Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigating the performance of 24-h urinary sucrose and fructose as a biomarker of total sugars intake in US participants - a controlled feeding study.

BACKGROUND Developing approaches for the objective assessment of sugars intake in population research is crucial for generating reliable disease risk estimates, and evidence-based dietary guidelines. Twenty-four-hour urinary sucrose and fructose (24uSF) was developed as a predictive biomarker of total sugars intake based on 3 UK feeding studies, yet its performance as a biomarker of total sugars among US participants is unknown. OBJECTIVES To investigate the performance of 24uSF as a biomarker of sugars intake among US participants, and to characterize its use. METHODS Ninety-eight participants, aged 18-70 y, consumed their usual diet under controlled conditions of a feeding study for 15 d, and collected 8 nonconsecutive 24-h urines measured for sucrose and fructose. RESULTS A linear mixed model regressing log 24uSF biomarker on log total sugars intake along with other covariates explained 56% of the biomarker variance. Total sugars intake was the strongest predictor in the model (Marginal R2 = 0.52; P <0.0001), followed by sex (P = 0.0002) and log age (P = 0.002). The equation was then inverted to solve for total sugars intake, thus generating a calibrated biomarker equation. Calibration of the biomarker produced mean biomarker-based log total sugars of 4.79 (SD = 0.59), which was similar to the observed log 15-d mean total sugars intake of 4.69 (0.35). The correlation between calibrated biomarker and usual total sugars intake was 0.59 for the calibrated biomarker based on a single biomarker measurement, and 0.76 based on 4 biomarker repeats spaced far apart. CONCLUSIONS In this controlled feeding study, total sugars intake was the main determinant of 24uSF confirming its utility as a biomarker of total sugars in this population. Next steps will include validation of stability assumptions of the biomarker calibration equation proposed here, which will allow its use as an instrument for dietary validation and measurement error correction in diet-disease association studies.
Characterizing spatial gene expression heterogeneity in spatially resolved single-cell transcriptomic data with nonuniform cellular densities

Recent technological advances have enabled spatially resolved measurements of expression profiles for hundreds to thousands of genes in fixed tissues at single-cell resolution. However, scalable computational analysis methods able to take into consideration the inherent 3D spatial organization of cell types and nonuniform cellular densities within tissues are still lacking. To address this, we developed MERINGUE, a computational framework based on spatial autocorrelation and cross-correlation analysis to identify genes with spatially heterogeneous expression patterns, infer putative cell–cell communication, and perform spatially informed cell clustering in 2D and 3D in a density-agnostic manner using spatially resolved transcriptomic data. We applied MERINGUE to a variety of spatially resolved transcriptomic data sets including multiplexed error-robust fluorescence in situ hybridization (MERFISH), spatial transcriptomics, Slide-seq, and aligned in situ hybridization (ISH) data. We anticipate that such statistical analysis of spatially resolved transcriptomic data will facilitate our understanding of the interplay between cell state and spatial organization in tissue development and disease.
Children with under-diagnosed asthma presenting to a pediatric emergency department

Abstract Background Undiagnosed asthma in children presenting to the emergency department (ED) for respiratory illnesses might be associated with subsequent asthma morbidity and repeat ED visits. Objective To examine the prevalence of undiagnosed asthma among children presenting for ED care, and explore associations with sociodemographic and clinical characteristics. Methods We surveyed parents of children ages 2–17 years seeking ED care for respiratory symptoms (including asthma) regarding sociodemographic characteristics, asthma symptoms, prior asthma care and morbidity, and prior asthma diagnosis. Undiagnosed asthma was defined as a positive screening for asthma and no prior diagnosis. We compared sociodemographic and clinical factors of those with diagnosed versus undiagnosed asthma using chi-square, t-tests and multivariable logistic regression model. Results Of 362 children, 36% had undiagnosed asthma. Undiagnosed children were younger, had younger parents, and had parents less likely to speak English versus diagnosed children (all p < 0.05). Among undiagnosed children, 42% had moderate or severe asthma and 66% reported ≥1 exacerbation in the prior 12 months. Parent-reported controller medication use was higher among diagnosed versus undiagnosed children (60% vs. 21%, p=.001). In a multivariable logistic regression (adjusting for insurance, education, income and preferred language), no controller usage (aOR 4.26), no asthma exacerbations in the prior year (aOR 2.41) and younger age (aOR 0.76) were significantly associated with undiagnosed asthma. Conclusion Children presenting to the ED with undiagnosed asthma commonly experience significant prior asthma morbidity. Strategies to improve asthma diagnosis and messaging to their parents may reduce future morbidity.
Life-course trajectories of working conditions and successful ageing

Aims: As populations are ageing worldwide, it is important to identify strategies to promote successful ageing. We investigate how working conditions throughout working life are associated with successful ageing in later life. Methods: Data from two nationally representative longitudinal Swedish surveys were linked (n=674). In 1991, respondents were asked about their first occupation, occupations at ages 25, 30, 35, 40, 45 and 50 years and their last recorded occupation. Occupations were matched with job exposure matrices to measure working conditions at each of these time points. Random effects growth curve models were used to calculate intra-individual trajectories of working conditions. Successful ageing, operationalised using an index including social and leisure activity, cognitive and physical function and the absence of diseases, was measured at follow-up in 2014 (age 70 years and older). Multivariable ordered logistic regressions were used to assess the association between trajectories of working conditions and successful ageing. Results: Intellectually stimulating work; that is, substantive complexity, in the beginning of one’s career followed by an accumulation of more intellectually stimulating work throughout working life was associated with higher levels of successful ageing. In contrast, a history of stressful, hazardous or physically demanding work was associated with lower levels of successful ageing. Conclusions: Promoting a healthy workplace, by supporting intellectually stimulating work and reducing physically demanding and stressful jobs, may contribute to successful ageing after retirement. In particular, it appears that interventions early in one’s employment career could have positive, long-term effects.
Ecological engineering across a temporal gradient: sociable weaver colonies create year-round animal biodiversity hotspots.

Animal distribution in a landscape depends mostly on the availability of resources. This can be facilitated by other species that have positive effects on local species diversity and impact community structure. Species that significantly change resource availability are often termed ecosystem engineers. Identifying these species is key but predicting where they have large or small impacts is an even greater challenge. The stress-gradient hypothesis predicts that the importance of facilitative interactions that shape community structure and function will increase in stressful and harsh environments. In most environments, conditions will fluctuate between harsh and benign periods, yet how the impacts of ecosystem engineers will change in different conditions has received little attention. Monitoring for extended periods will increase the understanding of how engineers may mitigate the extreme differences between changing seasons. We investigated the role of sociable weavers (Philetairus socius) as ecosystem engineers and examined how the association of species to weaver colonies may vary across a seasonal (temporal) gradient. Sociable weavers build large colonies that are home to hundreds of weaver individuals but also host a wide range of other animal species. We investigated the use of weaver colonies by terrestrial and arboreal vertebrates and birds throughout a calendar year, encompassing harsh and benign periods. We demonstrate that the presence of sociable weaver colonies creates centres of animal activity. Colonies were used by the local Kalahari animal community for foraging, shade, territorial behaviours and roosting sites. Furthermore, animal activity increased with increased primary productivity, but this was not restricted to weaver colonies, suggesting that the importance of colonies does not directionally change across environmental conditions. Our results were not consistent with predictions of the stress-gradient hypothesis across a temporal gradient. We demonstrate the importance of sociable weavers as ecological engineers and the significance of their colonies in structuring the surrounding animal community. Colonies appear to provide a range of different resources for different species. Sociable weaver colonies have large ecological importance to local animal communities and, by mitigating environmental stress, may be increasingly important as human-driven climate change advances.
Surgery for brain metastases – real-world prognostic factors’ association with survival

Abstract Background Surgical resection of brain metastases (BM) improves overall survival (OS) in selected patients. Selecting those patients likely to benefit from surgery is challenging. The Graded Prognostic Assessment (GPA) and the diagnosis-specific Graded Prognostic Assessment (ds-GPA) were developed to predict survival in patients with BM, but not specifically to guide patient selection for surgery. Our aim was to evaluate the feasibility of preoperative GPA/ds-GPA scores and assess variables associated with OS. Methods We retrospectively reviewed first-time surgical resection of BM from solid tumors at a Norwegian regional referral center from 2011 to 2018. Results Of 590 patients, 51% were female and median age was 63 years. Median OS was 10.3 months and 74 patients (13%) died within three months after surgery. Preoperatively tumor origin was unknown in 20% of patients. A GPA score could be calculated for 92% of the patients preoperatively, but could not correctly predict survival. A ds-GPA score could be calculated for 46% of patients. Multivariable regression analysis revealed shorter OS in patients with higher age, worse functioning status, colorectal primary cancer compared to lung cancer, presence of extracranial metastases, and more than four BM. Patients with preoperative progressive extracranial disease or synchronous BM had shorter OS compared to patients with stable extracranial disease. Conclusion Ds-GPA could be calculated in less than half of patients preoperatively and GPA poorly identified patients which had minimal benefit of surgery. Including status of extracranial disease improve prognostication and therefore selection to surgery for brain metastases.
Erythrocyte Long-Chain ω-3 Fatty Acids Are Positively Associated with Lean Mass and Grip Strength in Women with Recent Diagnoses of Breast Cancer.

BACKGROUND Sarcopenia may hasten the risk of mortality in women with breast cancer. Long-chain omega-3 (n-3) polyunsaturated fatty acids (LCn-3PUFAs) may favor muscle mass which, in turn, could enhance resilience of cancer patients toward cancer treatment. OBJECTIVES The objective of this study was to measure the relation of erythrocyte LCn-3PUFA concentrations with lean mass, grip strength, and postprandial energy metabolism in women with newly diagnosed breast cancer. METHODS This cross-sectional analysis evaluated women (n = 150) ages 65 y and younger who were recently diagnosed with breast cancer (stages I-III). Erythrocyte LCn-3PUFA composition was measured using GC. Body composition was measured by DXA. Grip strength was assessed at the same visit. Postprandial energy metabolism was measured for 7.5 h after the consumption of a high-calorie, high-saturated-fat test meal using indirect calorimetry. Associations of fatty acids with outcomes were analyzed using multiple linear regression models and linear mixed-effects models. RESULTS The ω-3 index, a measurement of LCn-3PUFA status, was positively associated with appendicular lean mass (ALM)/BMI (β = 0.015, P = 0.01) and grip strength (β = 0.757, P = 0.04) after adjusting data for age and cancer stage. However, when cardiorespiratory fitness was also included in the analyses, these relations were no longer significant (P > 0.08). After a test meal, a higher ω-3 index was associated with a less steep rise in fat oxidation (P = 0.02) and a steeper decline in glucose (P = 0.01) when adjusting for age, BMI, cancer stage, and cardiorespiratory fitness. CONCLUSIONS The ω-3 index was positively associated with ALM/BMI and grip strength in women newly diagnosed with breast cancer and was associated with altered postprandial substrate metabolism. These findings warrant further studies to determine whether enriching the diet with LCn-3PUFAs during and after cancer treatments is causally linked with better muscle health and metabolic outcomes in breast cancer survivors.
Cardiovascular risk factors of Alzheimer's disease and other neurocognitive disorders in Malaysia.

INTRODUCTION Risk factors for cardiovascular disease (CVD) have been increasingly implicated in the development of dementia but little is known about the effects in a Malaysian population. We aimed to determine the interaction between sociodemographic and CVD risk factors among the dementia and mild cognitive impairment (MCI) patients in Malaysia. MATERIALS AND METHODS A cross-sectional study was conducted in the memory clinic at Hospital Kuala Lumpur (HKL). Medical records data from 2014 to 2019 were extracted. Mini Mental State Examination (MMSE) test was used to assess the neurocognitive function of patients. RESULTS A total of 298 patients (30 MCI, and 268 dementia) were evaluated, with dementia patients consisting of 78 Alzheimer's disease (AD), 93 Vascular dementia (VaD), 94 Mixed dementia, 2 early-onset Alzheimer's disease (EOAD) and 1 Logopenic Progressive Aphasia type of AD (LPA). MCI and dementia were significantly associated with a history of CVD, particularly stroke (p=0.023). CONCLUSION Given that stroke significantly predicted the risk of developing vascular dementia among the patients in a central Malaysian population, lifestyle modifications are recommended to alleviate these risk factors of CVD.
Increasing Biosimilar Utilization at a Pediatric Inflammatory Bowel Disease Center and Associated Cost Savings: Show Me the Money.

BACKGROUND Tumor necrosis factor-alpha inhibitors (anti-TNFs) are a primary treatment for inflammatory bowel disease. Pharmaceutical expenditures and usage of specialty drugs are increasing. In the United States, biosimilars continue to be underutilized, despite opportunities for health care cost savings. Through quality improvement (QI) methodology, we aimed to increase biosimilar utilization among eligible patients initiating intravenous (IV) anti-TNF therapy and describe patient outcomes and associated cost savings. METHODS Beginning in July 2019, all patients initiating IV anti-TNF therapy were identified and tracked. Using the Institute of Healthcare Improvement Plan-Do-Study-Act cycle, a four-stage problem-solving model used for carrying out change, we trialed interventions to increase biosimilar utilization, including provider, staff, and family education, and utilization of a clinical pharmacist and insurance specialist. Statistical process control charts were used to show improvement over time. Patients' clinical outcome and cost savings were reviewed. RESULTS Using QI methodology, we increased biosimilar utilization from a baseline of 1% in June 2019 to 96% by February 2021, with sustained improvement. The originator (infliximab) was the insurance company's preferred product for 20 patients (20%). Patient outcomes (IV anti-TNF levels, absence of antidrug antibodies, and physician global assessment) between biosimilars and originators were similar. Estimated cost savings over the project duration were nearly $381,000 (average sales price) and $651,000 (wholesale acquisition cost). CONCLUSIONS Through QI methodology, we increased biosimilar utilization from 1% to 96% with sustained improvement, without compromising patient outcomes or safety. Estimated cost savings were substantial. Similar methodology could be implemented at other institutions to increase biosimilar utilization and potentially decrease health care costs.
Silver nanoparticles offer a synergistic effect with fluconazole against fluconazole-resistant Candida albicans by abrogating drug efflux bumps and increasing endogenous ROS.

OBJECTIVES A frequent emergence of drug resistance has been observed and posed great threat to global public health recently. This work aimed to investigate the potential synergistic effect and the underlying mechanisms of AgNPs-fluconazole combination more extensively through 2 clinically isolated fluconazole-resistant Candida albicans (C. albicans) strains. METHODS Antifungal properties of AgNPs and fluconazole alone or together against planktonic cells and biofilms were tested. Cellular and molecular targets associated with fluconazole resistance were monitored after AgNPs treatment. Antifungal potential of AgNPs-fluconazole combination was also explored in vivo using a mouse model of disseminated candidiasis. Tissue burden and survival rate were analyzed. RESULTS The results indicated that AgNPs worked synergistically with fluconazole against both planktonic cells of fluconazole-resistant C. albicans and biofilms formed <12 h. AgNPs treatment down-regulated ERG1, ERG11, ERG25, and CDR2, decreased membrane ergosterol levels and membrane fluidity, reduced membrane content of Cdr1p, Cdr2p, and thus efflux bump activity. The elevated ROS production was also a likely cause of the synergistic effect. In vivo, AgNPs and fluconazole combination significantly decreased the fungal burden and improved the survival rate of infected mice. CONCLUSION In conclusion, these results further confirm that AgNPs-fluconazole combination is a hopeful strategy for the treatment of fluconazole-resistant fungal infections.
Systemic NF-κB-mediated inflammation promotes an aging phenotype in skeletal stem/progenitor cells

Aging tissues undergo a progressive decline in regenerative potential. This decline in regenerative responsiveness has been attributed to changes in tissue-specific stem cells and their niches. In bone, aged skeletal stem/progenitor cell dysfunction is characterized by decreased frequency and impaired osteogenic differentiation potential. This aging phenotype ultimately results in compromised regenerative responsiveness to injury. The age-associated increase of inflammatory mediators, known as inflamm-aging, has been identified as the main culprit driving skeletal stem cell dysfunction. Here, we utilized a mouse model of parabiosis to decouple aging from inflammation. Using the Nfkb1-/- mouse as a model of inflamm-aging, we demonstrate that a shared systemic circulation between a wild-type and Nfkb1-/- mouse results in an aging phenotype of the wild-type skeletal stem and progenitor cells, shown by CFU-fs and osteogenic and adipogenic differentiation assays. Our findings demonstrate that exposure to an inflammatory secretome results in a phenotype similar to the one observed in aging.
Permeation selectivity of pristine and vacancy defected hexagonal boron membranes for alkaline earth metal and ions

Abstract Permeation and selectivity of alkaline metal atoms and ions through normal and defected hexagonal boron nitride is explored in the presence and absence of water. The defects include one (V B and V N), two (V BN) and three atoms (V B(2N) and V N(2B)) vacancies. The barriers are obtained by scanning potential energy surface for the movement of alkaline earth metal atoms and ions through the nanosheet. The size and morphology of defects in h-BN sheet significantly affect the energy barrier. h-BN sheet with V N defect possess good Be/Be2+ selectivity. Permeation of Be atoms through V BN-h-BN, V B(2N)-h-BN and V N(2B) -h-BN is a barrierless process. Mostly, the permeation barriers are reduced in the presence of water molecule for Be, Ca and Ca2+. The effect of water molecule is more pronounced on the permeation of Ca atom and ion through normal and defected h-BN sheet as compared to smaller alkaline earth metal atoms and ions. The study can be extended to investigate the separation capability of porous hexagonal boron nitride nanosheet for other metal atoms and ions. Highlights Permeability of pristine and vacancy defected h-BN nanosheet is studied for alkaline earth metal atoms and ions. Increase in pore size and applied electric field decrease the permeation barriers for alkaline earth metal atoms and ions. V N h-BN sheet possess good Be/Be2+ selectivity. Permeation of Be atoms through V BN-h-BN, V B(2N)-h-BN and V N(2B) -h-BN is a barrierless process. Permeation barriers are reduced in the presence of water molecule for Be, Ca and Ca2+. Communicated by Ramaswamy H. Sarma
Ain’t Just Imagination! Effects of Motor Imagery Training on Strength and Power Performance of Athletes during Detraining

Supplemental digital content is available in the text. ABSTRACT Purpose This study aimed to investigate the effects of motor imagery (MI) training on strength and power performances of professional athletes during a period of detraining caused by the COVID-19 outbreak. Methods Thirty male professional basketball players (age, 26.1 ± 6.2 yr) were randomly assigned to three counterbalanced groups: two MI training groups, who completed imagery training by mentally rehearsing upper and lower limb resistance training exercises loaded with either 85% of one repetition maximum (85%1RM) or optimum power loads (OPL), or a control group. For six consecutive weeks, although all groups completed two weekly sessions of high-intensity running, only the MI groups performed three additional MI sessions a week. Maximal strength and power output were measured through 1RM and OPL assessments in the back squat and bench press exercises with a linear positioning transducer. Vertical jump and throwing capabilities were assessed with the countermovement jump and the seated medicine ball throw tests, respectively. Kinesthetic and visual imagery questionnaires, and chronometry and rating of perceived effort scores were collected to evaluate MI vividness, MI ability, and perceived effort. Results Physical performances improved significantly following both MI protocols (range, ~2% to ~9%), but were reduced in the control group, compared with preintervention (P ≤ 0.016). Moreover, interactions (time–protocol) were identified between the two MI groups (P ≤ 0.001). Whereas the 85%1RM led to greater effects on maximal strength measures than the OPL, the latter induced superior responses on measures of lower limb power. These findings were mirrored by corresponding cognitive and psychophysiological responses. Conclusions During periods of forced detraining, MI practice seems to be a viable tool to maintain and increase physical performance capacity among professional athletes.