Miracle-dz/UniFAR-FTUs huggingface dataset:
More or less energy with age? A motivational life-span perspective on subjective energy, exhaustion, and opportunity costs.

Two studies investigated subjective conceptualizations of energy for goal pursuit across adulthood. Study 1 (N = 276, 20-92 years of age) explored age-related differences in the (a) endorsement of a limited versus nonlimited account of energy for goal pursuit, (b) amount of energy available for physically, mentally, socially, and emotionally demanding activities, and (c) extent to which spending energy on a demanding activity inhibits or facilitates energy expenditure for subsequent activities, both within and across functional domains. Study 2 (N = 147, 18-86 years of age) experimentally induced energy loss through a 20-min physical exercise and examined age-related differences in the increase of subjective exhaustion and opportunity costs as a motivational cue for goal disengagement. With increasing age, adults more strongly endorsed a nonlimited account of energy and perceived having more energy available for personally relevant social activities. However, older adults also reported higher negative cross-domain energy spillover after physical exertion. Multilevel growth curve models further revealed that, compared with younger adults, older adults reported a steeper initial increase in exhaustion and opportunity costs during physical exercise, but converged with the younger age groups again at the close of the exercise session. The discussion centers around the importance of selectivity in older adulthood and motivational accounts of effort and exhaustion. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
The future of autoimmune liver diseases – Understanding pathogenesis and improving morbidity and mortality

Autoimmune liver diseases (AILD), namely autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are rare diseases. These days, patients with PBC almost never require liver transplantation. When treated early with ursodeoxycholic acid patients have a normal life expectancy if the disease is diagnosed at an early stage and the patients respond to treatment. Patients with AIH often go into remission with first‐line therapy including corticosteroids alone or in combination with azathioprine. Nevertheless, about one quarter of patients already developed cirrhosis at diagnosis. Those who do not respond to first line standard of care (SOC) have significant liver‐related morbidity and mortality. No approved second‐ or third‐line treatments are available and the drugs are selected based on limited case series and personal experience. Larger trials are needed to develop efficient therapies for difficult‐to‐treat AIH patients. No treatment has been found to alter the natural course of disease in patients with PSC except for liver transplantation. Identifying PSC patients at risk of developing cholangiocarcinoma (CCA) is another unmet need. Current research in all AILD including AIH, PBC and PSC, focuses on improving our understanding of the underlying disease process and identifying new therapeutic targets to decrease morbidity and mortality.
Long‐term serial functional evaluation after implantation of the Fantom sirolimus‐eluting bioresorbable coronary scaffold

Quantitative flow ratio (QFR) has been validated as an accurate surrogate of standard wire‐based fractional flow reserve. The clinical and angiographic outcomes of the Fantom sirolimus‐eluting bioresorbable coronary scaffold (BRS) have been previously studied and reported. We investigate the functional performance of the Fantom BRS.
Automated Myocardial T2 and Extracellular Volume Quantification in Cardiac MRI Using Transfer Learning-based Myocardium Segmentation.

Purpose To assess the performance of an automated myocardial T2 and extracellular volume (ECV) quantification method using transfer learning of a fully convolutional neural network (CNN) pretrained to segment the myocardium on T1 mapping images. Materials and Methods A single CNN previously trained and tested using 11 550 manually segmented native T1-weighted images was used to segment the myocardium for automated myocardial T2 and ECV quantification. Reference measurements from 1525 manually processed T2 maps and 1525 ECV maps (from 305 patients) were used to evaluate the performance of the pretrained network. Correlation coefficient (R) and Bland-Altman analysis were used to assess agreement between automated and reference values on per-patient, per-slice, and per-segment analyses. Furthermore, transfer learning effectiveness in the CNN was evaluated by comparing its performance to four CNNs trained using manually segmented T2-weighted and postcontrast T1-weighted images and initialized using random-weights or weights of the pretrained CNN. Results T2 and ECV measurements using the pretrained CNN strongly correlated with reference values in per-patient (T2: R = 0.88, 95% confidence interval [CI]: 0.85, 0.91; ECV: R = 0.91, 95% CI: 0.89, 0.93), per-slice (T2: R = 0.83, 95% CI: 0.81, 0.85; ECV: R = 0.84, 95% CI: 0.82, 0.86), and per-segment (T2: R = 0.75, 95% CI: 0.74, 0.77; ECV: R = 0.76, 95% CI: 0.75, 0.77) analyses. In Bland-Altman analysis, the automatic and reference values were in good agreement in per-patient (T2: 0.3 msec ± 2.9; ECV: -0.3% ± 1.7), per-slice (T2: 0.1 msec ± 4.6; ECV: -0.3% ± 2.5), and per-segment (T2: 0.0 msec ± 6.5; ECV: -0.4% ± 3.5) analyses. The performance of the pretrained network was comparable to networks refined or trained from scratch using additional manually segmented images. Conclusion Transfer learning extends the utility of pretrained CNN-based automated native T1 mapping analysis to T2 and ECV mapping without compromising performance. Supplemental material is available for this article. © RSNA, 2020.
Risk Factors for Mortality among Patients with Pseudomonas aeruginosa Bloodstream Infections: What Is the Influence of XDR Phenotype on Outcomes?

This study aimed to assess the impact of extensively drug-resistant (XDR) phenotype on mortality in Pseudomonas aeruginosa bacteremia. A retrospective cohort study was performed in a tertiary hospital from January 2000 to December 2018. All consecutive prospectively recorded P. aeruginosa bacteremia in adult patients were assessed. In this study, 382 patients were included, of which 122 (31.9%) due to XDR P. aeruginosa. Independent factors associated with 14-day mortality were as follows: high-risk source of bacteremia (hazard ratio (HR) 3.07, 95% confidence interval (CI), 1.73–5.46), septic shock (HR 1.75, 95% CI, 1.12–2.75), and higher Pitt scores (one-point increments; HR 1.25, 95% CI, 1.12–1.38). Otherwise, the appropriateness of definitive antibiotic therapy was a protective factor (HR 0.39, 95% CI, 0.24–0.62). The same variables were also associated with 30-day mortality. XDR phenotype was not associated with 14- or 30-day mortality. In a subanalysis considering only high-risk source cases, combined antimicrobial therapy was independently associated with 14-day favorable outcome (HR 0.56, 95% CI, 0.33–0.93). In conclusion, XDR phenotype was not associated with poor prognosis in patients with P. aeruginosa bacteremia in our cohort. However, source of infection, clinical severity, and inappropriate definitive antibiotic therapy were risk factors for mortality. Combined antimicrobial therapy should be considered for high-risk sources.
Novel Biomarkers for Evaluation of Endothelial Dysfunction

Endothelial dysfunction is one of the earliest indicators of cardiovascular (CV) dysfunction, and its evaluation would be of considerable importance to stratify CV risk of many diseases and to assess the efficacy of atheroprotective treatments. Flow-mediated dilation is the most widely used method to study endothelial function. However, it is operator-dependent and can be influenced by physiological variations. Circulating biomarkers are a promising alternative. Due to the complexity of endothelial function, many of the biomarkers studied do not provide consistent information about the endothelium when measured alone. New circulating markers are being explored and some of them are thought to be suitable for the clinical setting. In this review, we focus on novel biomarkers of endothelial dysfunction, particularly endothelial microparticles, endocan, and endoglin, and discuss whether they fulfill the criteria to be applied in clinical practice.
Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2–mediated activation of forkhead box O1

Recent clinical investigations indicate that anthracycline-based chemotherapies induce early decline in heart mass in cancer patients. Heart mass decline may be caused by a decrease in cardiac cell number because of increased cell death or by a reduction in cell size because of atrophy. We previously reported that an anthracycline, doxorubicin (DOX), induces apoptotic death of cardiomyocytes by activating cyclin-dependent kinase 2 (CDK2). However, the signaling pathway downstream of CDK2 remains to be characterized, and it is also unclear whether the same pathway mediates cardiac atrophy. Here we demonstrate that DOX exposure induces CDK2-dependent phosphorylation of the transcription factor forkhead box O1 (FOXO1) at Ser-249, leading to transcription of its proapoptotic target gene, Bcl-2–interacting mediator of cell death (Bim). In cultured cardiomyocytes, treatment with the FOXO1 inhibitor AS1842856 or transfection with FOXO1-specific siRNAs protected against DOX-induced apoptosis and mitochondrial damage. Oral administration of AS1842856 in mice abrogated apoptosis and prevented DOX-induced cardiac dysfunction. Intriguingly, pharmacological FOXO1 inhibition also attenuated DOX-induced cardiac atrophy, likely because of repression of muscle RING finger 1 (MuRF1), a proatrophic FOXO1 target gene. In conclusion, DOX exposure induces CDK2-dependent FOXO1 activation, resulting in cardiomyocyte apoptosis and atrophy. Our results identify FOXO1 as a promising drug target for managing DOX-induced cardiotoxicity. We propose that FOXO1 inhibitors may have potential as cardioprotective therapeutic agents during cancer chemotherapy.
Postpartum Involution and Cancer: An Opportunity for Targeted Breast Cancer Prevention and Treatments?

Childbirth at any age confers a transient increased risk for breast cancer in the first decade postpartum and this window of adverse effect extends over two decades in women with late-age first childbirth (>35 years of age). Crossover to the protective effect of pregnancy is dependent on age at first pregnancy, with young mothers receiving the most benefit. Furthermore, breast cancer diagnosis during the 5- to 10-year postpartum window associates with high risk for subsequent metastatic disease. Notably, lactation has been shown to be protective against breast cancer incidence overall, with varying degrees of protection by race, multiparity, and lifetime duration of lactation. An effect for lactation on breast cancer outcome after diagnosis has not been described. We discuss the most recent data and mechanistic insights underlying these epidemiologic findings. Postpartum involution of the breast has been identified as a key mediator of the increased risk for metastasis in women diagnosed within 5–10 years of a completed pregnancy. During breast involution, immune avoidance, increased lymphatic network, extracellular matrix remodeling, and increased seeding to the liver and lymph node work as interconnected pathways, leading to the adverse effect of a postpartum diagnosis. We al discuss a novel mechanism underlying the protective effect of breastfeeding. Collectively, these mechanistic insights offer potential therapeutic avenues for the prevention and/or improved treatment of postpartum breast cancer.
A Novel Micronutrient Blend Mimics Calorie Restriction Transcriptomics in Multiple Tissues of Mice and Increases Lifespan and Mobility in C. elegans

Background: We previously described a novel micronutrient blend that behaves like a putative calorie restriction mimetic. The aim of this paper was to analyze the beneficial effects of our micronutrient blend in mice and C. elegans, and compare them with calorie restriction. Methods: Whole transcriptomic analysis was performed in the brain cortex, skeletal muscle and heart in three groups of mice: old controls (30 months), old + calorie restriction and old + novel micronutrient blend. Longevity and vitality were tested in C. elegans. Results: The micronutrient blend elicited transcriptomic changes in a manner similar to those in the calorie-restricted group and different from those in the control group. Subgroup analysis revealed that nuclear hormone receptor, proteasome complex and angiotensinogen genes, all of which are known to be directly related to aging, were the most affected. Furthermore, a functional analysis in C. elegans was used. We found that feeding C. elegans the micronutrient blend increased longevity as well as vitality. Conclusions: We describe a micronutrient supplement that causes similar changes (transcriptomic and promoting longevity and vitality) as a calorie restriction in mice and C. elegans, respectively, but further studies are required to confirm these effects in humans.
Fair enough? Decreased equity of dyadic coping across the transition to parenthood associated with depression of first-time parents

The transition to parenthood (TTP) is a stressful life event for most couples. Therefore, the way both partners jointly cope with stress (i.e., dyadic coping) is important for the prevention of individual adjustment problems (e.g., depression). For dyadic coping to be effective in reducing depressive symptoms, efforts of both partners should be equal. However, many couples experience a decrease of equity in task division within the domestic sphere across the TTP. The current study investigates the equity of a specific skill within the ‘relationship sphere’, because similarly to a decreased equity in household and childcare, a decreased equity of dyadic coping is likely to be associated with poorer individual adjustment. We collected longitudinal self-report data on dyadic coping and depressive symptoms from 104 mixed-gender first-time parents (n = 208 individuals) from pregnancy until 40 weeks postpartum. We created an equity score for men and women that measured their perceived difference between received and provided dyadic coping. On average, women reported providing more and receiving less dyadic coping than men. While both genders agreed on this distribution, men did perceive a higher equity of dyadic coping than women. Furthermore, the decrease of equity perceived by women across TTP was not visible in men. In line with our assumptions based on the equity theory, perceived equity of dyadic coping was associated with depressive symptoms in a curvilinear manner: Decreases in women’s perceived equity in either direction (over- or underbenefit) were associated with more depressive symptoms in women and their male partners. This association was found above and beyond the beneficial effect of dyadic coping itself. This implies that not only how well partners support each other in times of stress, but also how equal both partners’ efforts are, is important for their individual adjustment across TTP.
Intentions to Seek Information About the Influenza Vaccine: The Role of Informational Subjective Norms, Anticipated and Experienced Affect, and Information Insufficiency Among Vaccinated and Unvaccinated People

When deciding whether to vaccinate, people often seek information through consequential processes that are not currently well understood. A survey of a nationally representative sample of U.S. adults (N = 2,091) explored the factors associated with intentions to seek influenza vaccine information in the 2018–2019 influenza season. This survey shed light on what motivates intentions to seek information about the influenza vaccine through the lens of the risk information seeking and processing (RISP) model. The model explained information‐seeking intentions well among both unvaccinated and vaccinated respondents. Key findings show that informational subjective norms, information insufficiency, and different types of affect are strong predictors of information‐seeking intentions. Theoretical insights on extending the RISP model and practical guidance on designing interventions are provided.
Diaporthe species associated with twig blight and dieback of Vaccinium corymbosum in Portugal, with description of four new species

ABSTRACT Blueberry, an increasingly cultivated fruit crop in Portugal, is known to be susceptible to twig blight and dieback caused by species of Diaporthe. The diversity of Diaporthe species associated with symptomatic and asymptomatic Vaccinium corymbosum plants in Portugal was assessed. A multilocus sequence analysis of the rDNA internal transcribed spacer (ITS) region and the translation elongation factor 1-alpha (tef1-α), β-tubulin (tub2), calmodulin (cal), and histone 3 (his3) genes revealed the presence of Diaporthe foeniculina, Diaporthe rudis, and four new species, which are described as Diaporthe crousii, Diaporthe phillipsii, Diaporthe rossmaniae, and Diaporthe vacuae. These new species were characterized in terms of their morphology, mating strategies, and temperature growth requirements. In artificial inoculation trials of V. corymbosum cv. Bluecrop plants, all Diaporthe species caused minor symptoms. Further, no differences in aggressiveness were apparent between species. This study provides the first survey of Diaporthe species associated with blueberry twig blight and dieback in Portugal. It disclosed the occurrence of a diverse assemblage of Diaporthe species, whose status and impact as pathogens of blueberry is not yet fully understood.
Calcium Signaling in the Oligodendrocyte Lineage: Regulators and Consequences.

Cells of the oligodendrocyte lineage express a wide range of Ca2+ channels and receptors that regulate oligodendrocyte progenitor cell (OPC) and oligodendrocyte formation and function. Here we define those key channels and receptors that regulate Ca2+ signaling and OPC development and myelination. We then discuss how the regulation of intracellular Ca2+ in turn affects OPC and oligodendrocyte biology in the healthy nervous system and under pathological conditions. Activation of Ca2+ channels and receptors in OPCs and oligodendrocytes by neurotransmitters converges on regulating intracellular Ca2+, making Ca2+ signaling a central candidate mediator of activity-driven myelination. Indeed, recent evidence indicates that localized changes in Ca2+ in oligodendrocytes can regulate the formation and remodeling of myelin sheaths and perhaps additional functions of oligodendrocytes and OPCs. Thus, decoding how OPCs and myelinating oligodendrocytes integrate and process Ca2+ signals will be important to fully understand central nervous system formation, health, and function. Expected final online publication date for the Annual Review of Neuroscience, Volume 43 is July 8, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Development and Validation of a Brief Hospital-Based Ambulatory Patient Experience Survey Tool

Recognition of the value of the patient perspective on services has led healthcare organizations to measure patient care experiences. A brief, generic and psychometrically sound scale to measure patient experiences in ambulatory/outpatient settings in Canada would be useful and is currently lacking. The purpose of this study was to develop and validate an English-language hospital-based ambulatory patient experience survey tool in a Canadian context. Based on a review of more than 20 instruments measuring experiences predominately in non-acute care settings, we initially selected 27 items to be included in the questionnaire, addressing quality dimensions of access, communication, continuity and coordination, shared decision making, emotional support, trust/confidence, privacy, patient-reported impact and physical environment. The survey instrument was subsequently tested among 1,219 ambulatory patients, and its psychometric properties were assessed. A final questionnaire was produced with 14 items and two emerging subscales: Patient–Provider Communication and Overall Quality of Experience, as determined by a factor analysis. The items within the scale showed high construct validity. Reliability was also excellent for the instrument. The applicability of this tool in supporting quality improvement initiatives is discussed.
Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients

Melatonin is a multifaceted hormone which rises upon the onset of darkness. Pineal synthesis of melatonin is known to be disturbed in patients with end-stage renal disease, but it is not known if its production is restored to normal after successful renal transplantation. We hypothesized that urinary excretion of 6-sulfatoxymelatonin, the major metabolite of melatonin, is lower in renal transplant recipients (RTRs) compared to healthy controls and that this is associated with excess mortality. Urinary 6-sulfatoxymelatonin was measured via LC-MS/MS in 701 stable outpatient RTRs and 285 healthy controls. Median urinary 6-sulfatoxymelatonin in RTR was 13.2 nmol/24 h, which was 47% lower than in healthy controls. Urinary 6-sufatoxymelatonin appeared undetectable in the majority of 36 RTRs with diabetic nephropathy as primary renal disease. Therefore, this subgroup was excluded from further analyses. Of the remaining 665 RTRs, during 5.4 years of follow-up, 110 RTRs died, of whom 38 died due to a cardiovascular cause. In Cox-regression analyses, urinary 6-sulfatoxymelatonin was significantly associated with all-cause mortality (0.60 (0.44–0.81), p = 0.001) and cardiovascular mortality (0.49 (0.29–0.84), p = 0.009), independent of conventional risk factors and kidney function parameters. Based on these results, evaluation and management of melatonin metabolism could be considered for improvement of long-term outcomes in RTRs.
Contributing mechanisms underlying desensitization of CCK-induced activation of primary nodose ganglia neurons.

Cholecystokinin (CCK) is a gut-derived peptide that potently promotes satiety and facilitates gastric function in part by activating G-protein coupled CCK1 receptors on primary vagal afferent neurons. CCK signaling is dynamic and rapidly desensitizes, due to decreases in either receptor function and the resulting signal cascade, ion channel effectors, or both. Here we report a decay-time analytical approach using fluorescent calcium imaging that relates peak and steady-state calcium responses in dissociated vagal afferent neurons, enabling discrimination between receptor and ion channel effector functions. We found desensitization of CCK induced activation was predictable, consistent across cells, and strongly concentration dependent. The decay-time constant (tau) was inversely proportional to CCK concentration, apparently reflecting the extent of receptor activation. To test this possibility, we directly manipulated the ion channel effector(s) with either decreased bath calcium or the broad-spectrum pore blocker ruthenium red. Conductance inhibition diminished the magnitude of the CCK responses without altering decay kinetics; confirming changes in tau reflect changes in receptor function selectively. Next, we investigated the contributions of the PKC and PKA signaling cascades on the magnitude and decay-time constants of CCK calcium responses. While inhibition of either PKC or PKA increased CCK calcium response magnitude, only PKC significantly decreased the decay-time constant. These findings suggest that PKC alters CCK receptor signaling dynamics, while PKA alters the ion channel effector of the CCK response. This analytical approach should prove useful in understanding receptor / effector changes underlying acute desensitization of G-protein coupled signaling and provide insight into CCK receptor dynamics.