Miracle-dz/UniFAR-FTUs huggingface dataset:
Biomarkers for Alzheimer's disease: current status and prospects for the future

Accumulating data from the clinical research support that the core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid‐β (Aβ42), total tau (T‐tau), and phosphorylated tau (P‐tau) reflect key elements of AD pathophysiology. Importantly, a large number of clinical studies very consistently show that these biomarkers contribute with diagnostically relevant information, also in the early disease stages. Recent technical developments have made it possible to measure these biomarkers using fully automated assays with high precision and stability. Standardization efforts have given certified reference materials for CSF Aβ42, with the aim to harmonize results between assay formats that would allow for uniform global reference limits and cut‐off values. These encouraging developments have led to that the core AD CSF biomarkers have a central position in the novel diagnostic criteria for the disease and in the recent National Institute on Aging and Alzheimer's Association biological definition of AD. Taken together, this progress will likely serve as the basis for a more general introduction of these diagnostic tests in clinical routine practice. However, the heterogeneity of pathology in late‐onset AD calls for an expansion of the AD CSF biomarker toolbox with additional biomarkers reflecting additional aspects of AD pathophysiology. One promising candidate is the synaptic protein neurogranin that seems specific for AD and predicts future rate of cognitive deterioration. Further, recent studies bring hope for easily accessible and cost‐effective screening tools in the early diagnostic evaluation of patients with cognitive problems (and suspected AD) in primary care. In this respect, technical developments with ultrasensitive immunoassays and novel mass spectrometry techniques give promise of biomarkers to monitor brain amyloidosis (the Aβ42/40 or APP669‐711/Aβ42 ratios) and neurodegeneration (tau and neurofilament light proteins) in plasma samples, but future studies are warranted to validate these promising results further.
Patterns and Trends in Cancer Screening in the United States

Introduction We examined the prevalence of cancer screening reported in 2015 among US adults, adjusted for important sociodemographic and access-to-care variables. By using data from the National Health Interview Survey (NHIS) for 2000 through 2015, we examined trends in prevalence of cancer screening that adhered to US Preventive Services Task Force screening recommendations in order to monitor screening progress among traditionally underserved population subgroups. Methods We analyzed NHIS data from surveys from 2000 through 2015 to estimate prevalence and trends in use of recommended screening tests for breast, cervical, colorectal, and prostate cancers. We used logistic regression and report predictive margins for population subgroups adjusted for various socioeconomic and demographic variables. Results Colorectal cancer screening was the only test that increased during the study period. We found disparities in prevalence of test use among subgroups for all tests examined. Factors that reduced the use of screening tests included no contact with a doctor in the past year, no usual source of health care, and no insurance coverage. Conclusion Understanding use of cancer screening tests among different population subgroups is vital for planning public health interventions with potential to increase screening uptake and reduce disparities in cancer morbidity and mortality. Overarching goals of Healthy People 2020 are to “achieve health equity, eliminate disparities, and improve the health of all groups. ” Adjusted findings for 2015, compared with previous years, show persistent screening disparities, particularly among the uninsured, and progress for colorectal cancer screening only.
Emergency Medicine Faculty Are Poor at Predicting Burnout in Individual Trainees: An Exploratory Study

Burnout is common among emergency medicine (EM) physicians, and it is prevalent even among EM trainees. Recently proposed Accreditation Council for Graduate Medical Education requirements encourage faculty to alert residency leadership when trainees display signs of burnout. It remains uncertain how trainees experiencing burnout can be reliably identified. We examined if EM faculty advisers at one institution can accurately predict burnout in their EM resident advisees.
Predictors for Prognosis in Patients With Nonfatal Pulmonary Embolism: A Registry-Based Cohort Study

The article’s aim was to determine predictors for short- and long-term prognosis of patients with pulmonary embolism (PE). Cohort prospective study based on the National registry on venous thromboembolism. Eighty-four patients with PE, on age 60.3 + 12.5 years, were selected and followed up in a prospective study. Pulmonary embolism was confirmed by computed tomography angiography in all the patients, while deep venous thrombosis was confirmed by ultrasound in 21 patients. Study population was followed up for 6.7 months. Multivariate regression analysis was done where right ventricular (RV) diameter (mean 37.5 mm), systolic pulmonary artery pressure (68 ± 23 mm Hg) measured by echocardiography, d-dimer level at baseline 2654.5 ± 420.3 ng/mL, number of comorbidities (2.4 ± 0.7), and present symptoms (3.1 ± 0.9) entered the model. The model was age-adjusted. d-dimer level was revealed as a predictor for the length of hospitalization (β = .25, P = .05) and RV diameter as a factor for duration of anticoagulation (β = .29, P = .05). Our results imply that the baseline measurement of these parameters independently influence both the short-term and long-term prognosis of patients with nonfatal PE.
Modifying Risks in Ventral Hernia Patients With Prehabilitation: A Randomized Controlled Trial

Objective: The aim of this study was to determine whether preoperative nutritional counseling and exercise (prehabilitation) in obese patients with ventral hernia repair (VHR) results in more hernia-free and complication-free patients. Background: Obesity and poor fitness are associated with complications following VHR. These issues are prevalent in low socioeconomic status patients. Methods: This was a blinded, randomized controlled trial at a safety-net academic institution. Obese patients (BMI 30 to 40) seeking VHR were randomized to prehabilitation versus standard counseling. VHR was performed once preoperative requirements were met: 7% total body weight loss or 6 months of counseling and no weight gain. Primary outcome was the proportion of hernia-free and complication-free patients. Secondary outcomes were wound complications at 1 month postoperative and weight loss measures. Univariate analysis was performed. Results: Among 118 randomized patients, prehabilitation was associated with a higher percentage of patients who lost weight and achieved weight loss goals; however, prehabilitation was also associated with a higher dropout rate and need for emergent repair. VHR was performed in 44 prehabilitation and 34 standard counseling patients. There was a trend toward less wound complication in prehabilitation patients (6.8% vs 17.6%, P = 0.167). The prehabilitation group was more likely to be hernia-free and complication-free (69.5% vs 47.5%, P = 0.015). Conclusions: It is feasible to implement a prehabilitation program for obese patients at a safety-net hospital. Prehabilitation patients have a higher likelihood of being hernia-free and complication-free postoperatively. Although further trials and long-term outcomes are needed, prehabilitation may benefit obese surgical patients, but there may be increased risks of dropout and emergent repair. Clinical Trial Registration: This trial was registered with clinicaltrials.gov (NCT02365194)
Icariin protects cardiomyocytes against ischaemia/reperfusion injury by attenuating sirtuin 1‐dependent mitochondrial oxidative damage

Icariin, a major active ingredient in traditional Chinese medicines, is attracting increasing attention because of its unique pharmacological effects against ischaemic heart disease. The histone deacetylase, sirtuin‐1, plays a protective role in ischaemia/reperfusion (I/R) injury, and this study was designed to investigate the protective role of icariin in models of cardiac I/R injury and to elucidate the potential involvement of sirtuin‐1.
Regional thalamic MRI as a marker of widespread cortical pathology and progressive frontotemporal involvement in amyotrophic lateral sclerosis

Background The thalamus is a major neural hub, with selective connections to virtually all cortical regions of the brain. The multisystem neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) has pathogenic overlap with frontotemporal dementia, and objective in vivo markers of extra-motor pathological spread are lacking. To better consider the role of the thalamus in neurodegeneration, the present study assessed the integrity of the thalamus and its connectivity to major cortical regions of the brain in a longitudinal manner. Methods Diffusion-based MRI tractography was used to parcellate the thalamus into distinct regions based on structural thalamo-cortical connectivity in 20 patients with ALS, half of whom were scanned at two time points, and 31 matched controls scanned on a single occasion. Results At baseline, widespread diffusivity alterations in motor- and extramotor-associated thalamic parcellations were detectable. Longitudinal decline selectively affected thalamic regions associated with frontal and temporal lobe connectivity. Diffusivity measures were significantly correlated with clinical measures of disease burden. Progression of functional disability, as indicated by change on the ALS functional rating scale, was associated with longitudinal change in mean diffusivity of the right frontal lobe thalamic parcellation (r=0.59, p=0.05). Conclusions Regional thalamic connectivity changes mirror the progressive frontotemporal cortical involvement associated with the motor functional decline in ALS. Longitudinal MRI thalamic parcellation has potential as a non-invasive surrogate marker of cortical dysfunction in ALS.
The plant compound rosmarinic acid induces a broad quorum sensing response in Pseudomonas aeruginosa PAO1

The interference of plant compounds with bacterial quorum sensing (QS) is a major mechanism through which plants and bacteria communicate. However, little is known about the modes of action and effects on signal integrity during this type of communication. We have recently shown that the plant compound rosmarinic acid (RA) specifically binds to the Pseudomonas aeruginosa RhlR QS receptor. To determine the effect of RA on expression patterns, we carried out global RNA-seq analysis. The results show that RA induces the expression of 128 genes, amongst which many virulence factor genes. RA triggers a broad QS response because 88% of the induced genes are known to be controlled by QS, and because RA stimulated genes were found to be involved in all four QS signalling systems within P. aeruginosa. This finding was confirmed through the analysis of transcriptional fusions transferred to wt and a rhlI/lasI double mutant. RA did not induce gene expression in the rhlI/lasI/rhlR triple mutant indicating that the effects observed are due to the RA-RhlR interaction. Furthermore, RA induced seven sRNAs that were all encoded in regions close to QS and/or RA induced genes. This work significantly enhances our understanding of plant bacteria interaction.
Risky business: linking Toxoplasma gondii infection and entrepreneurship behaviours across individuals and countries

Disciplines such as business and economics often rely on the assumption of rationality when explaining complex human behaviours. However, growing evidence suggests that behaviour may concurrently be influenced by infectious microorganisms. The protozoan Toxoplasma gondii infects an estimated 2 billion people worldwide and has been linked to behavioural alterations in humans and other vertebrates. Here we integrate primary data from college students and business professionals with national-level information on cultural attitudes towards business to test the hypothesis that T. gondii infection influences individual- as well as societal-scale entrepreneurship activities. Using a saliva-based assay, we found that students (n = 1495) who tested IgG positive for T. gondii exposure were 1.4× more likely to major in business and 1.7× more likely to have an emphasis in ‘management and entrepreneurship' over other business-related emphases. Among professionals attending entrepreneurship events, T. gondii-positive individuals were 1.8× more likely to have started their own business compared with other attendees (n = 197). Finally, after synthesizing and combining country-level databases on T. gondii infection from the past 25 years with the Global Entrepreneurship Monitor of entrepreneurial activity, we found that infection prevalence was a consistent, positive predictor of entrepreneurial activity and intentions at the national scale, regardless of whether previously identified economic covariates were included. Nations with higher infection also had a lower fraction of respondents citing ‘fear of failure' in inhibiting new business ventures. While correlational, these results highlight the linkage between parasitic infection and complex human behaviours, including those relevant to business, entrepreneurship and economic productivity.
Activity and Connectivity Differences Underlying Inhibitory Control Across the Adult Life Span

Inhibitory control requires precise regulation of activity and connectivity within multiple brain networks. Previous studies have typically evaluated age-related changes in regional activity or changes in interregional interactions. Instead, we test the hypothesis that activity and connectivity make distinct, complementary contributions to performance across the life span and the maintenance of successful inhibitory control systems. A representative sample of healthy human adults in a large, population-based life span cohort performed an integrated Stop-Signal (SS)/No-Go task during functional magnetic resonance imaging (n = 119; age range, 18–88 years). Individual differences in inhibitory control were measured in terms of the SS reaction time (SSRT), using the blocked integration method. Linear models and independent components analysis revealed that individual differences in SSRT correlated with both activity and connectivity in a distributed inhibition network, comprising prefrontal, premotor, and motor regions. Importantly, this pattern was moderated by age, such that the association between inhibitory control and connectivity, but not activity, differed with age. Multivariate statistics and out-of-sample validation tests of multifactorial functional organization identified differential roles of activity and connectivity in determining an individual's SSRT across the life span. We propose that age-related differences in adaptive cognitive control are best characterized by the joint consideration of multifocal activity and connectivity within distributed brain networks. These insights may facilitate the development of new strategies to support cognitive ability in old age. SIGNIFICANCE STATEMENT The preservation of cognitive and motor control is crucial for maintaining well being across the life span. We show that such control is determined by both activity and connectivity within distributed brain networks. In a large, population-based cohort, we used a novel whole-brain multivariate approach to estimate the functional components of inhibitory control, in terms of their activity and connectivity. Both activity and connectivity in the inhibition network changed with age. But only the association between performance and connectivity, not activity, differed with age. The results suggest that adaptive control is best characterized by the joint consideration of multifocal activity and connectivity. These insights may facilitate the development of new strategies to maintain cognitive ability across the life span in health and disease.
DUOX1‐mediated hydrogen peroxide release regulates sodium transport in H441 bronchiolar epithelial cells

Dexamethasone has been shown to induce the formation of epithelial domes by bronchiolar H441 cells. It stimulates the expression of both amiloride inhibitable epithelial sodium channels (ENaC) and dual oxidase‐1 (DUOX1). We therefore ask the question whether DUOX1 expression and production of submillimolar amounts of H2O2 is instrumental for the sodium channel upregulation observed in H441 cells.
Say cheese? The connections between positive facial expressions in student identification photographs and health care seeking behavior

This study examined whether positive facial expressions in student identification photographs were connected with a health-relevant behavior: visits to a health care center in the last year for preventive and non-preventive (e.g. illness, injury) purposes. Identification photographs were coded for degree of smile. Smiling participants were more likely to have sought preventive care versus those not smiling in their photographs, but there was no difference in non-preventive (i.e. ill health) visits. This study shows for the first time that smiling in photographs may be related to healthy behavior and complements past work connecting smiling to positive psychosocial and health outcomes.
Vascularized Plexus Allotransplantation: A New Hope in Brachial Plexus Palsy?

Brachial plexus injury is associated with significant disability, and can occur throughout life. Shoulder dystocia complicates 1% to 2% of births, of which approximately 20% result in brachial plexus palsy. Young adults have a higher incidence of penetrating trauma to the axilla or neck, as well as motorcycle accidents and low-velocity sporting injuries resulting in traction to the upper roots and trunks. Compression injuries, due to either malignancy or anatomic variations, such as cervical ribs or congenital fibrous bands, may also be implicated. Later in life, adjuvant radiotherapy to the axilla for treatment of breast carcinoma may also result in brachial plexopathy, manifesting anywhere from 6 months to 20 years after treatment. Severe plexus injuries rarely resolve spontaneously and were historically occasionally managed by amputation. The current standard of practice for treatment of severe brachial plexus injuries includes free muscle transfer, multiple nerve transfers, or nerve interposition grafts, with the primary goal of restoring elbow flexion, followed by shoulder stability and motility, and finally hand and wrist function. None of these options are without their limitations, however, be it donor site morbidity or simply limited availability of appropriate donor nerves (such as the sural ormedial antebrachial cutaneous) for interposition autografts. Furthermore, the challenging biology of nerve regeneration and the proximal level of these injuries have typically been associated with notoriously poor outcomes. There is a need for advanced surgical strategies with the potential for recovery of forearm and finger flexion in particular. In this issue of Transplantation, Chang et al describe a rat model of whole brachial plexus allogeneic interposition transplantation across a full major histocompatibility complex mismatch (RT1 to RT1). A vascularized neurocutaneous allograft composed of the brachial plexus, subclavian artery and vein, and sentinel skin patch was harvested from Norway rats and implanted into Lewis rats, bridging the C5 to T1 nerve
Dental caries and externalizing behaviour problems in a high‐risk child population

The aim of this study was to assess the association between externalizing behaviour problems and dental caries in children. A further objective was to explore direct and indirect pathways between sociodemographic factors, family functioning and parenting factors, oral health behaviours, externalizing behaviour problems, and dental caries using structural equation modelling. Cross‐sectional data were collected on 251, 5‐ to 8‐yr‐old children from a paediatric dental practice in the Netherlands. Children's decayed, missing, and filled primary teeth (dmft) scores were obtained from their dental records. Validated self‐report questionnaires were used to collect sociodemographic, behavioural, and family‐related data. Externalizing problem behaviour was significantly associated with a higher dmft score [incidence risk ratio (IRR) = 1.19; 95% CI: 1.06–1.34], but this association did not remain significant after adjustment for sociodemographic factors (IRR = 1.11; 95% CI: 0.99–1.26). A valid path model was presented after applying some modifications. Findings from the model suggest that it is plausible that child behaviour problems are directly associated with dental caries via toothbrushing behaviour. The model also provided support that maternal education level, the restrictiveness and warmth of parenting, and the communication of the family, play an indirect role in the association between children's externalizing behavioural problems and dental caries experience.
Protein Intake at Breakfast Promotes a Positive Whole-Body Protein Balance in a Dose-Response Manner in Healthy Children: A Randomized Trial.

Background Protein ingestion promotes whole-body net protein balance (NB) in children, which is a prerequisite for growth. Determining how much protein is required at breakfast to promote a positive NB, which may be negative after the traditional overnight fast in children, has yet to be determined. Objective We determined the impact of incremental doses of milk protein at breakfast as well as the impact of daily dietary protein distribution on NB in children. Methods A total of 28 children [14 boys, 14 girls; age range: 7-11 y; body mass index (mean ± SD, in kg/m2): 16.0 ± 1.9] completed 2 intervention trials. During the breakfast meal, participants consumed an isoenergetic beverage with different amounts of protein (0, 7, 14, or 21 g for Groups A-D, respectively) and [15N]-glycine to measure whole body protein metabolism. Whole-body nitrogen turnover, protein synthesis (PS), protein breakdown, and NB were measured over 9 and 24 h. Results Following an overnight fast, children were in negative NB (-64.5 mg · kg-1 · h-1). Protein ingestion at breakfast induced a stepwise increase in NB over 9 h [Groups A (6.2 mg · kg-1 · h-1) < B (27.9 mg · kg-1 · h-1) < C (46.9 mg · kg-1 · h-1) < D (66.0 mg · kg-1 · h-1)] with all conditions different from each other (all P < 0.01). PS was 42% greater in Group D than in Group A over 9 h (P < 0.05). Conclusions Consuming ≥7 g of the total daily protein intake at breakfast attenuates the observed overnight protein losses in children during the subsequent 9 h following breakfast consumption. The dose-dependent increase in NB over a daytime fed period, inclusive of breakfast and lunch, highlights the importance of breakfast protein intake on acute anabolism in healthy active children. This trial was registered at clinicaltrials.gov as NCT02465151.