Miracle-dz/UniFAR-FTUs huggingface dataset:
Individualized Pharmacokinetic Dosing of Vancomycin Reduces Time to Therapeutic Trough Concentrations in Critically Ill Patients

Dosing vancomycin in critically ill patients often results in subtherapeutic and supratherapeutic trough concentrations. In this retrospective study, we compared the time to goal trough attainment and incidence of acute kidney injury in intensive care unit (ICU) patients whose vancomycin was dosed by a pharmacy pharmacokinetic (PK) dosing and monitoring service to the standard of care. Three‐hundred fifty adult ICU patients at a Level 1 trauma, teaching hospital who received vancomycin for >24 hours from February 1, 2016, to November 30, 2016, were screened. Patients were included in the PK group if consecutive serum concentrations were used to calculate individualized PK and determine a dosing regimen. Patients who were dosed using troughs only were then matched 1‐to‐1 to the PK group by date of vancomycin initiation and included in the traditional group. Fifty patients were included in each group. Baseline characteristics were similar, except the PK group had more patients under the care of the neuromedical ICU service (42% vs 18%; P = .02) and fewer patients with a corrected creatinine clearance <30 mL/min/1.73 m2 (22% vs 46%; P = .02). Attainment of goal trough concentrations for the PK and traditional groups were 84.4% and 29.4% by 48 hours (P = .0001), 88.4% and 60.7% by 72 hours (P = .009), and 92.9% and 77.8% by 96 hours (P = .1), respectively. Incidence of acute kidney injury between the PK and traditional groups was not statistically significant (8.3% vs 14%; P = .5). Utilization of individualized pharmacokinetic dosing of vancomycin in critically ill patients resulted in faster goal trough attainment without an increase in nephrotoxicity.
Lung function tests to monitor respiratory disease in preschool children

Pulmonary function tests are routinely used in the diagnosis and follow-up of respiratory diseases. In preschool children assessment and evaluation of lung function has always been challenging but improved techniques that require only minimal collaboration allowed obtaining reliable and useful results even in this group of patients. In this review we will describe the different techniques used in clinical practice to measure lung function in preschool children. (www.actabiomedica.it)
Patent ductus arteriosus in preterm infants born before 30 weeks’ gestation: high rate of spontaneous closure after hospital discharge

Abstract Aim The aim of this study was to determine the spontaneous closure rate of patent ductus arteriosus at a 2-year follow-up, following failed medical therapy and beyond initial hospital discharge, and to evaluate in-hospital spontaneous or pharmacological closure rates. Materials and methods A retrospective evaluation was conducted in a cohort of preterm infants admitted to the Neonatal ICU of Ancona between January, 2004 and June, 2013. Inclusion criteria were gestational age between 24+0 and 29+6 weeks or birth weight <1250 g; admission within 48 hours from birth; and discharge alive from hospital. All infants received routine heart ultrasound between 48 and 72 hours of life. Haemodynamically significant patent ductus arteriosus was defined as a duct diameter >1.5 mm, a left atrium-to-aorta ratio >1.4, and/or reversal of end-diastolic flow in the aorta >30% of the anterograde. First-line treatment was intravenous ibuprofen. Intravenous indomethacin was used if ibuprofen failed. Surgical ligation was considered in haemodynamically significant patent ductus arteriosus after medical treatment. Results A total of 593 infants met the inclusion criteria, and patent ductus arteriosus was diagnosed in 317 (53.4%). Among them, 283 (89.3%) infants had haemodynamically significant patent ductus arteriosus, with pharmacological closure achieved in 228 (80.6%) infants and surgical ligation performed in 20 (7.1%). Follow-up at 24 months was available for 39 (81.3%) of 48 infants with patent ductus arteriosus at the hospital discharge: 36 (92.3%) underwent spontaneous closure, two (5.1%) underwent surgical ligation, and one (2.6%) had a patent ductus arteriosus. Discussion A significant number of patent ductus arteriosus that fail pharmacological closure undergo spontaneous closure by the age of 2 years. This information should be taken into account when considering surgery or additional attempts of pharmacological closure.
Horizontal Transfer of Symbiosis Genes within and Between Rhizobial Genera: Occurrence and Importance

Rhizobial symbiosis genes are often carried on symbiotic islands or plasmids that can be transferred (horizontal transfer) between different bacterial species. Symbiosis genes involved in horizontal transfer have different phylogenies with respect to the core genome of their ‘host’. Here, the literature on legume–rhizobium symbioses in field soils was reviewed, and cases of phylogenetic incongruence between rhizobium core and symbiosis genes were collated. The occurrence and importance of horizontal transfer of rhizobial symbiosis genes within and between bacterial genera were assessed. Horizontal transfer of symbiosis genes between rhizobial strains is of common occurrence, is widespread geographically, is not restricted to specific rhizobial genera, and occurs within and between rhizobial genera. The transfer of symbiosis genes to bacteria adapted to local soil conditions can allow these bacteria to become rhizobial symbionts of previously incompatible legumes growing in these soils. This, in turn, will have consequences for the growth, life history, and biogeography of the legume species involved, which provides a critical ecological link connecting the horizontal transfer of symbiosis genes between rhizobial bacteria in the soil to the above-ground floral biodiversity and vegetation community structure.
Failure to Replicate the Effects of the High-Probability Instructional Sequence on Feeding in Children With Autism and Food Selectivity

Behavioral intervention has positive effects on feeding problems of children with autism and food selectivity (FS), and researchers have evaluated a variety of specific behavioral interventions. Confidence in the effects of some specific interventions on feeding such as the high-probability instructional sequence (HPS) is limited by a lack of replication. Therefore, we assessed the generality of the HPS by replicating the intervention in children with autism and FS. Contrary to prior research, the HPS did not improve feeding responses for three consecutive children enrolled in the study. We discuss the results in relation to publishing failures to replicate without experimental control in applied behavior analysis research.
Concordance between Goals of Care and Treatment Decisions for Persons with Dementia.

BACKGROUND Nursing home (NH) residents with dementia experience high rates of intensive treatment near the end of life. Limited research examines whether treatment is concordant with goals of care (GOC). OBJECTIVES We analyzed data from the GOC trial to describe family decision makers' preferred GOC and perceptions of goal-concordant care for NH residents with late-stage dementia We compared subsequent treatment orders when families chose a primary goal of comfort versus other goals. DESIGN We performed a secondary analysis of data from baseline and 9-month family decision-maker interviews and chart reviews. SETTING AND PARTICIPANTS A total of 302 dyads of NH residents and family decision makers in 22 North Carolina NHs were enrolled. MEASUREMENTS In baseline and follow-up interviews, families reported on their and NH staff's primary GOC, and perceived prognosis and goal-concordant care. Chart reviews provided data on treatment orders, hospital transfers, and hospice, which were compared after selection of a primary goal of comfort versus other goals. RESULTS Family chose comfort as the primary goal for 66% of residents at baseline, and for nearly 80% by 9 months or death. At baseline, 49% perceived concordance with NH staff on the primary goal, and 69% at follow-up. In multivariate models, choice of comfort as the primary goal, versus other goals, was associated with half as many hospital transfers (0.11 vs. 0.25/90 person-days, confidence interval [-0.2 to -0.01]), but not with hospice or treatment orders. CONCLUSIONS Most families chose comfort as the primary GOC. Further research is needed to translate this preference into comfort-focused treatment plans for late-stage dementia. Clinicaltrials.gov : NCT01565642 (3/26/12).
Biological rhythms, chronodisruption and chrono-enhancement: The role of physical activity as synchronizer in correcting steroids circadian rhythm in metabolic dysfunctions and cancer

ABSTRACT Rhythms can be observed at all levels of the biologic integration in humans. The observation that a biological or physiological variable shows a circadian rhythm can be explained by several multifactorial systems including external (exogenous), internal (endogenous) and psychobiological (lifestyle) mechanisms. Our body clock can be synchronized with the environment by external factors, called “synchronizers”, i.e. the light–dark cycle, but it is also negatively influenced by some pathological conditions or factors, called “chronodisruptors,” i.e. aging or low physical activity (PA). The desynchronization of a 24-h rhythm in a chronic manner has been recently defined “chronodisruption” or “circadian disruption. ” A very large number of hormonal variables, such as adrenal and gonadal stress steroids, are governed by circadian rhythmicity. Such hormones, in normal conditions, show a peak in the first part of the day, while their typical diurnal fluctuations are totally out of sync in subjects affected by cancer or metabolic diseases, such as obesity, diabetes and metabolic syndrome. In general, a flatter slope with altered peaks in cortisol and testosterone circadian rhythms has been observed in pathological individuals. PA, specifically chronic exercise, seems to play a key role as synchronizer for the whole circadian system in such pathologies even if specific data on steroids circadian pattern are still sparse and contradictory. Recently, it has been proposed that low-intensity chronic PA could be an effective intervention to decrease morning cortisol levels in pathological subjects. The standardization of all confounding factors is needed to reach more clear evidence-based results.
Sodium intake and blood pressure in children and adolescents: a systematic review and meta-analysis of experimental and observational studies.

Background High sodium intake is a cause of elevated blood pressure in adults. In children and adolescents, less evidence is available and findings are equivocal. We systematically reviewed the evidence from experimental and observational studies on the association between sodium intake and blood pressure in children and adolescents. Methods A systematic search of the Medline, Embase, CINAHL and CENTRAL databases up to March 2017 was conducted and supplemented by a manual search of bibliographies and unpublished studies. Experimental and observational studies involving children or adolescents between 0 and 18 years of age were included. Random-effects meta-analyses were performed by pooling data across all studies, separately for experimental and observational studies, and restricting to studies with sodium intake and blood pressure measurement methods of high quality. Subgroup meta-analyses, sensitivity analyses and meta-regressions were conducted to investigate sources of heterogeneity and confounding. The dose-response relationship was also investigated. Results Of the 6572 publications identified, 85 studies (14 experimental; 71 observational, including 60 cross-sectional, 6 cohort and 5 case-control studies) with 58 531 participants were included. In experimental studies, sodium reduction interventions decreased systolic blood pressure by 0.6 mm Hg [95% confidence interval (CI): 0.5, 0.8] and diastolic blood pressure by 1.2 mm Hg (95% CI: 0.4, 1.9). The meta-analysis of 18 experimental and observational studies (including 3406 participants) with sodium intake and blood pressure measurement methods of high quality showed that, for every additional gram of sodium intake per day, systolic blood pressure increased by 0.8 mm Hg (95% CI: 0.4, 1.3) and diastolic blood pressure by 0.7 mm Hg (95% CI: 0.0, 1.4). The association was stronger among children with overweight and with low potassium intake. A quasi-linear relationship was found between sodium intake and blood pressure. Conclusions Sodium intake is positively associated with blood pressure in children and adolescents, with consistent findings in experimental and observational studies. Since blood pressure tracks across the life course, our findings support the reduction of sodium intake during childhood and adolescence to lower blood pressure and prevent the development of hypertension.
Unmasking the impact of Rictor in cancer: novel insights of mTORC2 complex

Genomic alterations affecting components of the mechanistic target of rapamycin (mTOR) pathway are found rather frequently in cancers, suggesting that aberrant pathway activity is implicated in oncogenesis of different tumor types. mTOR functions as the core catalytic kinase of two distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which control numerous vital cellular processes. There is growing evidence indicating that Rictor, an essential subunit of the mTORC2 complex, is inappropriately overexpressed across numerous cancer types and this is associated with poor survival. To date, the candidate mechanisms responsible for aberrant Rictor expression described in cancer are two: i) gene amplification and ii) epigenetic regulation, mainly by microRNAs. Moreover, different mTOR-independent Rictor-containing complexes with oncogenic role have been documented, revealing alternative routes of Rictor-driven tumorigenesis, but simultaneously, paving the way for identifying novel biomarkers and therapeutic targets. Here, we review the main preclinical and clinical data regarding the role of Rictor in carcinogenesis and metastatic behavior as well as the potentiality of its alteration as a target.
Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults and adolescents—a life-threatening disease: analysis of 133 cases from a single center

ABSTRACT Objectives: Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis is the most common type of infection-associated HLH. Previous studies were focused on pediatric EBV-HLH patients, therefore there lack of adult data. Method: We performed a retrospective analysis of 133 EBV-HLH patients (≥14 years old) in Beijing Friendship Hospital from March 2009 to April 2016 to evaluate the clinical manifestation and the effects and prognosis of existing regimens of EBV-HLH in adult and adolescents. Results: Of these patients, 91 male and 42 female cases had a median age of 26 (14–77) years. EBV-DNA load on admission was at a median of 6.6E + 05 IU/ml. The one-year mortality of these patients was 78%. 112 patients received the HLH-94/04 regimen as the initial treatment, 52 patients (46.43%) had response. Of the 6 patients who received the L-DEP regimen as the initial treatment, 5 patients (83.33%) had response. The rest 15 patients received initial treatment without etoposide, 5 cases achieved PR. 69 refractory or relapsed patients received DEP or L-DEP regimen, 55 (79.71%) cases had response. In addition, who received the L-DEP regimen, with the overall response rate significantly higher than the DEP regimen (88.37% VS 65.38%, P = 0.031). 36 out of 133 EBV-HLH patients eventually received allo-HSCT, with the overall survival rate of 52.78%. In summary, EBV-HLH is a highly lethal disease. Conclusion: DEP/L-DEP was a good salvage treatment. L-DEP might be a more effective first-line initial regimen than HLH-94/04 regimen for EBV-HLH. Finally, allo-HSCT is an effective radical treatment for EBV-HLH.
Assessment of a Density-Based Action Threshold for Suppression of Sugarcane Aphids, (Hemiptera: Aphididae), in the Southern High Plains

Abstract In the High Plains, sugarcane aphid, Melanaphis sacchari Zehntner (Hemiptera: Aphididae), colonize grain sorghum, Sorghum bicolor (L) Moench (Cyperales: Poaceae), when it is in reproductive stages and aphid populations increase rapidly. Sugarcane aphid management recommendations based on aphid densities have been implemented in southern United States, but have not been assessed in the High Plains. Therefore, the goal of this work was to validate whether these guidelines can provide effective suppression of the aphids and improve yield. In a 2-y field experiment, sorghum susceptible (DKS44-20) and resistant (DKS37-07) to sugarcane aphids, with and without insecticide (clothianidin) seed treatments, was exposed to natural aphid infestations and treated with a foliar insecticide (flupyradifurone) once sugarcane aphid densities exceeded 50 per leaf. Further, to assess the effects of these tactics on sorghum yield, data were collected from plots that were not treated at the threshold. In both years, foliar insecticide applied at the density-based threshold decreased aphid numbers across sorghum hybrids with and without seed treatments and aphid densities remained below threshold for the remainder of the season. Yield of sorghum depended on sugarcane aphid pressure—when their densities were high (2016), the resistant hybrid with and without the foliar spray outperformed the unsprayed susceptible hybrid, while the susceptible hybrid had higher yields than resistant hybrid when sugarcane aphid pressure was low (2017). Outcomes of this work support the notion that a well-timed foliar application can alleviated losses in yield in sorghum in the Texas Panhandle and potentially other regions of the High Plains.
Implementing infection prevention practices across European hospitals: an in-depth qualitative assessment

Objective The Prevention of Hospital Infections by Intervention and Training (PROHIBIT) project included a cluster-randomised, stepped wedge, controlled study to evaluate multiple strategies to prevent catheter-related bloodstream infection. We report an in-depth investigation of the main barriers, facilitators and contextual factors relevant to successfully implementing these strategies in European acute care hospitals. Methods Qualitative comparative case study in 6 of the 14 European PROHIBIT hospitals. Data were collected through interviews with key stakeholders and ethnographic observations conducted during 2-day site visits, before and 1 year into the PROHIBIT intervention. Qualitative measures of implementation success included intervention fidelity, adaptation to local context and satisfaction with the intervention programme. Results Three meta-themes emerged related to implementation success: ‘implementation agendas’, ‘resources’ and ‘boundary-spanning’. Hospitals established unique implementation agendas that, while not always aligned with the project goals, shaped subsequent actions. Successful implementation required having sufficient human and material resources and dedicated change agents who helped make the intervention an institutional priority. The salary provided for a dedicated study nurse was a key facilitator. Personal commitment of influential individuals and boundary spanners helped overcome resource restrictions and intrainstitutional segregation. Conclusion This qualitative study revealed patterns across cases that were associated with successful implementation. Consideration of the intervention–context relation was indispensable to understanding the observed outcomes.
Low recurrence rate of head and neck basal cell carcinoma treated with Mohs micrographic surgery: A retrospective study of 1021 cases

Mohs micrographic surgery (MMS) is the treatment of choice for high‐risk primary basal cell carcinoma (BCC) and recurrent BCC of the head and neck, showing fewer recurrences compared with surgical excision (SE). The objectives of this study were to determine the recurrence rate of head and neck BCC after MMS and to develop a prediction model with significant risk factors for recurrence.
Impact of the introduction of a universal childhood influenza vaccination programme on influenza-related admissions to paediatric intensive care units in England

Introduction A universal childhood influenza vaccination programme was introduced in the UK in September 2013. We examine the impact of the gradual introduction of this programme on influenza-related paediatric intensive care unit (PICU) admission rates in England. Methods We extracted data on all influenza-related admissions to PICUs in England in resident children aged 0–15 years old between October 2003 and March 2017 from the Paediatric Intensive Care Audit Network (PICANet) database. We estimated influenza-associated PICU admission rates per 100 000 children by age group, sex and winter season (October to March), and used Poisson regression models to estimate incidence rate ratios (IRRs) in the winter seasons since the introduction of universal childhood vaccination compared with the two winters before the introduction of the programme (2011–2013). Results We identified 929 influenza-related PICU admissions among 873 children. 48.3% of admissions were among children aged less than 2 years old. The influenza-associated PICU admission rate was 1.32 per 100 000 children (95% CI 1.23 to 1.40). We identified a significant increase in influenza PICU admissions in the winters following the introduction of the universal childhood vaccination programme compared with the winters of 2010/2011–2012/2013 among children aged <5 years old: IRR 1.58 (1.05, 2.37) in children <1 year, 2.71 (1.43, 5.17) in 1 year-olds and 1.98 (1.18, 3.31) in children 2–4 years old. No significant difference was found among children aged 5–15 years. Conclusion The universal childhood influenza vaccination has not yet reduced the influenza-associated burden on PICUs in England during its early phase of introduction. Monitoring of influenza PICU admission rates needs to continue in England to assess the long-term impact of universal paediatric influenza vaccination. Linkage between PICANet and national infection surveillance databases would better enable such monitoring.
Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line

The SK-BR-3 cell line is one of the most important models for HER2+ breast cancers, which affect one in five breast cancer patients. SK-BR-3 is known to be highly rearranged although much of the variation is in complex and repetitive regions that may be underreported. Addressing this, we sequenced SK-BR-3 using long-read single molecule sequencing from Pacific Biosciences, and develop one of the most detailed maps of structural variations (SVs) in a cancer genome available with nearly 20,000 variants present, most of which were missed by prior efforts. Surrounding the important HER2 locus, we discover a complex sequence of nested duplications and translocations, suggesting a punctuated progression. Full-length transcriptome sequencing further revealed several novel gene fusions within the nested genomic variants. Combining long-read genome and transcriptome sequencing enables an in-depth analysis of how SVs disrupt the transcriptome and sheds new light on the complexity of cancer progression.