bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA release via membrane vesicles in Pseudomonas aeruginosa PAO1 is associated with the growth phase
Authors: Pérez‐Cruz Carla , Briansó Ferran , Sonnleitner Elisabeth , Bläsi Udo , Mercadé Elena 
Published: March 2021

SummaryPseudomonas aeruginosa PAO1 membrane vesicles (MVs) are known to play a role in cell‐to‐cell communication. Several studies have shown that the MV composition and physicochemical properties vary according to the bacterial growth stage, but the impact this might have on the externalization of RNA via MVs has not been addressed. Therefore, a study to characterize the RNA content from MVs retrieved at different growth phases was conducted. First, the transcriptome analyses revealed a higher abundance of around 300 RNA species in MVs when compared with the cells. The vesiculation rate along the growth curve was determined, showing that the release of MVs increased during the transition to the stationary phase, whereas it decreased in the late stationary phase. RNA‐seq of MVs retrieved along the transition to the stationary phase demonstrated that the RNA cargo of vesicles did not vary. However, the amount of smaller RNAs (<200 nt) inside MVs retrieved in the late exponential phase was higher than in the stationary phase MVs. These results indicate that the externalization of RNA via MVs occurs during late exponential phase and implies the secretion of different types of MVs during growth.
Survival finance and the politics of equal pay
Authors: Sobering Katherine 
Published: March 2021

AbstractWage gaps constitute a major component of workplace inequality. While scholars have explored the causes and consequences of differences in pay, very few question the basic presumption that workers are paid differently in the first place. Drawing on ethnographic research in a worker cooperative with a policy of equal pay, this article analyses how the organization compensated its members in the context of low wages, economic uncertainty, and insufficient social benefits. Over time, I found that members justified small variations that led to wage difference without amending their commitment to pay equity. This was made possible through a system of survival finance, a set of compensation practices that supports the reproduction of both individual members and the organization as a whole. Whereas members understood money wages as market‐based incentives for labor, the cooperative enacted its principles of equality and fairness by compensating members with alternative currencies (time) and additional benefits (zero interest rate credit) to help make ends meet. The article concludes by reflecting on the challenges of equalizing pay and its implications for reducing workplace inequality.
Regulating digital therapeutics for mental health: Opportunities, challenges, and the essential role of psychologists
Authors: Carl Jenna R. , Jones Deborah J. , Lindhiem Oliver J. , Doss Brian D. , Weingardt Kenneth R. , Timmons Adela C. , Comer Jonathan S. 
Published: March 2021

With so many promising digital therapeutics for anxiety and obsessive‐compulsive (OC) spectrum problems, there is an urgent need to consider how evolving regulatory oversight of digital therapeutics is poised to shift how these tools are developed, evaluated, reimbursed, and delivered. In this commentary, we discuss both opportunities and potential pitfalls associated with emerging government regulations of digital therapeutics for mental health, and we consider how applying the traditional ‘prescription‐based’ medical approval paradigm to digital therapeutics for mental health could ultimately undermine and limit the broad accessibility of these software‐based innovations that have been explicitly designed to expand the accessibility of care. For example, the vast majority of behavioural and mental health providers do not have ‘prescription privileges’ (a term originally rooted in pharmacologic practices), and as a result, under current regulations in the U.S. would not be authorized to make FDA‐cleared digital therapeutics available to their patients. This is particularly concerning given that most digital therapeutics for mental health are directly rooted in psychological and behavioural science, yet psychologists would not be authorized to incorporate these innovations into their practice. We consider how synchronizing regulatory standards across countries may prove useful, and we conclude by arguing that multidisciplinary teams making regulatory decisions concerning digital therapeutics for mental health must include representation from the discipline and practice of psychology.Practitioner points

Emerging government regulations of digital therapeutics for mental health present both opportunities and potential pitfalls

Applying the traditional ‘prescription‐based’ medical approval paradigm to digital therapeutics for mental health could ultimately undermine the broad accessibility of these software‐based innovations.

Synchronizing regulatory standards across countries may prove useful.

Multidisciplinary teams making regulatory decisions concerning digital therapeutics for mental health must include representation from the field of psychology.
Activation of soluble guanylyl cyclase signalling with cinaciguat improves impaired kidney function in diabetic mice
Authors: Harloff Manuela , Prüschenk Sally , Seifert Roland , Schlossmann Jens 
Published: March 2021

Background and PurposeDiabetic nephropathy is the leading cause for end‐stage renal disease worldwide. Until now, there is no specific therapy available. Standard treatment with inhibitors of the renin‐angiotensin system just slows down progression. However, targeting the NO/sGC/cGMP pathway using sGC activators does prevent kidney damage. Thus, we investigated if the sGC activator cinaciguat was beneficial in a mouse model of diabetic nephropathy, and we analysed how mesangial cells (MCs) were affected by related conditions in cell culture.Experimental ApproachType 1 diabetes was induced with streptozotocin in wild‐type and endothelial NOS knockout (eNOS KO) mice for 8 or 12 weeks.. Half of these mice received cinaciguat in their chow for the last 4 weeks. Kidneys from the diabetic mice were analysed with histochemical assays and by RT‐PCR and western blotting. . Additionally, primary murine MCs under diabetic conditions were stimulated with 8‐Br‐cGMP or cinaciguat to activate the sGC/cGMP pathway.Key ResultsThe diabetic eNOS KO mice developed most characteristics of diabetic nephropathy, most marked at 12 weeks. Treatment with cinaciguat markedly improved GFR, serum creatinine, mesangial expansion and kidney fibrosis in these animals. We determined expression levels of related signalling proteins. Thrombospondin 1, a key mediator in kidney diseases, was strongly up‐regulated under diabetic conditions and this increase was suppressed by activation of sGC/cGMP signalling.Conclusion and ImplicationsActivation of the NO/sGC/PKG pathway with cinaciguat was beneficial in a model of diabetic nephropathy. Activators of sGC might be an appropriate therapy option in patients with Type 1 diabetes.LINKED ARTICLESThis article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc
Changes in local brain function in mild cognitive impairment due to semantic dementia
Authors: Cui Liang , Chen Keliang , Huang Lin , Sun Jiawei , Lv Yating , Jia Xize , Guo Qihao 
Published: March 2021

AbstractAimsMild cognitive impairment due to semantic dementia represents the preclinical stage, involving cognitive decline dominated by semantic impairment below the semantic dementia standard. Therefore, studying mild cognitive impairment due to semantic dementia may identify changes in patients before progression to dementia. However, whether changes in local functional activity occur in preclinical stages of semantic dementia remains unknown. Here, we explored local functional changes in patients with mild cognitive impairment due to semantic dementia using resting‐state functional MRI.MethodsWe administered a battery of neuropsychological tests to twenty‐two patients with mild cognitive impairment due to semantic dementia (MCI‐SD group) and nineteen healthy controls (HC group). We performed structural MRI to compare gray matter volumes, and resting‐state functional MRI with multiple sub‐bands and indicators to evaluate functional activity.ResultsNeuropsychological tests revealed a significant decline in semantic performance in the MCI‐SD group, but no decline in other cognitive domains. Resting‐state functional MRI revealed local functional changes in multiple brain regions in the MCI‐SD group, distributed in different sub‐bands and indicators. In the normal band, local functional changes were only in the gray matter atrophic area. In the other sub‐bands, more regions with local functional changes outside atrophic areas were found across various indicators. Among these, the degree centrality of the left precuneus in the MCI‐SD group was positively correlated with general semantic tasks (oral sound naming, word‐picture verification).ConclusionOur study revealed local functional changes in mild cognitive impairment due to semantic dementia, some of which were located outside the atrophic gray matter. Driven by functional connectivity changes, the left precuneus might play a role in preclinical semantic dementia. The study proved the value of frequency‐dependent sub‐bands, especially the slow‐2 and slow‐3 sub‐bands.
Population pharmacokinetic analysis of apomorphine sublingual film or subcutaneous apomorphine in healthy subjects and patients with Parkinson’s disease
Authors: Agbo Felix , Crass Ryan L. , Chiu Yu‐Yuan , Chapel Sunny , Galluppi Gerald , Blum David , Navia Bradford 
Published: March 2021

AbstractApomorphine is an on‐demand treatment of “OFF” episodes in patients with Parkinson’s disease (PD). A joint parent‐metabolite population pharmacokinetic (PK) model characterized apomorphine and apomorphine‐sulfate following administration of apomorphine sublingual film (APL) and two formulations of subcutaneous apomorphine. Overall, 2485 samples from 87 healthy subjects and 71 patients with PD and “OFF” episodes were analyzed using nonlinear mixed‐effects modeling. Apomorphine PK was adequately described by a two‐compartment model with first‐order transit absorption via both routes of administration and first‐order metabolism to apomorphine‐sulfate with one‐compartment disposition and first‐order elimination. Bioavailability of apomorphine sublingual film was ~ 18% relative to subcutaneous apomorphine. Among covariates tested, only body weight had a large effect on apomorphine exposure (maximum plasma concentration and area under the concentration–time curve [AUC0–∞]), with greater weight resulting in lower exposure. Model‐predicted apomorphine exposure was similar between apomorphine sublingual film 30 mg and subcutaneous apomorphine 5 mg (median AUC0–24, 66.7 ng•h/mL, geometric mean ratio of 0.99; 90% confidence interval [CI], 0.96−1.03) and was comparable between apomorphine sublingual film 35 mg and subcutaneous apomorphine 6 mg (median AUC0–24, 75.4 and 80.0 ng•h/mL, respectively; geometric mean ratio of 0.94; 90% CI, 0.90−0.97) administered every 2 h for a maximum of 5 doses per day. In a typical patient with PD, predicted apomorphine exposure increased with increasing doses of apomorphine sublingual film; however, the increase was less than dose proportional. Similar apomorphine exposure was predicted in patients with mild renal impairment versus normal renal function. PK properties of apomorphine sublingual film support its administration for a wide range of patients with PD and “OFF” episodes, regardless of demographic and clinical characteristics.
Introducing alcohol as a drug in medicine reviews with pharmacists: Findings from a co‐design workshop with patients
Authors: Madden Mary , Morris Stephanie , Ogden Margaret , Lewis David , Stewart Duncan , O'Carroll Ronan E. , McCambridge Jim 
Published: March 2021

AbstractIntroductionAlcohol poses a range of potential problems to people taking medications, but health professionals are usually not comfortable talking about drinking with patients. The Medicines and Alcohol Consultation aims to increase the capacity of pharmacists to conduct person‐centred reviews in which alcohol is regarded as another drug to be discussed alongside medications. This paper explores sensitivities in discussing alcohol and views on the legitimacy of the Medicines and Alcohol Consultation intervention concept at a pharmacy‐user intervention co‐design workshop.MethodsA co‐design workshop was held with 14 people recruited from UK community pharmacies who regularly drank alcohol and took medications for long‐term conditions. This formed one element of a broader, iterative, intervention co‐production process. Workshop discussions were audio‐recorded and analysed thematically.ResultsThe basic intervention concept resonated well, though not entirely unproblematically. Participants were interested in receiving information on how medications interact with alcohol and how this might affect their own conditions, with which to make their own informed choices. Linking alcohol use to medicines gave legitimacy to pharmacists to raise alcohol in medicines reviews. Sensitivity in talking about alcohol was linked to vulnerability to negative judgement.Discussion and ConclusionsChanging the framing of alcohol in medicines reviews, away from being regarded as a ‘lifestyle issue’ to being considered a drug directly linked to medicines use, safety and effectiveness, was welcomed by participants in this study.
Therapeutic inertia in the management of dyslipidaemia and hypertension in incident type 2 diabetes and the resulting risk factor burden: Real‐world evidence from primary care
Authors: Ling Joanna Z.J. , Montvida Olga , Khunti Kamlesh , Zhang Anthony L. , Xue Charlie C. , Paul Sanjoy K. 
Published: March 2021

AbstractObjectiveTo investigate trends in the prevalence of hypertension and dyslipidaemia in incident type 2 diabetes (T2DM), time to antihypertensive (AHT) and lipid‐lowering therapy (LLT), and the association with systolic blood pressure (SBP) and lipid control.Research Design and MethodsUsing The Health Improvement Network UK primary care database, 254 925 people with incident T2DM and existing dyslipidaemia or hypertension were identified. Among those without atherosclerotic cardiovascular disease (ASCVD) history and not on AHT or LLT at diagnosis, the adjusted median months to initiating an AHT or an LLT, and the probabilities of high SBP or lipid levels over 2 years in people initiating therapy within or after 1 year were evaluated according to high and low ASCVD risk status.ResultsAt diabetes diagnosis, 66% and 66% had dyslipidaemia and hypertension, respectively. During 2005 to 2016, dyslipidaemia prevalence increased by 10% in people aged <60 years, while hypertension prevalence remained stable in all age groups. Among those with high ASCVD risk status in the age groups 18 to 39, 40 to 49, and 50 to 59 years, the median number of months to initiation of therapy were 20.4 (95% confidence interval [CI] 20.3‐20.5), 10.9 (95% CI 10.8‐11.0), and 9.5 (95% CI 9.4‐9.6) in the dyslipidaemia subcohort, and 28.1 (95% CI 28.0‐28.2), 19.2 (95% CI 19.1‐19.3), and 19.9 (95% CI 19.8‐20.0) in the hypertension subcohort. Among people with high and low ASCVD risk status, respectively, compared to early LLT initiators, those who initiated LLT after 1 year had a 65.3% to 85.3% and a 65.0% to 85.3% significantly higher probability of failing lipid control at 2 years of follow‐up, while late AHT initiators had a 46.5% to 57.9% and a 40.0% to 58.7% significantly higher probability of failing SBP control.ConclusionsSignificant delay in initiating cardioprotective therapies was observed, and time to first prescription was similar in the primary prevention setting, irrespective of ASCVD risk status across all T2DM diagnosis age groups, resulting in poor risk factor control at 2 years of follow‐up.
Dispersal–reproduction trade‐off in the leaf beetleGalerucella grisescens
Authors: Nasu Shota , Tokuda Makoto 
Published: March 2021

AbstractDispersion–reproduction trade‐offs are important to explore the evolutionary mechanism of dispersal strategies and the adaptive significance of dispersion in insects. In our previous study, variations in hindwing length were found in Japanese populations of the leaf beetleGalerucella grisescens(Joannis) (Coleoptera: Chrysomelidae). They were distinctly divided into either long‐winged (LW) or short‐winged (SW) morphs in the field. The LW morphs were distributed widely in Japan, whereas the SW morphs were found in restricted areas in Honshu, the main island of Japan. We examined the possible existence of trade‐offs between dispersion and reproduction inG.grisescensby laboratory experiments. Larval duration and adult body size (head width) were not significantly different between LW and SW strains, but adult body weight was larger in some LW strains than in SW strains, most likely due to the size of hindwings and legs as well as to the development of flight muscles. Although the pre‐oviposition period was not significantly different among strains, female longevity and fertility were significantly higher in SW than in LW strains. Long‐winged individuals displayed flutter behaviours, suggesting their flight dispersal abilities, but SW individuals did not. Femurs of LW individuals were significantly longer on all legs compared to SW strains and the former walked faster than the latter. The present results indicate the presence of a dispersion–reproduction trade‐off inG. grisescens, in which SW strains have advantages in reproductive abilities and LW strains in dispersal abilities.
Physical activity in hemodialysis patients on nondialysis and dialysis days: Prospective observational study
Authors: Malhotra Rakesh , Kumar Ujjala , Virgen Patricia , Magallon Bryan , Garimella Pranav S. , Chopra Tushar , Kotanko Peter , Ikizler T. Alp , Trzebinska Danuta , Cadmus‐Bertram Lisa , Ix Joachim H. 
Published: March 2021

AbstractIntroductionThe physical decline in patients with end‐stage kidney disease (ESKD) is associated with morbidity and mortality. Prior studies have attempted to promote physical activity at the time of dialysis; however, physical activity patterns on the nondialysis days are unknown. This study aimed to quantify physical activity on dialysis and nondialysis days in hemodialysis patients using a wearable actigraph.MethodsIn this prospective study, subjects receiving hemodialysis were recruited from two outpatient dialysis units in urban San Diego and rural Imperial County, CA, between March 2018 and April 2019. Key inclusion criteria included: (1) receiving thrice weekly hemodialysis for ≥3 months, (2) age ≥ 18 years, and (3) able to walk with or without assistive devices. All participants wore a Fitbit Charge 2 tracker for a minimum of 4 weeks. The primary outcome was the number of steps per day. Each participant completed the Physical Activity Questionnaire, the Patient Health Questionnaire (PHQ)‐9, the PROMIS Short form Fatigue Questionnaire at baseline, and the Participant Technology Experience Questionnaire at day 7 after study enrolment.FindingsOf the 52 recruited, 45 participants (urban = 25; rural = 20) completed the study. The mean age was 61 ± 15 years, 42% were women, 64% were Hispanic, and the mean dialysis vintage was 4.4 ± 3.0 years. For those with valid Fitbit data (defined as ≥10 hours of wear per day) for 28 days (n = 45), participants walked an average of 3688 steps per day, and 73% of participants were sedentary (<5000 steps/day). Participants aged >80 years were less active than younger (age < 65 years) participants (1232 vs. 4529 steps, P = 0.01). There were no statistical differences between the groups when stratified by gender (women vs. men [2817 vs. 4324 steps, respectively]), urbanicity (rural vs. urban dialysis unit [3141 vs. 4123 steps, respectively]), and dialysis/nondialysis day (3177 vs. 4133 steps, respectively). Due to the small sample size, we also calculated effect sizes. The effect size was medium for the gender differences (cohen's d = 0.57) and small to medium for urbanicity and dialysis/nondialysis day (d = 0.37 and d = 0.33, respectively). We found no association between physical activity and self‐reported depression and fatigue scale. The majority of participants (62%, 28/45) found the Fitbit tracker easy to wear and comfortable.DiscussionESKD participants receiving hemodialysis are frequently sedentary, and differences appear more pronounced in older patients. These findings may assist in designing patient‐centered interventions to increase physical activity among hemodialysis patients.
Aspirin and pre‐eclampsia prevention in women with pre‐existing diabetes: a retrospective study
Authors: Lah Siehoon , Cheung N Wah , Lee Vincent , Athayde Neil , Inglis Emma , Padmanabhan Suja 
Published: March 2021

AbstractBackgroundAspirin is routinely prescribed in high‐risk pregnancies to prevent pre‐eclampsia; however, there is a paucity of data in women with pre‐existing diabetes.AimsTo assess the efficacy and safety of aspirin in women with pre‐existing diabetes in preventing pre‐eclampsia.MethodsA retrospective review of women with pre‐existing diabetes who attended antenatal clinics in a tertiary referral hospital between 2013 and 2019 was conducted. Cases were those receiving aspirin prior to 16 weeks, with pre‐eclampsia as the primary outcome. The relationship between early pregnancy glycaemic control and pre‐eclampsia was also assessed.ResultsOf the 164 women included in the study, 45 received aspirin. There were no differences in pre‐eclampsia (odds ratio (OR) 0.9 (0.3–3.0), P = 0.924) or any other measure of placental insufficiency (OR 1.7 (0.7–4.3), P = 0.243) between the aspirin and control groups after adjusting for baseline differences. Aspirin therapy was associated with an increased risk of postpartum haemorrhage (PPH) (OR 3.1 (1.1–9.1), P = 0.041). The incidence of pre‐eclampsia increased stepwise according to early pregnancy HbA1c subgroups of ≤6.0% (n = 47), 6.1–7.5% (n = 57) and > 7.5% (n = 39), with rates of 0, 12.3 and 20.5% (P = 0.007) respectively.ConclusionsThe aspirin group had a higher baseline risk of pre‐eclampsia and placental insufficiency, therefore the absence of difference between the groups favoured the efficacy of aspirin. PPH was highlighted as a potential complication of therapy, and early pregnancy HbA1c as a novel risk stratification tool for pre‐eclampsia in women with pre‐existing diabetes.
Valence‐induced effects on the electrical properties of NiMn2O4 ceramics with different Ni sources
Authors: Guan Fang , Wu Yiquan , Milisavljevic Iva , Cheng Xin , Huang Shifeng 
Published: March 2021

AbstractSpinel‐structured NiMn2O4 ceramics, with different valence Ni sources, were originally prepared using Ni2O3 and NiO as raw materials, and the effects of different valence Ni sources on their electrical properties were first investigated. XRD patterns show that both Ni2O3‐based and NiO‐based NiMn2O4 ceramics are single cubic spinel structures. SEM/EDS images indicate that the NiMn2O4 ceramics exhibited high density at the experiment‐determined sintering temperatures. XPS results and Raman drifts prove that the Ni valence‐induced changes in Mn ions at B sites played a significant role in the electrical properties and thermal stability of NiMn2O4 ceramics. Compared with NiO‐based NiMn2O4, the resistivity at 25°C (ρ25°C) of Ni2O3‐based NiMn2O4 increased dramatically from 3109 to 106958 Ω cm, the thermal constant (B25/50) increased from 3264 to 4473 K, and the resistance shifts after annealing for 1000 h at 150°C decreased from 0.80% to 0.74%. The investigation of the relationship between the material properties and valence of Ni sources has provided a new and effective way for designing the spinel‐structured negative temperature coefficient (NTC) materials by modulating the valence of ions at A sites in the raw materials.