fold. Pnky is evolutionarily conserved and expressed in NSCs of the developing human brain. In the embryonic mouse cortex, Pnky knockdown increases neuronal differentiation and depletes the NSC population. Pnky interacts with the splicing regulator PTBP1, and PTBP1 knockdown also enhances neurogenesis. In NSCs, Pnky and PTBP1 regulate the expression and alternative splicing of a core set of transcripts that relates to the cellular phenotype. These data thus unveil Pnky as a conserved lncRNA that interacts with a key RNA processing factor and regulates neurogenesis from embryonic and postnatal NSC populations.
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•The lncRNA Pnky is expressed in mouse and human neural stem cells in vivo•Pnky knockdown increases neuronal differentiation in culture and in vivo•Pnky localizes to the nucleus and interacts with the mRNA splicing regulator PTBP1•PTBP1 and Pnky regulate expression of key transcripts related to differentiation
Ramos et al. describe Pinky (Pnky), a neural-specific lncRNA that localizes to the nucleus of neural stem cells (NSCs). Pnky knockdown in NSCs increases neurogenesis. Pnky interacts with splicing regulator PTBP1, and PTBP1 and Pnky regulate the expression and splicing of a core set of transcripts related to neuronal differentiation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background. The efficacy of tenofovir disoproxil fumarate (TDF) as part of combination antiretroviral treatment (ART) has been demonstrated in several randomized, controlled trials. However, an ...increasing number of case reports suggest that TDF use may be associated with significant nephrotoxicity. Our objective was to determine the renal safety of TDF-containing ART regimens for HIV-infected individuals. Methods. MEDLINE, EMBASE, Global Health, Scopus, Biosis Previews, Cochrane Library, Web of Science, and existing systematic reviews were searched. Prospective studies comparing TDF-containing with non-TDF containing ART regimens were selected for inclusion. We extracted data on study characteristics, participant characteristics, therapeutic interventions, renal function, bone density, and fracture rates. Results. A total of 17 studies (including 9 randomized, controlled trials) met the selection criteria. Median sample size was 517 participants. Constituent ART regimens were diverse. There was a significantly greater loss of kidney function among the TDF recipients, compared with control subjects (mean difference in calculated creatinine clearance, 3.92 mL/min; 95% confidence interval CI, 2.13–5.70 mL/min), as well as a greater risk of acute renal failure (risk difference, 0.7%; 95% CI, 0.2–1.2). There was no evidence that TDF use led to increased risk of severe proteinuria, hypophosphatemia, or fractures. Conclusions. Although TDF use was associated with a statistically significant loss of renal function, the clinical magnitude of this effect was modest. Our findings do not support the need to restrict TDF use in jurisdictions where regular monitoring of renal function and serum phosphate levels is impractical.
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BFBNIB, NUK, PNG, UL, UM, UPUK
Synthetic polymer membranes, critical to diverse energy-efficient separations, are subject to permeability-selectivity trade-offs that decrease their overall efficacy. These trade-offs are due to ...structural variations (e.g., broad pore size distributions) in both nonporous membranes used for Angstrom-scale separations and porous membranes used for nano to micron-scale separations. Biological membranes utilize well-defined Angstrom-scale pores to provide exceptional transport properties and can be used as inspiration to overcome this trade-off. Here, we present a comprehensive demonstration of such a bioinspired approach based on pillar5arene artificial water channels, resulting in artificial water channel-based block copolymer membranes. These membranes have a sharp selectivity profile with a molecular weight cutoff of ~ 500 Da, a size range challenging to achieve with current membranes, while achieving a large improvement in permeability (~65 L m
h
bar
compared with 4-7 L m
h
bar
) over similarly rated commercial membranes.
ABSTRACTFragala, MS, Cadore, EL, Dorgo, S, Izquierdo, M, Kraemer, WJ, Peterson, MD, and Ryan, ED. Resistance training for older adultsposition statement from the national strength and conditioning ...association. J Strength Cond Res XX(X)000–000, 2019—Aging, even in the absence of chronic disease, is associated with a variety of biological changes that can contribute to decreases in skeletal muscle mass, strength, and function. Such losses decrease physiologic resilience and increase vulnerability to catastrophic events. As such, strategies for both prevention and treatment are necessary for the health and well-being of older adults. The purpose of this Position Statement is to provide an overview of the current and relevant literature and provide evidence-based recommendations for resistance training for older adults. As presented in this Position Statement, current research has demonstrated that countering muscle disuse through resistance training is a powerful intervention to combat the loss of muscle strength and muscle mass, physiological vulnerability, and their debilitating consequences on physical functioning, mobility, independence, chronic disease management, psychological well-being, quality of life, and healthy life expectancy. This Position Statement provides evidence to support recommendations for successful resistance training in older adults related to 4 parts(a) program design variables, (b) physiological adaptations, (c) functional benefits, and (d) considerations for frailty, sarcopenia, and other chronic conditions. The goal of this Position Statement is to a) help foster a more unified and holistic approach to resistance training for older adults, b) promote the health and functional benefits of resistance training for older adults, and c) prevent or minimize fears and other barriers to implementation of resistance training programs for older adults.
The respiratory immune response consists of multiple tiers of cellular responses that are engaged in a sequential manner in order to control infections. The stepwise engagement of effector functions ...with progressively increasing host fitness costs limits tissue damage. In addition, specific mechanisms are in place to promote disease tolerance in response to respiratory infections. Environmental factors, obesity and the ageing process can alter the efficiency and regulation of this tiered response, increasing pathology and mortality as a result. In this Review, we describe the cell types that coordinate pathogen clearance and tissue repair through the serial secretion of cytokines, and discuss how the environment and comorbidity influence this response.
Summary Background Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer (NSCLC) setting. ...The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy. We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC. Methods In this randomised, open-label, phase 2 cohort of a multicohort study (KEYNOTE-021), patients were enrolled at 26 medical centres in the USA and Taiwan. Patients with chemotherapy-naive, stage IIIB or IV, non-squamous NSCLC without targetable EGFR or ALK genetic aberrations were randomly assigned (1:1) in blocks of four stratified by PD-L1 tumour proportion score (<1% vs ≥1%) using an interactive voice-response system to 4 cycles of pembrolizumab 200 mg plus carboplatin area under curve 5 mg/mL per min and pemetrexed 500 mg/m2 every 3 weeks followed by pembrolizumab for 24 months and indefinite pemetrexed maintenance therapy or to 4 cycles of carboplatin and pemetrexed alone followed by indefinite pemetrexed maintenance therapy. The primary endpoint was the proportion of patients who achieved an objective response, defined as the percentage of patients with radiologically confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by masked, independent central review, in the intention-to-treat population, defined as all patients who were allocated to study treatment. Significance threshold was p<0·025 (one sided). Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned study treatment. This trial, which is closed for enrolment but continuing for follow-up, is registered with ClinicalTrials.gov , number NCT02039674. Findings Between Nov 25, 2014, and Jan 25, 2016, 123 patients were enrolled; 60 were randomly assigned to the pembrolizumab plus chemotherapy group and 63 to the chemotherapy alone group. 33 (55%; 95% CI 42–68) of 60 patients in the pembrolizumab plus chemotherapy group achieved an objective response compared with 18 (29%; 18–41) of 63 patients in the chemotherapy alone group (estimated treatment difference 26% 95% CI 9–42%; p=0·0016). The incidence of grade 3 or worse treatment-related adverse events was similar between groups (23 39% of 59 patients in the pembrolizumab plus chemotherapy group and 16 26% of 62 in the chemotherapy alone group). The most common grade 3 or worse treatment-related adverse events in the pembrolizumab plus chemotherapy group were anaemia (seven 12% of 59) and decreased neutrophil count (three 5%); an additional six events each occurred in two (3%) for acute kidney injury, decreased lymphocyte count, fatigue, neutropenia, and sepsis, and thrombocytopenia. In the chemotherapy alone group, the most common grade 3 or worse events were anaemia (nine 15% of 62) and decreased neutrophil count, pancytopenia, and thrombocytopenia (two 3% each). One (2%) of 59 patients in the pembrolizumab plus chemotherapy group experienced treatment-related death because of sepsis compared with two (3%) of 62 patients in the chemotherapy group: one because of sepsis and one because of pancytopenia. Interpretation Combination of pembrolizumab, carboplatin, and pemetrexed could be an effective and tolerable first-line treatment option for patients with advanced non-squamous NSCLC. This finding is being further explored in an ongoing international, randomised, double-blind, phase 3 study. Funding Merck & Co.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Fluorination is commonly employed to optimize bioactivity and pharmaco-kinetic properties of drug candidates. Aliphatic fluorination often reduces the lipophilicity (log P), but polyfluoroalkylation ...typically increases lipophilicity. Hence, identification of polyfluorinated motifs that nonetheless lead to similar or even reduced lipophilicities is of interest to expand the arsenal of medicinal chemistry tools in tackling properties such as compound metabolic stability or off-target selectivity. We show that changing a CF3-group of a perfluoroalkyl chain to a methyl group leads to a drastic reduction in lipophilicity. We also show that changing a C–F bond of a trifluoromethyl group, including when incorporated as part of a perfluoroalkyl group, to a C–Me group, leads to a reduction in log P, despite the resulting chain elongation. The observed lipophilicity trends were identified in fluorinated alkanol models and reproduced when incorporated in analogues of a drug candidate, and the metabolic stability of these motifs was demonstrated.
Microbiota alterations are linked with colorectal cancer (CRC) and notably higher abundance of putative oral bacteria on colonic tumours. However, it is not known if colonic mucosa-associated taxa ...are indeed orally derived, if such cases are a distinct subset of patients or if the oral microbiome is generally suitable for screening for CRC.
We profiled the microbiota in oral swabs, colonic mucosae and stool from individuals with CRC (99 subjects), colorectal polyps (32) or controls (103).
Several oral taxa were differentially abundant in CRC compared with controls, for example,
and
s pp. A classification model of oral swab microbiota distinguished individuals with CRC or polyps from controls (sensitivity: 53% (CRC)/67% (polyps); specificity: 96%). Combining the data from faecal microbiota and oral swab microbiota increased the sensitivity of this model to 76% (CRC)/88% (polyps). We detected similar bacterial networks in colonic microbiota and oral microbiota datasets comprising putative oral biofilm forming bacteria. While these taxa were more abundant in CRC, core networks between pathogenic, CRC-associated oral bacteria such as
,
and
were also detected in healthy controls. High abundance of Lachnospiraceae was negatively associated with the colonisation of colonic tissue with oral-like bacterial networks suggesting a protective role for certain microbiota types against CRC, possibly by conferring colonisation resistance to CRC-associated oral taxa and possibly mediated through habitual diet.
The heterogeneity of CRC may relate to microbiota types that either predispose or provide resistance to the disease, and profiling the oral microbiome may offer an alternative screen for detecting CRC.
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