Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and cost-benefit of filgrastim administered after early assessment bone marrow biopsy during induction therapy for acute myeloid leukemia

Abstract The role of filgrastim during acute myeloid leukemia (AML) induction therapy remains controversial. At our institution, newly diagnosed AML patients from 2003 through 2019 were retrospectively evaluated. Patients were stratified on whether they received filgrastim within 5 days after early assessment bone marrow (BMBx) and divided into early GCSF group (eGCSF) and no-eGCSF group. A total of 121 patients were included. We found significantly shorter hospital stay (median 24 vs 26 days, p < .01), absolute neutrophil count recovery days (median 23 vs 25 days, p = .03), and intravenous antibiotics days (mean 18.5 vs 21.4 days, p = .01) in patients with eGCSF comparing with no-eGCSF. There was no significant difference regarding complete response rates; however, for those failed to achieve remission, eGCSF was associated with higher blast count. There was no significant difference regarding overall survival or progression-free survival. The use of eGCSF was associated with cost savings of $5199 per patient over no-eGCSF.
TET-mediated 5-methylcytosine oxidation in tRNA promotes translation.

Oxidation of 5-methylcytosine (5mC) in DNA by the ten-eleven translocation (TET) family of enzymes is indispensable for gene regulation in mammals. More recently, evidence has emerged to support a biological function for TET-mediated m5C oxidation in messenger RNA. Here, we describe a previously uncharacterized role of TET-mediated m5C oxidation in transfer RNA (tRNA). We found that the TET-mediated oxidation product 5-hydroxylmethylcytosine (hm5C) is specifically enriched in tRNA inside cells and that the oxidation activity of TET2 on m5C in tRNAs can be readily observed in vitro. We further observed that hm5C levels in tRNA were significantly decreased in Tet2 KO mouse embryonic stem cells (mESCs) in comparison with wild-type mESCs. Reciprocally, induced expression of the catalytic domain of TET2 led to an obvious increase in hm5C and a decrease in m5C in tRNAs relative to uninduced cells. Strikingly, we also show that TET2-mediated m5C oxidation in tRNA promotes translation in vitro. These results suggest TET2 may influence translation through impacting tRNA methylation and reveal an unexpected role for TET enzymes in regulating multiple nodes of the central dogma.
Persistent Obstructive Sleep Apnea Burden on Family Finances and Quality of Life

Objective We previously found that financial concerns negatively affect the quality of life of families of children with persistent obstructive sleep apnea (OSA) after tonsillectomy. The goal is to quantify the financial impact on families of children with persistent OSA and assess contributing factors. Study Design Cross-sectional survey study with comparison group. Setting Upper airway center at a tertiary pediatric hospital. Methods Participants included consecutive children with persistent OSA from September to October 2017. Healthy children seen in a general otolaryngology clinic served as controls. Families of both groups completed the Family Impact Questionnaire and the modified Comprehensive Score for Financial Toxicity (COST). Results Families of the 50 patients (25 study and 25 control) completed the surveys: the mean age was 6.4 years (95% CI, 5.0-7.8), and 19 (38%) were female. There were no differences in age, sex, race, or insurance status between groups (P > .05). The mean apnea-hypopnea index for the study group was 7.9 events/h (range, 5.5-10.3), and 40% (10/25) had Down syndrome. Positive airway pressure and/or oxygen were used by 72% (18/25). The Comprehensive Score for Financial Toxicity for study patients (21.9; 95% CI, 14.8-26.0) was significantly lower than for controls (30.2; 95% CI, 26.6-30.8; P = .003), reflecting elevated financial toxicity. Study families reported greater financial impact on the Family Impact Questionnaire (8.4; 95% CI, 6.1-10.7) versus controls (3.6; 95% CI, 1.8-5.4; P = .002); concerns regarding missed days of work and school were common (30.7%). Conclusion Families of children with persistent OSA reported a high financial burden related to their children’s disease and were more likely to report financial toxicity than families of controls. Concern regarding missed work and school associated with appointments and treatment was a significant factor.
Amelioration of diabetes‐induced inflammation mediated pyroptosis, sarcopenia, and adverse muscle remodelling by bone morphogenetic protein‐7

Diabetic myopathy involves hyperglycaemia and inflammation that causes skeletal muscle dysfunction; however, the potential cellular mechanisms that occur between hyperglycaemia and inflammation, which induces sarcopenia, and muscle dysfunction remain unknown. In this study, we investigated hyperglycaemia‐induced inflammation mediating high‐mobility group box 1 activation, which is involved in a novel form of cell death, pyroptosis, diabetic sarcopenia, atrophy, and adverse muscle remodelling. Furthermore, we investigated the therapeutic potential of bone morphogenetic protein‐7 (BMP‐7), an osteoporosis drug, to treat pyroptosis, and diabetic muscle myopathy.
Comparison of efficacy of deep brain stimulation and focused ultrasound in parkinsonian tremor: a systematic review and network meta-analysis

To compare the efficacy of deep brain stimulation (DBS) and MRI-guided focused ultrasound (MRIgFUS) in parkinsonian tremor. We performed a network meta-analysis based on a Bayesian framework. We searched the literature for articles published between January 1990 and October 2020 using three databases: PubMed, Embase and Cochrane Library (The Cochrane Database of Systematic Reviews). A total of 24 studies were included in our analysis, comprising data from 784 participants. Our findings revealed similar efficacy of DBS and MRIgFUS in parkinsonian tremor suppression. Compared with internal globus pallidus (GPi)-MRIgFUS, GPi-DBS -1.84 (–6.44, 2.86), pedunculopontine nucleus (PPN)_DBS –3.28 (–9.28, 2.78), PPN and caudal zona incerta (cZI)-DBS 0.40 (–6.16, 6.87), subthalamic nucleus (STN)_DBS 0.89 (–3.48, 5.30), STN and cZI-DBS 1.99 (–4.74, 8.65), ventral intermediate nucleus(VIM)_DBS 1.75 (–2.87, 6.48), VIM_FUS 0.72 (–5.27, 6.43), cZI-DBS 0.27 (–4.75, 5.36) were no significantly difference. Compared with VIM-MRIgFUS, GPi-DBS -2.55(-6.94, 2.21), GPi-FUS -0.72 (–6.43, 5.27), PPN_DBS -4.01(–9.97, 2.11), PPN and cZI-DBS -0.32 (-6.73, 6.36), STN_DBS 0.16 (–3.98, 4.6), STN and cZI-DBS 1.31(-5.18,7.87), VIM-DBS 1.00(-3.41, 5.84)and cZI-DBS –0.43 (–5.07, 4.68) were no significantly difference. With respect to the results for the treatment of motor symptoms, GPi-DBS, GPi-MRIgFUS, STN-DBS and cZI-DBS were significantly more efficacious than baseline (GPi-DBS 15.24 (5.79, 24.82), GPi-MRIgFUS 13.46 (2.46, 25.10), STN-DBS 19.62 (12.19, 27.16), cZI-DBS 14.18 (1.73, 26.89). The results from the surface under the cumulative ranking results showed that STN-DBS ranked first, followed by combined PPN and cZI-DBS, and PPN-DBS ranked last. MRIgFUS, an efficacious intervention for improving parkinsonian tremor, has not demonstrated to be inferior to DBS in parkinsonian tremor suppression. Hence, clinicians should distinguish individual patients’ symptoms to ensure that the appropriate intervention and therapeutic approach are applied.
Solvent Resistant Honeycomb Films from Photo‐Crosslinkable Polycinnamate

Microporous films consisting of two-dimensionally ordered void structures - so-called honeycomb films - were produced by evaporation of polymer solutions under high humidity. Two types of poly(vinyl cinnamate)s were used: A newly synthesized amphiphilic poly(vinyl cinnamate) and a mixture of a commercial poly(vinyl cinnamate) and an amphiphilic poly-ion complex. Photo-crosslinking of the honeycomb structure could be achieved by UV irradiation while completely retaining the film morphology. The crosslinked films showed excellent stability against organic solvents.
Analysing landscape effects on dispersal networks and gene flow with genetic graphs

Graph‐theoretic approaches have relevant applications in landscape genetic analyses. When species form populations in discrete habitat patches, genetic graphs can be used (a) to identify direct dispersal paths followed by propagules or (b) to quantify landscape effects on multi‐generational gene flow. However, the influence of their construction parameters remains to be explored. Using a simulation approach, we constructed genetic graphs using several pruning methods (geographical distance thresholds, topological constraints, statistical inference) and genetic distances to weight graph links (FST, DPS, Euclidean genetic distances). We then compared the capacity of these different graphs to (a) identify the precise topology of the dispersal network and (b) to infer landscape resistance to gene flow from the relationship between cost‐distances and genetic distances. Although not always clear‐cut, our results showed that methods based on geographical distance thresholds seem to better identify dispersal networks in most cases. More interestingly, our study demonstrates that a sub‐selection of pairwise distances through graph pruning (thereby reducing the number of data points) can counter‐intuitively lead to improved inferences of landscape effects on dispersal. Finally, we showed that genetic distances such as the DPS or Euclidean genetic distances should be preferred over the FST for landscape effect inference as they respond faster to landscape changes.
Physical activity differentially regulates VEGF, PlGF, and their receptors in the human placenta

Physical activity (PA) has beneficial effects on the function of many organs by modulating their vascular development. Regular PA during pregnancy is associated with favorable short‐ and long‐term outcomes for both mother and fetus. During pregnancy, appropriate vascularization of the placenta is crucial for adequate maternal–fetal nutrient and gas exchange. How PA modulates angiogenic factors, VEGF, and its receptors in the human placenta, is as of yet, unknown. We objectively measured the PA of women at 24–28 and 34–38 weeks of gestation. Participants were considered “active” if they had met or exceeded 150 min of moderate‐intensity PA per week during their 2nd trimester. Term placenta tissues were collected from active (n = 23) or inactive (n = 22) women immediately after delivery. We examined the expression of the angiogenic factors VEGF, PlGF, VEGFR‐1, and VEGFR‐2 in the placenta. Western blot analysis showed VEGF and its receptor, VEGFR‐1 was significantly (p < 0.05) higher both at the protein and mRNA levels in placenta from physically active compared to inactive women. No difference in VEGFR‐2 was observed. Furthermore, immunohistochemistry showed differential staining patterns of VEGF and its receptors in placental endothelial, stromal, and trophoblast cells and in the syncytial brush border. In comparison, PlGF expression did not differ either at the protein or mRNA level in the placenta from physically active or inactive women. The expression and localization pattern of VEGF and its receptors suggest that PA during pregnancy may support a pro‐angiogenic milieu to the placental vascular network.
Anti‐colon cancer activity tracking isolation of peptide from ginseng leaves and potential mechanisms evaluation in vitro and in vivo

The ginseng has been used for over hundred years, in the belief of promoting longevity. However, the anticancer activity of ginseng leaf peptide (GP) has been never explored. In current study, we isolated the GPs and explored the anti‐colon cancer activity in vitro and in vivo. MTT results showed that the GP‐1 (GP‐1~FKEHGY) performed most antiproliferative activity against colon cancer CT‐26 cells with an IC50 of 86.4 ± 9.46 μM (48 h). Further study indicated that GP‐1 activated the caspases, regulated the p53/murine double minute 2 (MDM2) state, and induced the CT‐26 cells apoptosis in a mitochondrial pathway. Meanwhile, the GP‐1 arrested the CT‐26 cells in G0/G1 phase accompanied with cyclin expression regulation. In addition, GP‐1 significantly suppressed the tumor growth and induced the tumor cells apoptosis in vivo. Notably, the GP‐1 would be a potential anti‐colon cancer candidate.
Formal Desymmetrization of the Diastereotopic Chains in Gemini Calcitriol Derivatives with Two Different Side Chains at C-20

Derivatives of calcitriol with two equal side chains emanating at C-20, also known as gemini, have emerged as interesting compounds, either as instruments for assessing the steric requirements of the vitamin D receptor or as drug candidates. We now describe the syntheses of gemini analogs where the two side chains differ from each other. While retaining the 2-hydroxy-2-methylpentyl moiety, common to both calcitriol and gemini, as one chain, we replaced the other with a 1,1,1-trifluoro-2-hydroxy-2-(trifluoromethyl)-3-pentynyl group. The features comprising this chain modification are commonly regarded to improve toxicity profiles and drug performance. The resulting epimeric pairs with a new stereogenic center at C-20 were resolved and the absolute configurations assigned. The side-chain desymmetrization protocols described herein serve as a basis for additional synthesis activity in this area. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Image-based pooled whole-genome CRISPRi screening for subcellular phenotypes

Kanfer et al. develop a pooled CRISPRi screening method to identify genes regulating intracellular protein localization, organelle morphology or other subcellular phenotypes. The method uses machine learning to identify genetically altered cells, a photoactivated fluorescent protein to label them, and FACS plus deep sequencing to identify the affected gene.
Brief, Performance-Based Cognitive Screening in Youth Aged 12–25: A Systematic Review

Abstract Objective: Cognitive screening is an efficient method of detecting cognitive impairment in adults and may signal need for comprehensive assessment. Cognitive screening is not, however, routinely used in youth aged 12–25, limiting clinical recommendations. The aims of this review were to describe performance-based cognitive screening tools used in people aged 12–25 and the contexts of use, review screening accuracy in detecting cognitive impairment relative to an objective reference standard, and evaluate the risk of bias of included studies. Method: Electronic databases (Scopus, Medline, PsychINFO, and ERIC) were searched for relevant studies according to pre-determined criteria. Risk of bias was rated using the Quality Assessment of Diagnostic Accuracy Studies-2. Dual screening, extraction, and quality ratings occurred at each review phase. Results: Twenty studies met the review inclusion criteria. A diverse range of screening tools (length, format) were used in youth aged 12–25 with or without health conditions. Six studies investigating cognitive screening were conducted as primary accuracy studies and reported some relevant psychometric parameters (e.g., sensitivity and specificity). Fourteen studies presented correlational data to investigate the cognitive measure utility. Studies generally presented limited data on classification accuracy, which impacted full screening tool appraisal. Risk of bias was high (or unclear) in most studies with poor adherence to the Standards for Reporting Diagnostic Accuracy Studies (STARD) criteria. Conclusions: Few, high quality studies have investigated the utility of cognitive screening in youth aged 12–25, with no screening measure emerging as superior at detecting cognitive impairment in this age group.
Predicting sample success for large‐scale ancient DNA studies on marine mammals

In recent years, nonhuman ancient DNA studies have begun to focus on larger sample sizes and whole genomes, offering the potential to reveal exciting and hitherto unknown answers to ongoing biological and archaeological questions. However, one major limitation to such studies is the substantial financial and time investments still required during sample screening, due to uncertainty regarding successful sample selection. This study investigates the effect of a wide range of sample properties including latitude, sample age, skeletal element, collagen preservation, and context on endogenous content and DNA damage profiles for 317 ancient and historic pinniped samples collected from across the North Atlantic and surrounding regions. Using generalised linear and mixed‐effect models, we found that a range of factors affected DNA preservation within each of the species under consideration. The most important findings were that endogenous content varied significantly within species according to context, the type of skeletal element, the collagen content and collection year. There also appears to be an effect of the sample's geographic origin, with samples from the Arctic generally showing higher endogenous content and lower damage rates. Both latitude and sample age were found to have significant relationships with damage levels, but only for walrus samples. Sex, ontogenetic age and extraction material preparation were not found to have any significant relationship with DNA preservation. Overall, skeletal element and sample context were found to be the most influential factors and should therefore be considered when selecting samples for large‐scale ancient genome studies.
ESTUDOS DE REMOÇÃO DE ELEMENTOS INORGÂNICOS E DEGRADAÇÃO DE COMPOSTOS ORGÂNICOS POR RADIAÇÃO GAMA EM ÓLEOS LUBRIFICANTES USADOS

The automotive lubricating oils have partial degradation of organic compounds and addition of undesirable inorganic elements, during its use. These substances classify the used lubricating oils as dangerous and highly toxic. According to global consensus, concerning the environmental conservation, the best is to perform a reuse treatment of these lubricating oils. For this purpose, the uses of an alternative and effective technology have been sought. In this work, the efficacy and technical feasibility of the advanced oxidation process (AOP), by gamma radiation, for used automotive lubricating oil treatment has been studied. Different quantities of hydrogen peroxide and water Mii! li-Q were added to oil samples. They were submitted to the Cobalt-60 irradiator, type Gammacell, with 100, 200 and 500 kGy absorbed doses. The inorganic analysis by X-ray fluorescence (WDXRF) showed inorganic elements removal, mainly to sulphur, calcium, iron and nickel elements at acceptable levels by environmental protection law for oils reusing. The gas chromatography (GC/MS) analysis showed that the advanced oxidation process promotes the organic compounds degradation. The main identified compounds were tridecane, 2-methyi-naphthalene, and trietilamina-tetramethyl urea, which have important industrial applications. The multivariate analysis, Cluster Analysis (CA), showed that advanced oxidation process application is a viable and promising treatment for used lubricating oil reusing. coMissto KNucmi Dt mm^ WUCL£AR, 'SPIPEN
The human G protein‐coupled ATP receptor P2Y11 is a target for anti‐inflammatory strategies

The ATP receptor P2Y11, which couples to Gq and Gs proteins, senses cell stress and promotes cytoprotective responses. P2Y11 receptors are upregulated during differentiation of M2 macrophages. However, it is unclear whether and how P2Y11 receptors contribute to the anti‐inflammatory properties of M2 macrophages.
Temporal consistency and ecological validity of personality structure in common marmosets (Callithrix jacchus): A unifying field and laboratory approach

Personality in animals has been extensively researched in recent decades. Temporal consistency of behaviors is almost always part of the personality definition and is usually explored in several different testing sessions or observation periods. However, it is still unclear whether the obtained personality constructs are stable across several years, which might be especially important for long‐living animals, such as primates. Further, little is known on whether the personality structures obtained in the laboratory reflect the structures obtained under ecologically relevant conditions in the wild. Therefore, we conducted a battery of personality tests on common marmosets (Callithrix jacchus) (N = 27), compared it with a test battery conducted 4 years beforehand on a subset of animals in captivity (N = 13) and ran an adapted version under field conditions at Baracuhy Biological Field Station, Brazil (N = 18). Under captive conditions, we found a remarkably similar personality structure across 4 testing years. Further, we found high long‐term temporal consistency in the first two personality components, Boldness and Exploration; however, monkeys that changed their social (i.e., breeding) status between the two testing periods showed a significant increase in Boldness scores. Under field conditions, we found a somewhat similar personality structure as compared to the laboratory, which to some extent corroborates ecological validity of our personality test design. Nevertheless, whether the structure in the wild is suppressed or expanded in comparison to captivity, and in which way the social setting influences personality structure, should be further explored. Taken together, our results contribute to the discussion about the reliability and ecological validity of personality structures in nonhuman primates.
Socio-economic disparities in the dispensation of antibiotics in Sweden 2016–2017: An intersectional analysis of individual heterogeneity and discriminatory accuracy

Aims: Antimicrobial resistance presents an increasingly serious threat to global public health, which is directly related to how antibiotic medication is used in society. Actions aimed towards the optimised use of antibiotics should be implemented on equal terms and according to the needs of the population. Previous research results on differences in antibiotic use between socio-economic and demographic groups in Sweden are not entirely coherent, and have typically focused on the effects of singular socio-economic variables. Using an intersectional approach, this study provides a more precise analysis of how the dispensation of antibiotic medication was distributed across socio-economic and demographic groups in Sweden in 2016–2017. Methods: Using register data from a nationwide cohort and adopting an intersectional analysis of individual heterogeneity and discriminatory accuracy, we map the dispensation of antibiotics according to age, sex, country of birth and income. Results: While women and high-income earners had the highest antibiotic dispensation prevalence, no large differences in the dispensation of antibiotics were identified between socio-economic groups. Conclusions: Public-health interventions aiming to support the reduced and optimised use of antibiotics should be directed towards the whole Swedish population rather than towards specific groups. Correspondingly, an increased focus on socio-economic or demographic factors is not warranted in interventions aimed at improving antibiotic prescription patterns among medical practitioners.
Real‐World Six‐ and Twelve‐Month Drug Retention, Remission, and Response Rates of Secukinumab in 2,017 Patients With Psoriatic Arthritis in Thirteen European Countries

There is a lack of real‐life studies on interleukin‐17 (IL‐17) inhibition in psoriatic arthritis (PsA). We assessed real‐life 6‐ and 12‐month effectiveness (i.e., retention, remission, low disease activity [LDA], and response rates) of the IL‐17 inhibitor secukinumab in PsA patients overall and across 1) number of prior biologic/targeted synthetic disease‐modifying antirheumatic drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries.