Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparing a fixed combination of budesonide/formoterol with other inhaled corticosteroid plus long-acting beta-agonist combinations in patients with chronic obstructive pulmonary disease: a review

ABSTRACT Introduction: Inhaled corticosteroid (ICS) plus long-acting β2-agonist (LABA) combinations are commonly used in the treatment of patients with chronic obstructive pulmonary disease (COPD). At least four fixed-dose ICS/LABA combinations are available, including budesonide/formoterol, beclomethasone/formoterol, fluticasone/vilanterol and fluticasone/salmeterol, but there is little guidance for clinicians on which of these combinations to prescribe. Areas covered: The aim of this in-depth review was to identify studies that compared budesonide/formoterol with the other ICS/LABA combinations and assess the data on exacerbations, safety, and patient quality of life. PubMed and Ovid databases were searched, and 14 studies were identified. Our findings highlight the lack of prospective, randomized, controlled trials comparing LABA/ICS combinations in the treatment of COPD as only two such studies were identified. However, current evidence suggests that the effects of budesonide/formoterol on reducing exacerbations and improving quality of life may be similar to, or more marked than, those of other LABA/ICS combinations in COPD and, compared with the other LABA/ICS combinations, budesonide/formoterol may be associated with a lower incidence of serious pneumonia events and oral candidiasis. Expert opinion: To better guide clinicians in selecting between the available ICS/LABA, robust meta-analyses and well-designed head-to-head clinical trials are urgently needed.
Hearing loss in very preterm infants: should we wait or treat?

SUMMARY This study investigated hearing threshold changes during the first year of corrected age (CA) in infants admitted in a neonatal intensive care unit (NICU). In 5 years, 239 infants with birth weight (BW) ≤ 1,000 gm and/or gestational age (GA) ≤ 30 weeks were enrolled. Hearing was evaluated by oto-acoustic emission (OAEs) before discharge and auditory brainstem response (ABR) within 3 months of CA. Infants affected by unilateral or bilateral hearing loss were addressed to audiological follow-up until definitive diagnosis (within 6 months of CA). Changes in hearing threshold were also carefully analysed. 207 (86.6%) infants had normal hearing while 32 infants (13.4%) showed hearing loss (HL) at the confirmative ABR evaluation (9 mild, 16 moderate, 4 severe, 3 profound). The latter showed lower GA (27.7 ± 2 vs 28.4 ± 1.2; p = 0.0061) and BW (950 ± 390 vs 1,119 ± 326 gm; p = 0.0085). At final evaluation, 15 infants (47%) recovered a normal hearing. HL was confirmed in 17 patients. Among these, 3 infants were addressed to audiological follow-up (one case of mild unilateral hearing loss (UHL) and two with moderate UHL), while in 14 cases (44%) with bilateral sensory neural hearing loss (SNHL) (7 moderate, 4 severe, 3 profound) hearing aids were prescribed. They showed significantly lower GA and longer hospital stay in the NICU in comparison with infants without indication for audiological habilitation (18 infants) (GA 26.2 ± 2.2 weeks vs 28.4 ± 2.4; p = 0.01; NICU stay 132 ± 67 vs 59 ± 7; p = 0.0002). Definitive diagnosis was obtained at 5.9 ± 1.3 months of CA. Our study confirms the importance of audiological surveillance in preterm newborns. Hearing thresholds of preterm infants with hearing loss can change during the first year of CA and we observed normalisation in 47% of our patients. Most vulnerable to permanent SNHL were very preterm infants with a longer NICU stay, while a shorter stay represents a favourable prognostic factor for hearing improvement.
Effects of dental general anaesthesia treatment on early childhood caries: a prospective cohort study in China

Objectives To evaluate the success rates of dental procedures, the recurrence rates of caries and changes in oral health-related quality of life (OHRQoL) in children following treatment for early childhood caries (ECC) under dental general anaesthesia (DGA) in Chongqing, China. Design A single-centre prospective cohort study conducted from December 2016 to June 2017. Setting A tertiary stomatological hospital in Chongqing, China. Participants A total of 159 children aged 2–5 years who received treatment for ECC under DGA were included. Main outcome measures The primary outcomes were the success rates of dental procedures (the number of successful procedures divided by the total number of procedures) and the recurrence rates of caries. The success and recurrence rates were evaluated by a specialised examiner. The secondary outcome was the change in children’s OHRQoL after DGA treatment, which was measured with the Early Childhood Oral Health Impact Scale (ECOHIS). Results Overall, 117 children (73.6%) and 101 children (63.5%) participated in 6-month and 12-month clinical examinations, respectively, and 151 children (95.0%) completed OHRQoL surveys pretreatment and at 1, 3, 6 and 12 months post-treatment. The resin composite, stainless steel crown, indirect pulp capping, pulpectomy, space maintenance and dental sealant success rates were 89.6%, 96.3%, 96.0%, 94.4%, 76.9% and 92.9%, respectively, at 6 months and 78.8%, 95.1%, 92.2%, 88.9%, 63.6% and 89.3%, respectively, at 12 months. 10 (8.5%) and 19 children (18.8%) developed recurrent caries within 6 and 12 months, respectively. Within 1 year of treatment, the total ECOHIS scores at each post-treatment time point were still significantly lower than those at pretreatment, although they had increased slowly over time. Conclusions Overall, high success rates were obtained for the dental procedures, and the children’s OHRQoL significantly improved after treatment. However, there was a tendency towards caries relapse, and the children’s OHRQoL deteriorated over time.
Phosphorus and Nitrogen Modulate Plant Performance in Shrubby Legumes from the Iberian Peninsula

We investigated the impact of phosphorus nutrition on plant growth and biological nitrogen fixation in four leguminous plants in the Tribe Genistea. The main objective of the study was to analyze Phosphorus and Nitrogen use efficiency under drought. We also tested for the effects of rhizobial inoculation on plant performance. Plants inoculated with Rhizobium strains isolated from plants of the four species growing in the wild were cropped under controlled conditions in soils with either low P (5 µM) or high P (500 µM). The experiment was replicated in the presence and absence of plant irrigation to test for the effects of drought stress of inoculated and non-inoculated plants under the two P levels of fertilization. Low-P treatments increased nodule production while plant biomass and shoot and root P and N contents where maximum at high P. Low P (5 µM) in the growing media, resulted in greater N accumulated in plants, coupled with greater phosphorus and nitrogen uptake efficiencies. Drought reduced the relative growth rate over two orders of magnitude or more, depending on the combination of plant species and treatment. Genista cinerea had the lowest tolerance to water scarcity, whereas Genista florida and Retama sphaerocarpa were the most resistant species to drought. Drought resistance was enhanced in the inoculated plants. In the four species, and particularly in Echinospartum barnadesii, the inoculation treatment clearly triggered N use efficiency, whereas P use efficiency was greater in the non-inoculated irrigated plants. Nodulation significantly increased in plants in the low P treatments, where plants showed a greater demand for N. The physiological basis for the four species being able to maintain their growth at low P levels and to respond to the greater P supply, is through balanced acquisition of P and N to meet the plants’ nutritional needs.
A new potential anti‐cancer beta‐carboline derivative decreases the expression levels of key proteins involved in glioma aggressiveness: A proteomic investigation

Gliomas remain highly fatal due to their high resistance to current therapies. Deregulation of protein synthesis contributes to cancer onset and progression and is a source of rising interest for new drugs. CM16, a harmine derivative with predicted high blood–brain barrier penetration, exerts antiproliferative effects partly through translation inhibition. We evaluated herein how CM16 alters the proteome of glioma cells. The analysis of the gel‐free LC/MS and auto‐MS/MS data showed that CM16 induces time‐ and concentration‐dependent significant changes in the total ion current chromatograms. In addition, we observed spontaneous clustering of the samples according to their treatment condition and their proper classification by unsupervised and supervised analyses, respectively. A two‐dimensional gel‐based approach analysis allowed us to identify that treatment with CM16 may downregulate four key proteins involved in glioma aggressiveness and associated with poor patient survival (HspB1, BTF3, PGAM1, and cofilin), while it may upregulate galectin‐1 and Ebp1. Consistently with the protein synthesis inhibition properties of CM16, HspB1, Ebp1, and BTF3 exert known roles in protein synthesis. In conclusion, the downregulation of HspB1, BTF3, PGAM1 and cofilin bring new insights in CM16 antiproliferative effects, further supporting CM16 as an interesting protein synthesis inhibitor to combat glioma.
Shrinking body size and physiology contribute to geographic variation and the higher toxicity of pesticides in a warming world.

To improve current and future risk assessment of pesticides under global warming, mechanistic insights and consideration of daily temperature fluctuations (DTFs) are needed. One overlooked mechanism how both higher mean temperatures and DTFs may increase toxicity is by reducing body size (temperature-size-rule). We studied whether a higher mean temperature and DTF magnified chlorpyrifos toxicity in Ischnura elegans damselfly larvae, and whether this was mediated by temperature-induced reductions in body size and/or physiological changes. The lethal effects of chlorpyrifos were magnified at the high mean temperature (up to ~15 %) and under DTF (up to ~33 %), and especially at their combination (up to ~46 %) indicating synergisms. This highlights that not only considering DTFs, but also their interaction with higher mean temperatures is pivotal for realistic predictions of pesticide toxicity. Both higher temperatures and DTFs resulted in smaller larvae, which were more sensitive to chlorpyrifos. Notably, the DTF-induced smaller body sizes, as well as the higher oxidative damage to lipids, contributed to the higher chlorpyrifos toxicity under DTF. By integrating the temperature-size rule and size-pesticide sensitivity pattern we provide proof-of-principle for a novel, likely general mechanism contributing to geographic variation and the higher toxicity of pesticides in a warming world.
SCN11A mRNA levels in female bipolar disorder PBMCs as tentative biomarker for distinct patient sub‐phenotypes

Bipolar disorder (BD) is a complex neuropsychiatric disorder characterized by recurrent mania and depression episodes and requiring lifelong treatment with mood stabilizing drugs. Several lines of evidence, including with BD patient iPSC‐derived neurons, suggest that neuronal hyperexcitability may underlie the key clinical symptoms of BD. Indeed, higher mRNA levels of SCN11A, coding for the voltage‐gated sodium channel NaV1.9 implicated in nociception, were detected in iPSC‐derived neurons from BD patients, and were normalized by in vitro lithium. Here we studied SCN11A expression in peripheral blood mononuclear cells (PBMCs) from well‐phenotyped female BD patients and controls and evaluated their association with several clinical sub‐phenotypes. We observed higher mRNA levels of SCN11A in PBMCs from female BD patients with no records of alcohol dependence (p = .0050), no records of psychosis (p = .0097), or no records of suicide attempts (p = .0409). A trend was observed for higher SCN11A expression (FD = 1.91; p = .052) in BD PBMCs compared with controls. Datamining of published postmortem gene expression datasets indicated higher SCN11A expression in dorsolateral prefrontal cortex and orbitofrontal cortex tissues from BD patients compared with controls. Higher phenotype‐associated expression levels in PBMC from BD patients were also observed for ID2 (alcohol dependence, suicide attempts) and HDGFRP3 (seasonal BD pattern). Our findings suggest that higher PBMC SCN11A expression levels may be associated with certain behavioral BD sub‐phenotypes, including lack of alcohol dependence and psychosis, among BD patients. The NaV1.9 voltage‐gated sodium channel thus deserves consideration as a tentative phenotype modifier in BD.
Induction of Rhodobacter capsulatus Gene Transfer Agent Gene Expression Is a Bistable Stochastic Process Repressed by an Extracellular Calcium-Binding RTX Protein Homologue

GTAs catalyze horizontal gene transfer (HGT), which is important for genomic evolution because the majority of genes found in bacterial genomes have undergone HGT at some point in their evolution. Therefore, it is important to determine how the production of GTAs is regulated to understand the factors that modulate the frequency of gene transfer and thereby specify the tempo of evolution. This work describes a new type of genetic regulation in which an extracellular calcium-binding protein homologue represses the induction of the Rhodobacter capsulatus GTA, RcGTA. ABSTRACT Bacteriophage-like gene transfer agents (GTAs) have been discovered in both of the prokaryotic branches of the three-domain phylogenetic tree of life. The production of a GTA (RcGTA) by the phototrophic alphaproteobacterium Rhodobacter capsulatus is regulated by quorum sensing and a phosphorelay homologous to systems in other species that control essential functions such as the initiation of chromosome replication and cell division. In wild-type strains, RcGTA is produced in <3% of cells in laboratory cultures. Mutants of R. capsulatus that exhibit greatly elevated production of RcGTA were created decades ago by chemical mutagenesis, but the nature and molecular consequences of the mutation were unknown. We show that the number of cells in a population that go on to express RcGTA genes is controlled by a stochastic process, in contrast to a genetic process. We used transposon mutagenesis along with a fluorescent protein reporter system and genome sequence data to identify a gene, rcc00280, that encodes an RTX family calcium-binding protein homologue. The Rc280 protein acts as an extracellular repressor of RcGTA gene expression by decreasing the percentage of cells that induce the production of RcGTA. IMPORTANCE GTAs catalyze horizontal gene transfer (HGT), which is important for genomic evolution because the majority of genes found in bacterial genomes have undergone HGT at some point in their evolution. Therefore, it is important to determine how the production of GTAs is regulated to understand the factors that modulate the frequency of gene transfer and thereby specify the tempo of evolution. This work describes a new type of genetic regulation in which an extracellular calcium-binding protein homologue represses the induction of the Rhodobacter capsulatus GTA, RcGTA.
Radiotherapy-Induced Changes in the Systemic Immune and Inflammation Parameters of Head and Neck Cancer Patients

Though radiotherapy is a local therapy, it has systemic effects mainly influencing immune and inflammation processes. This has important consequences in the long-term prognosis and therapy individualization. Our objective was to investigate immune and inflammation-related changes in the peripheral blood of head and neck cancer patients treated with radiotherapy. Peripheral blood cells, plasma and blood cell-derived RNA were isolated from 23 patients before and at two time points after radiotherapy and cellular immune parameters, plasma protein changes and gene expression alterations were studied. Increased regulatory T cells and increased CTLA4 and PD-1 expression on CD4 cells indicated an immune suppression induced by the malignant condition, which was accentuated by radiotherapy. Circulating dendritic cells were strongly elevated before treatment and were not affected by radiotherapy. Decreased endoglin levels in the plasma of patients before treatment were further decreased by radiotherapy. Expression of the FXDR, SESN1, GADD45, DDB2 and MDM2 radiation-response genes were altered in the peripheral blood cells of patients after radiotherapy. All changes were long-lasting, detectable one month after radiotherapy. In conclusion we demonstrated radiotherapy-induced changes in systemic immune parameters of head and neck cancer patients and proposed markers suitable for patient stratification worth investigating in larger patient cohorts.
A Highly Sensitive and Stretchable Yarn Strain Sensor for Human Motion Tracking Utilizing a Wrinkle-Assisted Crack Structure.

With the booming development of flexible electronics, the need for a multifunctional and high-performance strain sensor has become increasingly important. Although significant progress has been made in designing new microstructures with sensing capabilities, the trade-off between sensitivity and workable strain range has prevented the development of a strain sensor that is both highly sensitive and also stretchable. Here, a wrinkle-assisted crack microstructure is designed and fabricated via pre-stretching the multi-walled carbon nanotubes ink (CNTs ink)/polyurethane yarn (PU yarn). This designed structure originates from the mismatch in Young's modulus and elasticity between the CNTs ink and PU yarn during the stretching process. The structure endows the sensor with combined characteristics of a high sensitivity towards stretching strain (gauge factor (GF) of 1344.1 at 200% strain), an ultralow limit of detection (<0.1% strain), excellent durability (>10,000 cycles), a wide workable strain range (0-200%), and outstanding response and stability toward bending deformation. This high-performance strain sensor will see widespread improved performance across applications such as intelligent fabrics, electrical skins, and fatigue detection for full-range human motion monitoring.
Diagnosis and management of hypertension in pregnancy: summary of updated NICE guidance

### What you need to know Hypertension in pregnancy is a common condition, affecting about 10% of pregnant women. This includes women with chronic hypertension—which may be diagnosed before pregnancy or in the early stages of pregnancy (<20 weeks’ gestation)—and women with hypertension related to pregnancy (gestational hypertension and pre-eclampsia) (see box 1). If not identified and treated, hypertension can lead to adverse events for both the woman and her baby, including increased risk of maternal stroke, lower birth weight, and increased risk of the baby requiring neonatal intensive care. Box 1 ### Definitions for hypertensive disorders of pregnancyRETURN TO TEXT General practitioners and specialists other than obstetricians play a vital role in the identification of hypertension during pregnancy, first …
Incidence of ESKD and Mortality among Children with Congenital Heart Disease after Cardiac Surgery.

BACKGROUND AND OBJECTIVES Survival after surgical repair for congenital heart disease has markedly improved; however, there are limited data on long-term ESKD and mortality during childhood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted an observational, population-based cohort study of children who had their first surgery for congenital heart disease within 10 years of birth. The study was conducted in Ontario, Canada, where residents have universal access to health care services. Each child who underwent surgical repair was matched to ten children from the general population who were similar in age, sex, index date, rurality, and neighborhood income. Primary outcomes of all-cause mortality and ESKD were reported until March 2015. RESULTS We followed 3600 children with congenital heart disease for a median of 5.9 (interquartile range, 2.9-9.0) years after their surgical repair. Median age at first surgery was 150 (interquartile range, 40-252) days and 22% were low birth weight (<2500 g). During follow-up, 140 (4%) children who had surgery for congenital heart disease died and 52 (1%) reached ESKD. The cumulative incidence of death and ESKD at 1, 5, and 10 years was higher in children with surgical repair of congenital heart disease (death: 3%, 4%, and 5%, respectively; ESKD: 1%, 2%, and 2%, respectively) compared with the matched control population without any congenital heart disease (death: 0.06%, 0.10%, and 0.13%, respectively; ESKD: 0.00%, 0.02%, and 0.02%, respectively). The risk of ESKD and death increased with severity of congenital heart disease, with the highest risk in children with hypoplastic left heart syndrome and increased in children who had surgical repair of congenital heart disease compared with those without surgical repair. CONCLUSIONS The risk of mortality and ESKD is high in children who undergo surgical repair for congenital heart disease compared to the general population.
Depressive symptoms and the general health of retired professional footballers compared with the general population in the UK: a case–control study

Objectives To determine the prevalence of depressive symptoms and general health of male ex-professional footballers compared with general population controls. Methods 572 retired professional footballers and 500 general population controls in the UK were assessed by postal questionnaire. Anxiety and depressive symptoms were assessed using the Hospital Anxiety and Depression Scale and a threshold score of ≥11 was used to indicate probable caseness. General health was ascertained using the Short Form-12 Health Survey Questionnaire quality of life (QoL) tool; self-reported comorbidities, analgesic usage and body pain; and Index of Multiple Deprivation based on postcode data. Mood was assessed using the Positive and Negative Affect Scale and sleep using the Medical Outcome Survey. Linear regression analysis was used to determine adjusted relative risk with 95% CI and adjusted for age, body mass index, comorbidities, body pain and medication usage. Results The prevalence of depressive symptoms in retired professional footballers was 5.66% compared with 5.76% in the general population and anxiety prevalence was also comparable (12.01% vs 10.29%; all p>0.05). However, footballers had lower physical and mental component scores compared with controls (p<0.01). They also reported significantly more sleep problems, more negative mood profiles and more widespread body pain (adjusted relative risk (aRR) 1.88, 95% CI 1.15 to 3.09). They also reported greater pain medication usage compared with controls (aRR 1.54, 95% CI 1.26 to 1.89). However, compared with controls, they were 26% (95% CI 15% to 37%) less likely to report comorbidities, especially heart attacks (aRR 57%, 95% CI 27% to 74%) and diabetes (aRR 61%, 95% CI 37% to 76%). Conclusions The prevalence of depressive symptoms and anxiety symptoms and probable caseness in ex-professional footballers is comparable with general population controls. However, ex-footballers reported lower health-related QoL, more widespread body pain and higher analgesic usage. Conversely, lower reporting of diabetes and heart attacks indicates potential long-term physical health benefits of professional football.