Miracle-dz/UniFAR-FTUs huggingface dataset:
Peroxisome proliferator‐activated receptor‐α agonist and all‐trans retinoic acid induce epithelial differentiation of subcutaneous adipose‐derived stem cells from debrided burn skin

This study demonstrates that adipose‐derived stem cells from debrided skin (dsASCs) of burn patients can be isolated in sufficient quantities and differentiated into cytokeratin‐expressing cells by treating them with all‐trans retinoic acid (ATRA) and the peroxisome proliferator‐activated receptor‐α (PPARα) specific activator fenofibrate. Differentiation of dsASCs with ATRA and a combination of growth factors induced expression of simple epithelial markers (KRT7, KRT8, KRT18, and KRT19), along with low levels of stratified epithelial markers (KRT5, KRT10, KRT13, and KRT14). We have optimized a condition to induce dsASCs differentiation to epithelial cells by treatment with ATRA and fenofibrate alone. Real‐time polymerase chain reaction analysis showed a significant increase in transcript levels (>75‐fold) for basal (KRT5 and KRT14), suprabasal (KRT10), and cornified envelope markers (involucrin [IVL] and Loricrin [LOR]) with this treatment. Expression of the proteins encoded by these transcripts was confirmed by immunocytochemical analysis. Further, we show that dsASCs differentiated to a skin epithelial cell phenotype through activation of nuclear hormone receptors PPARα and RXRγ. Collectively this study shows that dsASCs can be differentiated to skin epithelial cells, without the requirement for exogenous growth factors. This differentiation protocol using dsASCs in combination with an appropriate biocompatible scaffold can be adapted to develop epithelial skin substitute for burn wound treatment.
Daily oral cyanocobalamin supplementation in Beagles with hereditary cobalamin malabsorption (Imerslund‐Gräsbeck syndrome) maintains normal clinical and cellular cobalamin status

Background Efficacy of PO cobalamin (Cbl) supplementation in dogs with hereditary Cbl malabsorption (Imerslund‐Gräsbeck syndrome, IGS) is unknown. Objectives To evaluate PO Cbl supplementation in Beagles with IGS previously treated parenterally. We hypothesized that 1 mg cyano‐Cbl daily PO would maintain clinical and metabolic remission. Animals Three client‐owned Beagles with IGS and 48 healthy control dogs. Methods Prospective study. Daily PO cyanocobalamin (cyano‐Cbl; 1 mg) supplementation was monitored for 13 (2 dogs) and 8 months (1 dog). Health status was assessed by owner observations. Methylmalonic acid (MMA)‐to‐creatinine concentrations were measured using an ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐TMS) method on urine samples collected monthly. Concurrent measurements of serum MMA concentration (n = 7; UPLC‐TMS) were available for 1 dog. Results All dogs remained in excellent health during PO supplementation. Urine MMA remained consistently low in 2 dogs (median, 2.5 mmol/mol creatinine; range, 1.2‐9; healthy dogs [n = 30], median, 2.9 mmol/mol creatinine; range, 1.3‐76.5). Urine MMA ranged from 38.9‐84.9 mmol/mol creatinine during the first 6 months in 1 dog already known to excrete comparable amounts when supplemented parenterally. Brief antibiotic treatment for an unrelated condition after 6 months resulted in low urine MMA (median, 2.8 mmol/mol creatinine; range, 1.9‐4.8) for the next 7 months. All concurrent serum MMA concentrations (median, 651 nmol/L; range, 399‐919) before and after month 6 were within the established reference interval (393‐1476 nmol/L; n = 48). Conclusions and Clinical Importance One milligram of cyano‐Cbl daily PO appears efficacious for maintaining normal clinical status and normal cellular markers of Cbl metabolism in Beagles with IGS.
Elevated levels of serum nitrite and nitrate, NOx, are associated with increased total and cardiovascular mortality in an 8‐year follow‐up study

Nitric oxide (NO) is one of the key regulators of vascular function. Abnormal NO signalling is linked to various cardiovascular diseases. We studied associations between circulating levels of NO metabolites, nitrite and nitrate (NOx) and total and cardiovascular mortality in a prospective 8‐year follow‐up cohort study in 1869 patients aged over 55 years.
Identification and characterization of a core set of ROS wave‐associated transcripts involved in the systemic acquired acclimation response of Arabidopsis to excess light

Summary Systemic acquired acclimation (SAA) plays a key role in optimizing growth and preventing damage associated with fluctuating or abrupt changes in the plant environment. To be effective, SAA has to occur at a rapid rate and depend on rapid signaling pathways that transmit signals from affected tissues to all parts of the plant. Although recent studies have identified several different rapid systemic signaling pathways that could mediate SAA, very little information is known about the extent of their involvement in mediating transcriptomic responses. Here we reveal that the systemic transcriptomic response of plants to excess light stress is extensive in its context and involves an early (2 min) and transient stage of transcript expression that includes thousands of genes. This early response is dependent on the respiratory burst oxidase homolog D protein, and the function of the reactive oxygen species (ROS) wave. We further identify a core set of transcripts associated with the ROS wave and suggest that some of these transcripts are involved in linking ROS with calcium signaling. Priming of a systemic leaf to become acclimated to a particular stress during SAA involves thousands of transcripts that display a rapid and transient expression pattern driven by the ROS wave.
Orthorexia nervosa: A behavioral complex or a psychological condition?

Background and aims Numerous studies have provided evidence for orthorexia nervosa (ON), an eating pattern characterized by an almost manic obsession for and fixation on healthy eating, to be of epidemiological relevance. However, there is scientific debate on whether it is merely a behavioral or lifestyle phenomenon as compared to a mental disorder. Aim of this cross-sectional study was to explore whether ON is of epidemiological and clinical relevance, and whether ON can be distinguished from other mental health disorders and healthy lifestyle features. Methods An online survey including a measure of orthorexic behaviors [Duesseldorf Orthorexia Scale (DOS)], well-being and distress, eating behaviors, pathological eating, anxiety and depression, addictive behaviors, obsessive–compulsive symptoms, personality, and health behaviors was completed by 713 subjects (79.8% women, 18–75 years, median age: 25 years). Results Twenty-seven subjects (3.8%, 21 women) showed significant orthorexic eating (DOS ≥ 30). ON cases reported lower well-being, lower satisfaction with life, and higher current stress levels than non-ON cases. The highest percentage of variation in ON was explained by pathological eating (R2 = .380), followed by eating style, Mediterranean diet, compulsive symptoms, and subjective social status. Importantly, ON provided hardly any additional predictive value for well-being when also considering pathological eating. Discussion and conclusions Our data confirmed the epidemiological and clinical relevance of orthorexic behaviors, but the strong conceptual overlap with other mental health problems and pathological eating raise initial doubts as to whether ON is a distinct mental health disorder category. This co-occurrence, unique symptoms, and underlying processes need further exploration by comparing ON cases with patients with other mental disorders.
Enlarged and highly repetitive plastome of Lagarostrobos and plastid phylogenomics of Podocarpaceae

Podocarpaceae is the largest family in cupressophytes (conifers II), but their plastid genomes (plastomes) are poorly studied, with plastome data currently existing for only four of the 19 Podocarpaceous genera. In this study, we assembled the plastomes from representatives of eight additional genera, including Afrocarpus, Dacrydium, Lagarostrobos, Lepidothamnus, Microstrobos, Phyllocladus, Prumnopitys, and Saxegothaea. We found that Lagarostrobos, a monotypic genus native to Tasmania, has the largest plastome among any cupressophytes studied to date (151,496 bp). Plastome enlargement in Lagarostrobos coincides with increased intergenic spacers, repeats, and duplicated genes. Among Podocarpaceae, Lagarostrobos has the most rearranged plastome, but its substitution rates are modest. Plastid phylogenomic analyses clarify the positions of previously conflicting Podocarpaceous genera. Tree topologies firmly support the division of Podocarpaceae into two sister clades: (1) the Prumnopityoid clade and (2) the clade containing Podocarpoid, Dacrydioid, Microstrobos, and Saxegothaea. The Phyllocladus is nested within the Podocarpaceae, thus familial status of the monotypic Phyllocladaceae is not supported.
Long-term effectiveness and safety of canakinumab in pediatric familial Mediterranean fever patients

Abstract Background: Little is known about the long-term efficacy and safety of canakinumab in paediatric FMF patients. Aim: To present the single centre experience of colchicine-resistant paediatric-onset FMF patients who were treated with canakinumab by off-label use since 2012. Methods: The hospital files of 15 children who used canakinumab were retrospectively evaluated. Clinical and laboratory data of each visit were recorded. Drug-related adverse events were recorded. Complete remission was described as no attacks and normal acute phase reactants; partial remission was defined as decrease in severity and rate of attacks and/or elevated acute phase reactants with anti-IL-1 treatment. Results: The average duration of canakinumab use was 23.9 months (min:12, max:58 months). Twelve patients were M694V homozygotes. Eleven patients achieved complete remission after the first dose at 2 months and 12 patients at 6 months. Canakinumab interval was shortened in 2 patients from 150 mg/8 weeks to 150 mg/4 weeks. Except one, 14 patients achieved complete remission by 12 months. Two patients had mild urinary tract infections. One patient had bronchopneumonia requiring hospitalization. Two patients had teeth abscess. There were no serious adverse events such as opportunistic infections, malignancies, or deaths. Besides, no significant laboratory abnormalities occurred in complete blood count parameters, liver and kidney function tests. Conclusion: To the best of our knowledge, this is the longest outcome study about canakinumab use in paediatric FMF patients. This study suggested that canakinumab is safe and effective in children with FMF in the long term.
A scoping review to determine themes that represent perceptions of self as mother (‘ideal mother’ vs ‘real mother’)

ABSTRACT Background: Postnatal depression (PND) is a key cause of maternal morbidity, with current systems of initial recognition in the UK detecting only 50% of cases. In attempts to predict those potentially at risk, this review suggests a novel approach. Aim: Implementing the concept of ‘ideal mother’ versus ‘real mother’, and asking the woman to compare their ‘ideal self’ against ‘existent self’, the aim of this instrument development review was to determine themes from the literature that relate to women’s perceptions of self as a mother, and from this identification develop questions for inclusion within a proposed new measure entitled the Self-Image as Mother Scale (SIMS). Method: A scoping review of the literature was carried out to identify themes considered to affect perception of self as mother, and from this identification, evidence-based questions for inclusion in the SIMS were developed. Findings: Themes identified included (1) marital dissatisfaction, (2) inadequate partner support, (3) lack of family support, (4) socioeconomic status and associated poverty, (5) concern about infant, (6) antenatal/postnatal complications, (7) acceptance of infant gender, (8) history of mental health problems, (9) unplanned pregnancy. Conclusions: From this scoping review 18 questions were developed for inclusion in the SIMS, which will then be evaluated for psychometric properties, scale refinement and validation.
Phenological mismatch drives selection on elevation, but not on slope, of breeding time plasticity in a wild songbird

Phenotypic plasticity is an important mechanism for populations to respond to fluctuating environments, yet may be insufficient to adapt to a directionally changing environment. To study whether plasticity can evolve under current climate change, we quantified selection and genetic variation in both the elevation (RNE) and slope (RNS) of the breeding time reaction norm in a long‐term (1973–2016) study population of great tits (Parus major). The optimal RNE (the caterpillar biomass peak date regressed against the temperature used as cue by great tits) changed over time, whereas the optimal RNS did not. Concordantly, we found strong directional selection on RNE, but not RNS, of egg‐laying date in the second third of the study period; this selection subsequently waned, potentially due to increased between‐year variability in optimal laying dates. We found individual and additive genetic variation in RNE but, contrary to previous studies on our population, not in RNS. The predicted and observed evolutionary change in RNE was, however, marginal, due to low heritability and the sex limitation of laying date. We conclude that adaptation to climate change can only occur via micro‐evolution of RNE, but this will necessarily be slow and potentially hampered by increased variability in phenotypic optima.
Optimal Endobronchial Ultrasound Strain Elastography Assessment Strategy: An Explorative Study

Background: In lung cancer staging, mediastinal lymph nodes are currently aspirated using endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) based on size and FDG-PET avidity. EBUS strain elastography (SE) is a new technique that may help predict the presence of malignancy. However, a standardized assessment strategy for EBUS-SE measurement is lacking. Objectives: The aim of this study was to determine the optimal assessment strategy for investigating the predictive value of EBUS-SE in mediastinal lymph nodes. Methods: Two qualitative visual analogue scale strain scores and two semiquantitative strain elastography measurements (a strain histogram and strain ratio) were acquired in 120 lymph nodes of 63 patients with (suspected) lung cancer. The dataset was randomized into an 80% training dataset to determine cut-off values. Performance was consecutively tested on the remaining 20% and the overall dataset. Results: The semiquantitative mean histogram scoring strategy with a cut-off value of 78 (range 0–255) showed the best and most reproducible performance in prediction of malignancy with 93% overall sensitivity, 75% specificity, 69% positive predictive value, 95% negative predictive value, and 82% accuracy. Combining the EBUS-SE mean histogram scoring outcome with PET-CT information increased the post-test probability of disease in relevant clinical scenarios, having a positive test likelihood ratio of 4.16 (95% CI 2.98–8.13) and a negative test likelihood ratio of 0.14 (95% CI 0.04–2.81) in suspicious lymph nodes based on FDG-PET or CT imaging. Conclusions: EBUS-SE can potentially help predict lymph node malignancy in patients with lung cancer. The best semiquantitative assessment method is the mean strain histogram technique.
Rates and characteristics of postcolonoscopy colorectal cancer in the Swedish IBD population: what are the differences from a non-IBD population?

Objective The rate of postcolonoscopy colorectal cancer (PCCRC) is considered a key quality indicator of colonoscopy; little is known about PCCRC in IBD. Design A population-based cohort study of colonoscopies in Sweden from 2001 to 2010 was conducted. Individuals with a colorectal cancer (CRC) detected within 36 months after a colonoscopy were identified and stratified on UC, Crohn’s disease (CD) or non-IBD. The CRCs were classified as detected CRCs (dCRC) (0–6 months) or as PCCRCs (6–36 months). PCCRC rates were calculated by the number of false negative/(the number of true positive+the number of false negative) colonoscopies. Poisson regression analysis was employed to examine the association between PCCRC and IBD (CD and UC) diagnosis, age, gender, location, time period and comorbidities. Results We identified 348 232 colonoscopies in 270 918 individuals. Of these, 27 123 were performed on 14 597 individuals with CD, and 51 572 were performed on 26 513 individuals with UC. There were 13 317 CRCs in the non-IBD group, 133 in the CD group and 281 in the UC group. The PCCRC rate in the CD group was 28.3% and 41.0% in the UC group. The RR for a PCCRC was 3.82 (95% CI 2.94 to 4.96) in CD and 5.89 (95% CI 5.10 to 6.80) in UC, compared with non-IBD. The highest risk was observed among rectal cancer location in CD and in younger individuals with UC. Conclusion The high rates of PCCRC in young patients with UC and for rectal cancer location in CD might affect future performance of IBD surveillance.
Long-Term Cognitive Effects of Kratom (Mitragyna speciosa Korth.) Use

ABSTRACT Kratom or Mitragyna speciosa (Korth.) is a medicinal plant of Southeast Asia. As a result of its opioid-like effects, it remains unknown whether consumption of kratom tea is associated with impaired cognitive function. We assessed the cognitive function of 70 regular kratom users and 25 control participants using the Cambridge Neuropsychological Test Automated Battery. Participants performed six neuropsychological tasks that assessed motor, learning and memory, attention and executive function. Relative to control participants, higher consumption (>3 glasses daily or mitragynine doses between 72.5 mg and 74.9 mg) of kratom tea was selectively associated with impaired performance on the Paired Associates Learning task, reflecting deficits in visual episodic memory and new learning. Overall, the performance of kratom users compared to control participants, and the performance of high (>3 glasses per day) as well as low (≤3 glasses per day) kratom using groups, were comparable on all neuropsychological domains. Higher intake of kratom juice (>3 glasses daily) did not appear to impair motor, memory, attention or executive function of regular kratom users.
Sports mega-event legacies and adult physical activity: A systematic literature review and research agenda

Abstract Sports mega-events, such as the Olympic and Paralympic Games, have the potential to inspire increases in population physical activity, yet investigations concerning such legacy outcomes have been inconclusive. This may be due to research design limitations or inconsistent leveraging of potential hosting benefits by event organizers. This systematic review aims to identify current knowledge about the capacity of sports mega-events to inspire increases in physical activity participation among adult populations and develop a research agenda to guide future legacy evaluations. Peer-reviewed, English-language studies published on or after the year 2000 were considered. Six academic databases and grey literature sources were searched, and articles were assessed for methodological quality. Reporting followed PRISMA conventions for systematic reviews. Nine studies were selected after quality evaluation, including previous reviews, quantitative and qualitative research. Most studies found no evidence for long-term physical activity outcomes associated with hosting sports mega-events, although limitations and gaps were identified. These included lack of longitudinal or cohort studies, limited differentiation of subpopulations, use of non-validated instruments, and lack of triangulation for qualitative findings. Only one cohort study from Japan identified sustainable and significant physical activity increases resulting from a previous sports mega-event. Considering theory, the commonly cited Demonstration Effect was reportedly an unreliable framework, although the Festival Effect and Social Ecological Model appear more promising for anticipating and explaining legacy effects. With less than two years until the Tokyo 2020 Olympiad, it is appropriate to commence high-quality legacy research drawing on lessons learned from previous studies.
The Prevalence and Psychological Cost of Interpersonal Violence in Graduate and Law School

There is a rich research literature linking interpersonal violence to mental health disorders among undergraduate students. However, scholars know less about the prevalence and consequences of victimization among students enrolled in postbaccalaureate programs. Graduate and law students are uniquely vulnerable in their dependence on programs for financial support and career advancement, and they are more isolated than undergraduates. We explore the experiences of sexual harassment, sexual assault, and stalking in a sample of 1,149 male and female master’s, doctoral, and law students at a southeastern public university. First, the current study estimates prevalence rates of sexual harassment, sexual assault, and stalking across participant characteristics such as gender, race, sexual orientation, and degree program. We find higher rates of sexual harassment among lesbian, gay, bisexual, transgender, queer, intersex, or asexual (LGBTQ+) women and multiracial students and higher rates of coercion and stalking among women. Second, following a longstanding literature on experiences with violence among undergraduate women, we demonstrate the effects of interpersonal violence on depression and anxiety. A series of multivariate analysis of covariance (MANCOVA) suggests a heightened risk of mental health disturbances among law students, women, and LGBTQ+ students. Importantly, interpersonal violence partially explains these heightened levels of depression and anxiety in these groups. Given increasing rates of enrollment in postbaccalaureate programs, our findings suggest an unfulfilled need for the assessment, prevention, and treatment of individuals regarding the experiences of interpersonal violence and mental illness among graduate and law students. Student services should develop education and prevention programming for students and faculty to alleviate the occurrence and consequences of victimization while being mindful of the unique experiences of sexually and racially minoritized students.
Daily Supplementation with 4000 IU Vitamin D3 for Three Years Does Not Modify Cardiovascular Risk Markers in Patients with Advanced Heart Failure: The Effect of Vitamin D on Mortality in Heart Failure Trial

Background/Aims: We aimed to investigate the effect of a moderately high vitamin D dose on lipid parameters and biochemical markers of vascular calcification (VC) in patients with established cardiovascular disease. Methods: We included in this pre-specified secondary analysis of a randomized controlled trial 161 patients with advanced heart failure and 25-hydroxyvitamin D (25OHD) concentrations < 75 nmol/L (vitamin D group: n = 80; placebo group: n = 81), who received a daily vitamin D3 supplement of 4,000 IU for 3 years. We assessed between-group differences of the lipid parameters total-cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides, and the VC markers fetuin-A and non-phosphorylated undercarboxylated matrix gla protein (MGP) at study termination, with adjustment for baseline values. Results: Lipid parameters, the percentage of patients with dyslipoproteinemia, and VC markers did not differ significantly between groups at study termination (p values: 0.395–0.939). Likewise, vitamin D achieved no significant treatment effect on these markers in subgroup analyses in patients with 25OHD concentrations < 30 nmol/L, nonusers of lipid-lowering drugs, or diabetic patients (p values: 0.245–0.998). Conclusion: Our data indicate that vitamin D does not improve the lipid profile and does not influence the calcification inhibitors fetuin-A and non-phosphorylated undercarboxylated MGP in patients with advanced heart failure.