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Background & aimsPathologists quantify liver steatosis as the fraction of lipid droplet-containing hepatocytes out of all hepatocytes, whereas the magnetic resonance-determined proton density fat fraction (PDFF) reflects the tissue triacylglycerol concentration. We investigated the linearity, agreement, and correspondence thresholds between histological steatosis and PDFF across the full clinical spectrum of liver fat content associated with non-alcoholic fatty liver disease.MethodsUsing individual patient-level measurements, we conducted a systematic review and meta-analysis of studies comparing histological steatosis with PDFF determined by magnetic resonance spectroscopy or imaging in adults with suspected non-alcoholic fatty liver disease. Linearity was assessed by meta-analysis of correlation coefficients and by linear mixed modelling of pooled data, agreement by Bland-Altman analysis, and thresholds by receiver operating characteristic analysis. To explain observed differences between the methods, we used RNA-seq to determine the fraction of hepatocytes in human liver biopsies.ResultsEligible studies numbered 9 (N = 597). The relationship between PDFF and histology was predominantly linear (r = 0.85 [95% CI, 0.80-0.89]), and their values approximately coincided at 5% steatosis. Above 5% and towards higher levels of steatosis, absolute values of the methods diverged markedly, with histology exceeding PDFF by up to 3.4-fold. On average, 100% histological steatosis corresponded to a PDFF of 33.0% (29.5-36.7%). Targeting at a specificity of 90%, optimal PDFF thresholds to predict histological steatosis grades were ≥5.75% for ≥S1, ≥15.50% for ≥S2, and ≥21.35% for S3. Hepatocytes comprised 58 ± 5% of liver cells, which may partly explain the lower values of PDFF vs. histology.ConclusionsHistological steatosis and PDFF have non-perfect linearity and fundamentally different scales of measurement. Liver fat values obtained using these methods may be rendered comparable by conversion equations or threshold values.Impact and implicationsMagnetic resonance-proton density fat fraction (PDFF) is increasingly being used to measure liver fat in place of the invasive liver biopsy. Understanding the relationship between PDFF and histological steatosis fraction is important for preventing misjudgement of clinical status or treatment effects in patient care. Our analysis revealed that histological steatosis fraction is often significantly higher than PDFF, and their association varies across the spectrum of fatty liver severity. These findings are particularly important for physicians and clinical researchers, who may use these data to interpret PDFF measurements in the context of histologically evaluated liver fat content.

Abstract We analyze the chiral separation effect (CSE) in QCD by using the gauge/gravity duality. In QCD, this effect arises from a combination of chiral anomalies and the axial U(1) anomaly. Due to the axial gluon anomaly, the value of the CSE conductivity is not determined by the anomalies of QCD but receives radiative corrections, which leads to nontrivial dependence on temperature and density. To analyze this dependence, we use different variants of the V-QCD, a complex holographic model, carefully fitted to QCD data. We find our results for the anomalous CSE conductivity at small chemical potential and nonzero temperature to be in good qualitative agreement with recent results from lattice QCD simulations. We furthermore give predictions for the behavior of the conductivity at finite (vectorial and axial) chemical potentials.

Background:. The Finnish Shaft of the Humerus (FISH) trial compared open reduction and internal plate fixation (ORIF) with functional bracing in adult patients with displaced, closed humeral shaft fractures. Here, we compare the results of the patients in the randomized clinical trial (RCT [the randomized cohort]) with those of the cohort of patients who were also eligible but declined randomization (the nonrandomized cohort) to investigate if patients’ treatment preference was associated with the outcomes during a 2-year follow-up. Methods:. A total of 321 patients were treated at 2 university hospitals in Finland between November 2012 and January 2018. Of the 140 eligible patients, 82 were randomized to ORIF or functional bracing. Of the 58 patients declining randomization, 42 consented to participate in a nonrandomized cohort in which the patients were able to choose the treatment method. The primary outcome of this study was the Disabilities of the Arm, Shoulder and Hand (DASH) score. Patients in the randomized cohort and the nonrandomized cohort were analyzed separately in 3 groups: those who had (1) initial surgery, (2) successful functional bracing, and (3) late surgery due to failed functional bracing. We used mixed-model, repeated-measures analysis of variance to compare the treatment effect among the 3 groups. Results:. In the randomized cohort, 38 patients had an initial surgical procedure. Of the 44 patients randomized to functional bracing, 30 (68%) healed successfully and 14 (32%) underwent a late surgical procedure. In the nonrandomized cohort, 9 patients preferred an initial surgical procedure. Of the 33 patients preferring functional bracing, 26 (79%) healed successfully and 7 (21%) underwent late surgery. The DASH scores in the randomized cohort and the nonrandomized cohort were 6.8 (95% confidence interval [CI], 2.3 to 11.4) and 12.3 (95% CI, 0.3 to 24.3) for the initial surgery groups, 6.0 (95% CI, 1.0 to 11.0) and 3.4 (95% CI, 0 to 9.3) for the bracing groups, and 17.5 (95% CI, 10.5 to 24.5) and 20.5 (95% CI, 9.4 to 31.6) for the late surgery groups at 2 years. Conclusions:. The results of the randomized cohort and the nonrandomized cohort were comparable and suggest that patients’ treatment preferences are not associated with the treatment outcomes of these injuries. Level of Evidence:. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Objectives: To investigate the cost-effectiveness of protein-rich meals and snacks for increasing protein intake in home-dwelling older adults. Design: Cost effectiveness analysis from a randomized controlled trial, the Power Meals study. Setting: Participants were randomized into one of three groups for eight weeks: a protein-rich meal, snack and bread (Protein), a regular meal (Normal) and a control group without meal service (Control). Participants: Home-dwelling home care clients, caregivers and care recipients aged ≥65 years (n = 65). Measurements: Protein intake was assessed by a three-day food diary at the end of the study. Cost for the daily diet was estimated by using Finnish grocery store databases and the prices of the food service. The cost-effectiveness was assessed by an incremental cost-effectiveness ratio (ICER). Results: Costs for the daily diet in the Protein (8.35 €/d) and the Normal (7.94 €/d) groups were significantly higher than in the control group (5.65 €/d) (p

BackgroundPervasive technologies are used to investigate various phenomena outside the laboratory setting, providing valuable insights into real-world human behavior and interaction with the environment. However, conducting longitudinal field trials in natural settings remains challenging due to factors such as low recruitment success and high dropout rates due to participation burden or data quality issues with wireless sensing in changing environments. ObjectiveThis study gathers insights and lessons from 3 real-world longitudinal field studies assessing human behavior and derives factors that impacted their research success. We aim to categorize challenges, observe how they were managed, and offer recommendations for designing and conducting studies involving human participants and pervasive technology in natural settings. MethodsWe developed a qualitative coding framework to categorize and address the unique challenges encountered in real-life studies related to influential factor identification, stakeholder management, data harvesting and management, and analysis and interpretation. We applied inductive reasoning to identify issues and related mitigation actions in 3 separate field studies carried out between 2018 and 2022. These 3 field studies relied on gathering annotated sensor data. The topics involved stress and environmental assessment in an office and a school, collecting self-reports and wrist device and environmental sensor data from 27 participants for 3.5 to 7 months; work activity recognition at a construction site, collecting observations and wearable sensor data from 15 participants for 3 months; and stress recognition in location-independent knowledge work, collecting self-reports and computer use data from 57 participants for 2 to 5 months. Our key extension for the coding framework used a stakeholder identification method to identify the type and role of the involved stakeholder groups, evaluating the nature and degree of their involvement and influence on the field trial success. ResultsOur analysis identifies 17 key lessons related to planning, implementing, and managing a longitudinal, sensor-based field study on human behavior. The findings highlight the importance of recognizing different stakeholder groups, including those not directly involved but whose areas of responsibility are impacted by the study and therefore have the power to influence it. In general, customizing communication strategies to engage stakeholders on their terms and addressing their concerns and expectations is essential, while planning for dropouts, offering incentives for participants, conducting field tests to identify problems, and using tools for quality assurance are relevant for successful outcomes. ConclusionsOur findings suggest that field trial implementation should include additional effort to clarify the expectations of stakeholders and to communicate with them throughout the process. Our framework provides a structured approach that can be adopted by other researchers in the field, facilitating robust and comparable studies across different contexts. Constantly managing the possible challenges will lead to better success in longitudinal field trials and developing future technology-based solutions.

Human milk contains all of the essential nutrients required by the infant within a complex matrix that enhances the bioavailability of many of those nutrients. In addition, human milk is a source of bioactive components, living cells and microbes that facilitate the transition to life outside the womb. Our ability to fully appreciate the importance of this matrix relies on the recognition of short- and long-term health benefits and, as highlighted in previous sections of this supplement, its ecology (i.e., interactions among the lactating parent and breastfed infant as well as within the context of the human milk matrix itself). Designing and interpreting studies to address this complexity depends on the availability of new tools and technologies that account for such complexity. Past efforts have often compared human milk to infant formula, which has provided some insight into the bioactivity of human milk, as a whole, or of individual milk components supplemented with formula. However, this experimental approach cannot capture the contributions of the individual components to the human milk ecology, the interaction between these components within the human milk matrix, or the significance of the matrix itself to enhance human milk bioactivity on outcomes of interest. This paper presents approaches to explore human milk as a biological system and the functional implications of that system and its components. Specifically, we discuss study design and data collection considerations and how emerging analytical technologies, bioinformatics, and systems biology approaches could be applied to advance our understanding of this critical aspect of human biology.

Abstract Background Upper tract urothelial carcinoma (UTUC) is a rare malignancy, with typically only few new cases annually per urological department. Adherence to European association of urology (EAU) guidelines on UTUC in the Nordic countries is unknown. The objective of this survey was to examine the implementation of EAU guidelines, the perioperative management and organization of the treatment of UTUC in the Nordic countries. Methods The electronic survey was distributed to 93 hospitals in the Nordic countries performing radical nephroureterectomy (NU). The survey consisted of 57 main questions and data was collected between December 1st, 2021 and April 23rd, 2022. Results Overall response rate was 47/93 (67%) with a completion rate of 98%. Five out of the 6 examined subjects on diagnostic practice are applied by ≥ 72% of the participating centers. NU as treatment for high-risk UTUC is performed by 37/47 (79%), and 91% include a bladder cuff excision. Conclusions Adherence to EAU guidelines is high on diagnostic practice in the Nordic countries, whereas disease management is less coherent.

Abstract Human milk (HM) components affect immune cell toll-like receptor 4 (TLR4) signaling. However, studies examining the immunomodulatory impacts of HM on TLR4 signaling in intestinal epithelial cells (IECs) are limited. This study utilized both a TLR4 reporter cell line and a Caco-2 IEC model to examine the effects of HM on lipopolysaccharide (LPS)-induced TLR4 activation and cytokine responses, respectively. Additionally, we performed fast protein liquid chromatography and mass spectrometry to identify a HM component that contributes to the effect of HM on LPS/TLR4 signaling. HM enhances LPS-induced TLR4 signaling as well as LPS-induced IEC gene expression of pro-inflammatory cytokines and negative regulators of NF-κB. Human serum albumin (HSA) present in HM contributes to these effects. HSA within HM synergizes with LPS to induce IEC gene expression of pro-inflammatory cytokines and negative regulators of NF-κB. Altogether, this study provides mechanistic evidence behind the immunomodulatory function of HM on IECs, which may contribute to an enhanced immune response in breast-fed neonates.

IntroductionIn this prospective cohort study over 40 years we investigated the effect of childhood attention-deficit/hyperactivity disorder (ADHD) and subthreshold ADHD on cognitive performance in adulthood.MethodsThe cohort comprised individuals with mild perinatal risks. Childhood ADHD group (cADHD, n = 39) was compared to a group with subthreshold childhood attention or hyperactivity symptoms (cAP; n = 79), a group with similar perinatal risks but no ADHD symptoms (n = 255), and to controls without ADHD symptoms or perinatal risks (n = 69). The groups were assessed with multiple neuropsychological measures in domains of verbal reasoning, perceptual skills, memory, working memory, attention, executive functions, and speed. Group-level differences and frequencies of deficient functioning were analyzed.ResultsOverall, the groups’ performance differed in all cognitive domains at age 40. Verbal reasoning, perceptual skills, memory, and speed had the largest effect sizes (0.51–0.62). The cADHD group’s performance was lower than the other groups’ on 13 out of 21 measures. The cAP group performed poorer than controls on five measures. In the cADHD group, 23% had three or more deficient cognitive domains, compared to 4–6% in the other groups.DiscussionChildhood ADHD is associated with impaired cognitive functioning in adulthood on several cognitive domains whereas childhood subthreshold ADHD is linked to fewer cognitive deficits. Task complexity was linked to poorer performance within the ADHD group. Our results add to the scarce longitudinal evidence of cognitive outcomes related to childhood ADHD and subthreshold symptoms.

Given the gradual nature of the energy transition, retrofitting coal-fired power plants with carbon capture technology is crucial. The calcium looping (CaL) process is a promising solution, with challenges like absorbent deactivation and reduced thermal efficiency mitigated by absorbent reactivation and heat recovery systems. This study evaluated the techno-economic feasibility of integrating a novel wet extraction and precipitation process for absorbent reactivation within a solar-assisted CaL system, alongside an existing coal power plant. The process incorporated a secondary steam cycle and an ammonia absorption chiller for enhanced heat recovery and district cooling. The integrated project could increase daily power generation by 50% and reduce CO2 emissions from 820.4 g/kWh to 54.5 g/kWh. Over its lifespan, the reactivation facility could reduce limestone extraction by 21 Mt with 90% capture efficiency. With a levelized cost of electricity (LCOE) of 116.1 €/MWh and breakeven electricity selling price (BESP) of 56.6 €/MWh, the system demonstrated promising commercial viability, with the reactor and concentrated solar heating (CSH) system making up over 60% of investment costs. CSH cost and solar abundance were identified as key factors, indicating potential feasibility even in higher latitude regions. At CO2 revenues of 150 €/t, a stand-alone capture project can break even based solely on CO2 sales, demonstrating its potential for expansion to other areas. A case study highlighted the benefits of integrating absorbent reactivation and an ammonia absorption chiller, improving both economics and carbon capture efficiency. The study also confirmed the viability of solar-assisted projects in high-latitude regions, with optimistic future CO2 revenues and advancements in carbon capture technology enhancing feasibility.

BACKGROUNDA pilot, single-center study showed that first-degree relatives of probands with nonalcoholic fatty liver disease (NAFLD) cirrhosis have a high risk of advanced fibrosis. We aimed to validate these findings using 2 independent cohorts from the US and Europe.METHODSThis prospective study included probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD, with at least 1 first-degree relative. A total of 396 first-degree relatives - 220 in a derivation cohort and 176 in a validation cohort - were enrolled in the study, and liver fibrosis was evaluated using magnetic resonance elastography and other noninvasive imaging modalities. The primary outcome was prevalence of advanced fibrosis in first-degree relatives.RESULTSPrevalence of advanced fibrosis in first-degree relatives of probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD was 15.6%, 5.9%, and 1.3%, respectively (P = 0.002), in the derivation cohort, and 14.0%, 2.6%, and 1.3%, respectively (P = 0.004), in the validation cohort. In multivariable-adjusted logistic regression models, age of ≥50 years (adjusted OR [aOR]: 2.63, 95% CI 1.0-6.7), male sex (aOR: 3.79, 95% CI 1.6-9.2), diabetes mellitus (aOR: 3.37, 95% CI 1.3-9), and a first-degree relative with NAFLD with advanced fibrosis (aOR: 11.8, 95% CI 2.5-57) were significant predictors of presence of advanced fibrosis (all P < 0.05).CONCLUSIONFirst-degree relatives of probands with NAFLD with advanced fibrosis have significantly increased risk of advanced fibrosis. Routine screening should be done in the first-degree relatives of patients with advanced fibrosis.FUNDINGSupported by NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515, K23DK119460), NHLBI (P01HL147835), and NIAAA (U01AA029019); Academy of Finland grant 309263; the Novo Nordisk, EVO, and Sigrid Jusélius Foundations; and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 777377. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and the EFPIA.