Miracle-dz/UniFAR-FTUs huggingface dataset:
Persistence of DNMT3A R882 mutations during remission does not adversely affect outcomes of patients with acute myeloid leukaemia

Somatic mutation of the DNMT3A gene at the arginine R882 site is common in acute myeloid leukaemia (AML). The prognostic significance of DNMT3A R882 mutation clearance, using traditional diagnostic next generation sequencing (NGS) methods, during complete remission (CR) in AML patients is controversial. We examined the impact of clearing DNMT3A R882 mutations at diagnosis to the detectable threshold of ˂3% during CR on outcome in 56 adult AML patients. Mutational remission, defined as clearance of pre‐treatment DNMT3A R882 and all other AML‐associated mutations to a variant allele frequency ˂3%, occurred in 14 patients whereas persistent DNMT3A R882 mutations were observed in 42 patients. There were no significant differences in disease‐free or overall survival between patients with and without DNMT3A R882 mutation clearance. Patients with persistent DNMT3A R882 who cleared all other AML mutations and did not acquire new mutations (n = 30), trended towards longer disease‐free survival (1·6 vs. 0·6 years, P = 0·06) than patients with persistence of DNMT3A R882, in addition to other mutations or acquisition of new AML‐associated mutations, such as those in TET2, JAK2, ASXL1 and TP53 (n = 12). These data demonstrate that DNMT3A R882 mutations, as assessed by traditional NGS methods, persist in the majority of AML patients in CR.
Relationship Between Hospital‐Level Percentage of Midwife‐Attended Births and Obstetric Procedure Utilization

INTRODUCTION Research has shown good outcomes among individual low-risk women who receive perinatal care from midwives, yet little is known about how hospital-level variation in midwifery care relates to procedure use and maternal health. This study aimed to document the association between the hospital-level proportion of midwife-attended births and obstetric procedure utilization. METHODS This analysis used 2 data sources: Healthcare Cost and Utilization Project State Inpatient Database data for New York in 2014, and New York State Department of Health data on the percentage of midwife-attended births at hospitals in the state in 2014. Using logistic regression, we estimated the association between the hospital-level percentage of midwife-attended births and 4 outcomes among low-risk women: labor induction, cesarean birth, episiotomy, and severe maternal morbidity. RESULTS Hospital-level percentage of midwife-attended births was not associated with reduced odds of labor induction or severe maternal morbidity. Women who gave births at hospitals with more midwife-attended births had lower odds of giving birth by cesarean (eg, adjusted odds ratio [aOR], 0.70; 95% confidence interval [CI], 0.59-0.82 at a hospital with 15% to 40% of births attended by midwives, compared to no midwife-attended births) and lower odds of episiotomy (eg, aOR, 0.41; 95% CI, 0.23-0.74 at a hospital with more than 40% of births attended by midwives, compared to no midwife-attended births). DISCUSSION Our results indicate that hospitals with more midwife-attended births have lower utilization of some obstetric procedures among low-risk women; this raises the possibility of improving value in maternity care through greater access to midwifery care.
Toxicity of ammonium dinitro-o-sec-butyl phenolate in California soils

When used as selective or general contact sprays, dinitro-o-sec-butyl phenol compounds decompose too rapidly to create any problem of residual toxicity. Decomposition of dinitro selectives, like many other herbicides, causes considerable stimulation of crop growth. High cost prevents the use of these compounds for soil sterilization. In pre-emergence sprays water-soluble compounds of dinitro-o-sec-butyl phenol are not safe for tender crops, but preliminary tests indicate parent substituted phenols may be used.
Epidemiology of Pediatric Critical Care Transport in Northern Alberta and the Western Arctic

Objective: Specialized pediatric critical care transport teams are essential to pediatric retrieval systems. This study aims to describe the contemporary transports performed by a Canadian pediatric critical care transport team and to compare the treatment and outcomes of children referred from high-level care (hospitals offering pediatric services where an adult ICU exists) and nonhigh-level care (all other hospitals) hospitals. Design: A descriptive cohort study. Setting: The Stollery Children’s Hospital in Edmonton, Alberta, Western Canada. Patients: Children younger than 17 years old transported by the transport team from referral hospitals within the Stollery Children’s Hospital catchment area to Stollery Children’s Hospital between 1998 and 2015. Interventions: None. Measurements and Main Results: Characteristics of transports, patient demographics presenting vital signs, and outcomes were described overall and compared by transport-related time and referral hospital types (high-level care and nonhigh-level care). In total, 3,352 transports met the inclusion criteria; 1,049 were retrieved from eight high-level care hospitals and 2,303 from 53 nonhigh-level care hospitals; the median one-way transport distance was 383 kilometers, and 70% of the transports were air transports. The annual number of transports has increased during the study period. The PICU admission rate was between 40% and 55%. Transports from high-level care hospitals had significantly higher odds of being admitted to the PICU (odds ratio, 1.96; 95% CI, 1.31–2.93). The odds of intubation at the referral hospital were higher in the high-level care group, but the odds of intubation upon PICU admission was similar between the two groups. Mortality during or after transport was not significantly different between high-level care and nonhigh-level care hospitals. Conclusions: The current transport system has multiple priorities with regard to efficiency and quality. The medical services at referral hospitals may affect the likelihood of PICU admission and subsequent PICU length of stay; however, no negative impact was observed in other outcomes including mortality.
Unsaturated Fatty Acids Affect Quorum Sensing Communication System and Inhibit Motility and Biofilm Formation of Acinetobacter baumannii

The increasing threat of Acinetobacter baumannii as a nosocomial pathogen is mainly due to the occurrence of multidrug-resistant strains that are associated with the real problem of its eradication from hospital wards. The particular ability of this pathogen to form biofilms contributes to its persistence, increases antibiotic resistance, and promotes persistent/device-related infections. We previously demonstrated that virstatin, which is a small organic compound known to decrease virulence of Vibrio cholera via an inhibition of T4-pili expression, displayed very promising activity to prevent A. baumannii biofilm development. Here, we examined the antibiofilm activity of mono-unsaturated chain fatty acids, palmitoleic (PoA), and myristoleic (MoA) acids, presenting similar action on V. cholerae virulence. We demonstrated that PoA and MoA (at 0.02 mg/mL) were able to decrease A. baumannii ATCC 17978 biofilm formation up to 38% and 24%, respectively, presented a biofilm dispersing effect and drastically reduced motility. We highlighted that these fatty acids decreased the expression of the regulator abaR from the LuxIR-type quorum sensing (QS) communication system AbaIR and consequently reduced the N-acyl-homoserine lactone production (AHL). This effect can be countered by addition of exogenous AHLs. Besides, fatty acids may have additional non-targeted effects, independent from QS. Atomic force microscopy experiments probed indeed that PoA and MoA could also act on the initial adhesion process in modifying the material interface properties. Evaluation of fatty acids effect on 22 clinical isolates showed a strain-dependent antibiofilm activity, which was not correlated to hydrophobicity or pellicle formation ability of the tested strains, and suggested a real diversity in cell-to-cell communication systems involved in A. baumannii biofilm formation.
Onabotulinum toxin-A injections for sleep bruxism

Objectives To test the safety and efficacy of onabotulinum toxin-A (BoNT-A) injections into the masseter and temporalis muscles in patients with symptomatic sleep bruxism. Methods Participants 18 to 85 years old with clinically diagnosed sleep bruxism confirmed by polysomnography were enrolled in this randomized, placebo-controlled, 1:1, parallel-design trial with open-label extension. Participants were injected with BoNT-A 200 units (60 into each masseter and 40 into each temporalis) or placebo and were evaluated at 4 to 8 weeks after the initial treatment visit. The primary efficacy endpoint was clinical global impression (CGI), and the secondary efficacy endpoint was a visual analog scale (VAS) of change in bruxism and in pain at 4 to 8 weeks after injection. Exploratory endpoints included modified Montreal Bruxism Questionnaire, Headache Impact Test-6, total Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Self-Rated Anxiety Scale, and polysomnography data, including EMG recordings of the masseter and temporalis muscle bruxing events. Adverse events were recorded. Results Thirty-one participants were recruited and 23 were randomized (19 female, age 47.4 ± 16.9 years). All 13 randomized to BoNT-A and 9 of 10 randomized to placebo completed the study. CGI (p < 0.05) and VAS of change (p < 0.05) favored the BoNT-A group. None of the exploratory endpoints changed significantly, but total sleep time and number/duration of bruxing episodes favored the BoNT-A group. Two participants randomized to BoNT-A reported a cosmetic change in their smile. No dysphagia or masticatory adverse events were reported. Conclusions BoNT-A effectively and safely improved sleep bruxism in this placebo-controlled pilot trial. A large multicenter trial is needed to confirm these encouraging data. ClinicalTrials.gov identifier NTC00908050. Class of evidence This study provides Class II evidence that botulinum injections into the masseter and temporalis muscles improve subjective bruxism and painful symptoms associated with sleep bruxism.
Of guns and snakes: testing a modern threat superiority effect*

ABSTRACT Previous studies suggest that ancient (i.e. evolutionary-based) threats capture attention because human beings possess an inborn module shaped by evolution and dedicated to their detection. An alternative account proposes that a key feature predicting whether a stimulus will capture attention is its relevance rather than its ontology (i.e. phylogenetic or ontogenetic threat). Within this framework, the present research deals with the attentional capture by threats commonly encountered in our urban environment. In two experiments, we investigate the attentional capture by modern threats (i.e. weapons). In Experiment 1, participants responded to a target preceded by a cue, which was a weapon or a non-threatening stimulus. We found a larger cuing effect (faster reaction times to valid vs. invalid trials) with weapons as compared with non-threatening cues. In Experiment 2, modern (e.g. weapons) and ancient threats (e.g. snakes) were pitted against one another as cues to determine which ones preferentially capture attention. Crucially, participants were faster to detect a target preceded by a modern as opposed to an ancient threat, providing initial evidence for a superiority of modern threat. Overall, the present findings appear more consistent with a relevance-based explanation rather than an evolutionary-based explanation of threat detection.
A two-stage optimal vector selection method for predictive torque control of a three-level VSI driven induction motor

Conventional Finite State Predictive Torque control (FS-PTC) for three-level Neutral Point Clamped voltage source inverter (3L-NPC VSI) uses 27 voltage vectors for prediction and actuation. Using all voltage vectors for the prediction loop is not an ideal method as it increases computational burden. This paper proposes a less complex prediction loop method with selected number of voltage vectors for FS-PTC of a three level NPC driven induction motor. The number of voltage vectors is reduced based on a two-stage optimal vector selection algorithm. In the first stage, the algorithm considers the VSI as two-level and selects the most favourable long vector. In the second stage, among the short and the medium voltage vectors closest to the long vector which is selected in the first stage, the optimum vector is selected for prediction. Compared to 27 voltage vectors based prediction, this algorithm evaluates 15 selected vectors in total for prediction and actuation. The effectiveness of the proposed algorithm in terms of speed, torque and flux responses and capacitor voltage balancing is presented through simulation results from MATLAB/Simulink. Computational time is measured from a real-time simulation implemented on dSPACE DS1104 platform. The results show that the proposed method reduces the computation time significantly (by about 45%), while the dynamic and steady-state performances of the motor drive are retained similar to the conventional FS-PTC.
Contrasting pH buffering patterns in neutral-alkaline soils along a 3600 km transect in northern China

Abstract. Soil pH buffering capacity (pHBC) plays a crucial role in predicting acidification rates, yet its large-scale patterns and controls are poorly understood, especially for neutral-alkaline soils. Here, we evaluated the spatial patterns and drivers of pHBC along a 3600 km long transect (1900 km sub-transect with carbonate-containing soils and 1700 km sub-transect with non-carbonate-containing soils) across northern China. Soil pHBC was greater in the carbonate-containing soils than in the non-carbonate-containing soils. Acid addition decreased soil pH in the non-carbonate-containing soils more markedly than in the carbonate-containing soils. Within the carbonate soil sub-transect, soil pHBC was positively correlated with cation exchange capacity (CEC), carbonate content and exchangeable sodium (Na) concentration, but negatively correlated with initial pH and clay content, and not correlated with soil organic carbon (SOC) content. Within the non-carbonate sub-transect, soil pHBC was positively related to initial pH, clay content, CEC and exchangeable Na concentration, but not related to SOC content. Carbonate content was the primary determinant of pHBC in the carbonate-containing soils and CEC was the main determinant of buffering capacity in the non-carbonate-containing soils. Along the transect, soil pHBC was different in regions with different aridity index. Soil pHBC was positively related to aridity index and carbonate content across the carbonate-containing soil sub-transect. Our results indicated that mechanisms controlling pHBC differ among neutral-alkaline soils of northern China, especially between carbonate- and non-carbonate-containing soils. This understanding should be incorporated into the acidification risk assessment and landscape management in a changing world.
Frequency and Mechanism of Spontaneous Resistance to Sulbactam Combined with the Novel β-Lactamase Inhibitor ETX2514 in Clinical Isolates of Acinetobacter baumannii

ABSTRACT The novel diazabicyclooctenone ETX2514 is a potent, broad-spectrum serine β-lactamase inhibitor that restores sulbactam activity against resistant Acinetobacter baumannii. The frequency of spontaneous resistance to sulbactam-ETX2514 in clinical isolates was found to be 7.6 × 10−10 to <9.0 × 10−10 at 4× MIC and mapped to residues near the active site of penicillin binding protein 3 (PBP3). Purified mutant PBP3 proteins demonstrated reduced affinity for sulbactam. In a sulbactam-sensitive isolate, resistance also mapped to stringent response genes associated with resistance to PBP2 inhibitors, suggesting that in addition to β-lactamase inhibition, ETX2514 may enhance sulbactam activity in A. baumannii via inhibition of PBP2.
Macro Uncertainty and the Term Structure of Risk Premium

Leading frictionless consumption-based asset pricing models (Long run risks and Habit formation) predict that the expected return on assets whose cash ows appear in the distant future are higher than or equal to the expected returns on assets which pay-o in the near future. Contrary to that prediction, some recent empirical studies have found that short-term assets earn a higher expected return than long-term assets. Here, I show that allowing the cash ows to be negatively a ected by volatility shocks, as observed in the data ( leverage e ect ), could make the short-term assets riskier than long-term assets. This modi cation gives more exibility to those models in capturing various shapes of the term structure of equity returns while still matching the observed level of the equity premium and the risk free rate. *I am very grateful to Marianne Andries, Christian Gollier and Nour Meddahi for their advices, guidance and encouragements. I also thank, Patrick Fève, René Garcia, Sophie Moinas, Sébastien Pouget, Roméo Tédongap, participants to TSE Econometrics , Macro and Finance workshops, seminar participants at IAAE 2017, EEA-ESEM 2017 for helpful comments. I gratefully acknowledge the nancial support of the ERC grant n° 295298. All errors are mine. Toulouse School of Economics, UT1 Capitole, Manufacture des Tabacs, 21 Allée de Brienne 31000 Toulouse France. Email: jules.tinang@tse-fr.eu . An update version of the paper available here: https://sites.google. com/view/ jules-tinang/research 1
Factors predicting pain and effect of oral analgesia in topical photodynamic therapy

To The Editor, Topical photodynamic therapy (PDT) is highly efficacious for the treatment of actinic keratosis (AK), Bowen’s disease (BD) and superficial basal cell carcinoma (sBCC), and efficacious in thin nodular BCCs (nBCC) (1). It is generally well tolerated, with pain or discomfort being a known side effect (1). Pain is typically described as a burning or stinging sensation of varying intensity. Prior studies looking at factors which influence pain during PDT have shown conflicting results (2–5). The aim of our study was to identify any patient or treatment factors associated with higher levels of pain during PDT and to assess the effect of pretreatment analgesia. Treatment is standardised in our centre and documented in a standard treatment proforma. Patients receive one treatment per course for AK and two treatments per course, one week apart, for BD and BCC. Methyl aminolevulinate (MAL–Metvix Photocure ASA, Oslo, Norway) is used as a photosensitising agent. Wood’s lamp fluorescence (WLF) is used to assess absorption of the photosensitiser (excellent/good/poor). The Aktilite (Photocure ASA) (LED red light, 630 nm, 37J/cm) or Waldmann 1200L (Waldmann Medizintechnik, Villingen-Schwenningen, Germany) (filtered halogen lamp, non-coherent red light, 570–730 nm, 50J/cm) light-source is used. Patients complete a visual analogue pain scale (VAPS) to grade their pain during and after treatment. The highest pain score experienced during treatment is documented (range 0–100). Patients who are unable to complete a VAPS, for example, due to eyesight difficulty, are asked to grade their pain on a similar scale. Patients are offered oral analgesia 30 min pretreatment, and type of analgesia taken is documented. A fan and cooling water spray are provided during treatment. Following ethics approval, retrospective chart review was completed. Data were compiled in Microsoft Excel and analysed using SPSS (IBM SPSS Statistics for Macintosh, Version 22.0. Armonk, NY: IBM Corp.). All AK, BD and BCC treated between 2009 and mid-2015 were included in analysis. Complete data sets were available on all patients. Pearson’s chi-square, independent samples t-test and one-way ANOVA were used to obtain Pvalues, unless otherwise stated. Odds ratio (OR) and 95% confidence intervals (CI) were calculated using binary logistic regression. For the purpose of binary logistic regression, a dichotomous pain response was defined by dividing the VAPS into two groups at the median 40 (1–40 and 41–100). In total, 200 cases of AK, BD and BCC, in 109 patients were analysed. The average age was 74.6 years (Standard Deviation [SD] 9.55 range 33–96). The femaleto male-percentage split was 61 : 39. Sixty nine per cent of lesions were located on the limbs, 17% on the trunk and 14% on the head/neck. Fifty four per cent of lesions were BD, 24% BCC and 22% AK.
DMP‐1 ‐mediated Ghr gene recombination compromises skeletal development and impairs skeletal response to intermittent PTH

Bone minerals are acquired during growth and are key determinants of adult skeletal health. During puberty, the serum levels of growth hormone (GH) and its downstream effector IGF‐1 increase and play critical roles in bone acquisition. The goal of the current study was to determine how bone cells integrate signals from the GH/IGF‐1 to enhance skeletal mineralization and strength during pubertal growth. Osteocytes, the most abundant bone cells, were shown to orchestrate bone modeling during growth. We used dentin matrix protein (Dmp)‐1‐mediated Ghr knockout (DMP‐GHRKO) mice to address the role of the GH/IGF axis in osteocytes. We found that DMP‐GHRKO did not affect linear growth but compromised overall bone accrual. DMP‐GHRKO mice exhibited reduced serum inorganic phosphate and parathyroid hormone (PTH) levels and decreased bone formation indices and were associated with an impaired response to intermittent PTH treatment. Using an osteocyte‐like cell line along with in vivo studies, we found that PTH sensitized the response of bone to GH by increasing Janus kinase‐2 and IGF‐1R protein levels. We concluded that endogenously secreted PTH and GHR signaling in bone are necessary to establish radial bone growth and optimize mineral acquisition during growth. —Liu, Z. , Kennedy, O. D. , Cardoso, L. , Basta‐Pljakic, J., Partridge, N. C. , Schaffler, M. B. , Rosen, C. J., Yakar, S. DMP‐1‐mediated Ghr gene recombination compromises skeletal development and impairs skeletal response to intermittent PTH. FASEB J. 30, 635‐652 (2016). www.fasebj. org
Atrial fibrillation, anticoagulant stroke prophylaxis and bleeding risk with ibrutinib therapy for chronic lymphocytic leukaemia and lymphoproliferative disorders

The management of chronic lymphocytic leukaemia (CLL) has been revolutionised over the last several years by the introduction of targeted inhibitors of the B-cell receptor signal and BCL2 pathways. Ibrutinib is the first in class covalent inhibitor of the Bruton Tyrosine Kinase (BTK) molecule, which it binds irreversibly at the BTK cysteine-481 ATPbinding site and inhibits phosphorylation of down-stream PLC-c2, and B-cell receptor signalling (Byrd et al, 2013). Ibrutinib has been shown to improve progression free and overall survival in relapsed and refractory (R/R) CLL compared to ofatumumab (Byrd et al, 2014), and the combination of ibrutinib with bendamustine and rituximab (BR) is superior to BR (Chanan-Khan et al, 2016). Patients with R/R CLL therefore represent a high level of previously unmet need in CLL as they now achieve markedly superior outcomes than before ibrutinib was available. Sustained dose adherence may be important in maintaining response and optimal outcomes and avoiding the emergence of resistant clones (Jaeger et al, 2015). R/R CLL patients who are unable to tolerate ibrutinib have poor clinical outcomes and survival (Jain et al, 2015). More recently, ibrutinib has been compared to chlorambucil monotherapy in front-line CLL in patients deemed inappropriate for fludarabine-based therapy due to either comorbidity or advanced age. The results significantly favoured ibrutinib (Burger et al, 2015). Ibrutinib is now approved for relapsed and also front-line CLL therapy in the USA, and is therefore finding widespread use in CLL and other low-grade lymphoproliferative disorders.