Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficient production of endotoxin depleted bioactive α-hemolysin of uropathogenic Escherichia coli

Abstract Uropathogenic E. coli (UPEC), especially associated with severe urinary tract infections (UTI) pathologies, harbors an important virulence factor known as α-hemolysin (110 kDa). Hemolytic activity of α-hemolysin (HlyA) requires modification (acylation) of two lysine residues of HlyA by HlyC, part of operon hlyCABD. Most of the previous studies had used whole operon hlyCABD and gene tolC cloning for the production of active α-hemolysin. Studies involving α-hemolysin are limited due to the cumbersome and manual method of purification for this toxin. Here, we report a simple method for production of both active and inactive recombinant α-hemolysin by cloning only hlyA and hlyC genes of operon hlyCABD. Presence of both active and inactive α-hemolysin would be advantageous for functional characterization. After translation, the yield of the purified α-hemolysin was 1 mg/200 ml. Functionality of the recombinant α-hemolysin protein was confirmed using hemolytic assay. This is the first report of the production of active and inactive recombinant α-hemolysin for functional studies.
Divergent effects of instructed and reported emotion regulation strategies on children’s memory for emotional information

ABSTRACT Distraction can reduce adults’ memory for emotion-eliciting information, whereas reappraisal can preserve or enhance it. Yet, when given instructions to use specific emotion regulation (ER) strategies, adults report using other strategies too. The consequences of non-instructed strategy use within instructed ER paradigms are rarely examined. We investigated how both instructed and non-instructed but reported strategies related to memory for emotional information in childhood. Older (N = 69; 8- to 10-year-olds; 24 girls) and younger (N = 65; 5- to 7-year-olds; 35 girls) children received instructions to use cognitive distraction, reappraisal, or do nothing (control) before and after viewing a negative emotional film clip. Children were later interviewed about what they remembered about the film, and reported the ER strategies they used during it. Memory did not vary across instructed ER strategy conditions, and reported strategies did not relate to memory differently for older and younger children. Consistent with adult work, reported cognitive distraction related to poorer memory. Different reappraisal types were reported, but only situation-focused reappraisal was linked to better memory. In sum, children’s reported cognitive distraction and reappraisal strategies related to memory for emotional information differently. Thus, ER strategies divergently relate to what children remember about their emotional experiences.
Patient organ doses from megavoltage computed tomography delivery with a helical tomotherapy unit using a general treatment planning system

Abstract The purpose of this study was to quantify actual patient organ doses from megavoltage computed tomography (MVCT) using an MVCT beam model of a helical tomotherapy unit in a general treatment planning system (TPS). Dosimetric parameters (percentage depth dose, lateral beam profile, and longitudinal beam profile) of the MVCT beam were measured using Gafchromic EBT3 films (ISP Corporation, Wayne, NJ, USA) and used for beam modeling in a Pinnacle3 TPS (Philips, Amsterdam, Netherlands); this TPS is widely used with linear accelerators. The created beam model was adjusted and validated by assessing point doses in a cylindrical phantom in static and helical beam plans with fine, normal and coarse pitches. Maximum doses delivered to important organs from MVCT delivery for five clinical cases were calculated using the created beam model. The difference (average ± one standard deviation for all evaluation points) between calculated and measured doses was −0.69 ± 1.20% in the static beam plan. In the helical beam plan, the differences were 1.83 ± 2.65%, 1.35 ± 5.94% and −0.66 ± 8.48% for fine, normal and coarse pitches, respectively. The average maximum additional dose to important organs from MVCT in clinical cases was 0.82% of the prescribed dose. In conclusion, we investigated a method for quantifying patient organ dose from MVCT delivery on helical tomotherapy using an MVCT beam model in a general TPS. This technique enables estimation of the patient-specific organ dose from MVCT delivery, without the need for additional equipment.
What matters to medical ward patients, and do we measure it? A qualitative comparison of patient priorities and current practice in quality measurement, on UK NHS medical wards

Objectives To compare the quality metrics selected for public display on medical wards to patients’ and carers’ expressed quality priorities. Methods Multimodal qualitative evaluation of general medical wards and semi-structured interviews. Setting UK tertiary National Health Service (public) hospital. Participants Fourteen patients and carers on acute medical wards and geriatric wards. Results Quality metrics on public display evaluated hand hygiene, hospital-acquired infections, nurse staffing, pressure ulcers, falls and patient feedback. The intended audience for these metrics was unclear, and the displays gave no indication as to whether performance was improving or worsening. Interviews identified three perceived key components of high-quality ward care: communication, staff attitudes and hygiene. These aligned poorly with the priorities on display. Suboptimal performance reporting had the potential to reduce patients’ trust in their medical teams. More philosophically, patients’ and carers’ ongoing experiences of care would override any other evaluation, and they felt little need for measures relating to previous performance. The display of performance reports only served to emphasise patients’ and carers’ lack of control in this inpatient setting. Conclusions There is a gap between general medical inpatients’ care priorities and the aspects of care that are publicly reported. Patients and carers do not act as ‘informed choosers’ of healthcare in the inpatient setting, and tokenistic quality measurement may have unintended consequences.
Extracranial abscopal effect induced by combining immunotherapy with brain radiotherapy in a patient with lung adenocarcinoma: A case report and literature review

An extracranial abscopal effect induced by brain radiotherapy is particularly unusual because of the brain's distinctive immune microenvironment. We report a case of an extracranial abscopal effect in a 71‐year‐old male patient with lung adenocarcinoma treated with atezolizumab and later combined with brain radiation for brain metastasis. The subsequent abscopal effect first manifested as pseudoprogression of the primary lesion in the lung before remission was confirmed. This case suggests that immunotherapy increases the chance of an abscopal effect occurring after radiation therapy for brain metastases in patients with primary tumors with low immunogenicity.
Comprehensive Researcher Achievement Model (CRAM): a framework for measuring researcher achievement, impact and influence derived from a systematic literature review of metrics and models

Objectives Effective researcher assessment is key to decisions about funding allocations, promotion and tenure. We aimed to identify what is known about methods for assessing researcher achievements, leading to a new composite assessment model. Design We systematically reviewed the literature via the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols framework. Data sources All Web of Science databases (including Core Collection, MEDLINE and BIOSIS Citation Index) to the end of 2017. Eligibility criteria (1) English language, (2) published in the last 10 years (2007–2017), (3) full text was available and (4) the article discussed an approach to the assessment of an individual researcher’s achievements. Data extraction and synthesis Articles were allocated among four pairs of reviewers for screening, with each pair randomly assigned 5% of their allocation to review concurrently against inclusion criteria. Inter-rater reliability was assessed using Cohen’s Kappa (ĸ). The ĸ statistic showed agreement ranging from moderate to almost perfect (0.4848–0.9039). Following screening, selected articles underwent full-text review and bias was assessed. Results Four hundred and seventy-eight articles were included in the final review. Established approaches developed prior to our inclusion period (eg, citations and outputs, h-index and journal impact factor) remained dominant in the literature and in practice. New bibliometric methods and models emerged in the last 10 years including: measures based on PageRank algorithms or ‘altmetric’ data, methods to apply peer judgement and techniques to assign values to publication quantity and quality. Each assessment method tended to prioritise certain aspects of achievement over others. Conclusions All metrics and models focus on an element or elements at the expense of others. A new composite design, the Comprehensive Researcher Achievement Model (CRAM), is presented, which supersedes past anachronistic models. The CRAM is modifiable to a range of applications.
MRG‐1 is required for both chromatin‐based transcriptional silencing and genomic integrity of primordial germ cells in Caenorhabditis elegans

In Caenorhabditis elegans, germline cells remain transcriptionally silenced during embryogenesis. The transcriptional silencing is achieved by two different mechanisms: One is the inhibition of RNA polymerase II in P2‐P4 cells at the establishment stage, and another is chromatin‐based silencing in two primordial germ cells (PGCs) at the maintenance stage; however, the molecular mechanism underlying chromatin‐based silencing is less understood. We investigated the role of the chromodomain protein MRG‐1, which is an essential maternal factor for germline development, in transcriptional silencing in PGCs. PGCs lacking maternal MRG‐1 showed increased levels of two histone modifications (H3K4me2 and H4K16ac), which are epigenetic markers for active transcription, and precocious activation of germline promoters. Loss of MES‐4, a H3K36 methyltransferase, also caused similar derepression of the germline genes in PGCs, suggesting that both MRG‐1 and MES‐4 function in chromatin‐based silencing in PGCs. In addition, the mrg‐1 null mutant showed abnormal chromosome structures and a decrease in homologous recombinase RAD‐51 foci in PGCs, but the mes‐4 null mutant did not show such phenotypes. Taken together, we propose that MRG‐1 has two distinct functions: chromatin‐based transcriptional silencing and preserving genomic integrity at the maintenance stage of PGCs.
Functional characterisation of two phytochelatin synthases in rice (Oryza sativa cv. Milyang 117) that respond to cadmium stress

Abstract Cadmium (Cd) is one of the most toxic heavy metals and a non‐essential element to all organisms, including plants; however, the genes involved in Cd resistance in plants remain poorly characterised. To identify Cd resistance genes in rice, we screened a rice cDNA expression library treated with CdCl2 using a yeast (Saccharomyces cerevisiae) mutant ycf1 strain (DTY167) and isolated two rice phytochelatin synthases (OsPCS5 and OsPCS15). The genes were strongly induced by Cd treatment and conferred increased resistance to Cd when expressed in the ycf1 mutant strain. In addition, the Cd concentration was twofold higher in yeast expressing OsPCS5 and OsPCS15 than in vector‐transformed yeast, and OsPCS5 and OsPCS15 localised in the cytoplasm. Arabidopsis thaliana plants overexpressing OsPCS5/‐15 paradoxically exhibited increased sensitivity to Cd, suggesting that overexpression of OsPCS5/‐15 resulted in toxicity due to excess phytochelatin production in A. thaliana. These data indicate that OsPCS5 and OsPCS15 are involved in Cd tolerance, which may be related to the relative abundances of phytochelatins synthesised by these phytochelatin synthases.
Functionalization of soft materials for cardiac repair and regeneration

Abstract Coronary artery disease is a leading cause of death in developed nations. As the disease progresses, myocardial infarction can occur leaving areas of dead tissue in the heart. To compensate, the body initiates its own repair/regenerative response in an attempt to restore function to the heart. These efforts serve as inspiration to researchers who attempt to capitalize on the natural regenerative processes to further augment repair. Thus far, researchers are exploiting these repair mechanisms in the functionalization of soft materials using a variety of growth factor-, ligand- and peptide-incorporating approaches. The goal of functionalizing soft materials is to best promote and direct the regenerative responses that are needed to restore the heart. This review summarizes the opportunities for the use of functionalized soft materials for cardiac repair and regeneration, and some of the different strategies being developed.
The Society for Pediatric Anesthesia recommendations for the use of opioids in children during the perioperative period

Opioids have long held a prominent role in the management of perioperative pain in adults and children. Published reports concerning the appropriate, and inappropriate, use of these medications in pediatric patients have appeared in various publications over the last 50 years. For this document, the Society for Pediatric Anesthesia appointed a taskforce to evaluate the available literature and formulate recommendations with respect to the most salient aspects of perioperative opioid administration in children. The recommendations are graded based on the strength of the available evidence, with consensus of the experts applied for those issues where evidence is not available. The goal of the recommendations was to address the most important issues concerning opioid administration to children after surgery, including appropriate assessment of pain, monitoring of patients on opioid therapy, opioid dosing considerations, side effects of opioid treatment, strategies for opioid delivery, and assessment of analgesic efficacy. Regular updates are planned with a re‐release of guidelines every 2 years.
Reduced Aortic Distensibility is Associated With Higher Aorto‐Carotid Wave Transmission and Central Aortic Systolic Pressure in Young Adults After Coarctation Repair

Background The long‐term prognosis of patients with repaired aortic coarctation is characterized by high rates of cardiovascular and cerebrovascular disease related to hypertension, the basis of which remains unclear. To define potential underlying mechanisms, we investigated aortic and carotid arterial biomechanics and wave dynamics, and determinants of aortic systolic blood pressure, in young adults after coarctation repair. Methods and Results Aortic arch and carotid biomechanics, wave intensity and wave power, and central aortic blood pressure, were derived from echocardiography and brachial blood pressure in 43 young adults after coarctation repair and 42 controls. Coarctation subjects had higher brachial and central systolic blood pressure (P=0.04), while aortic compliance was lower and characteristic impedance (Zc) higher. Although carotid intima‐media thickness was higher (P<0.001), carotid biomechanics were no different. Carotid forward compression wave power was higher and was negatively correlated with aortic compliance (R 2=0.42, P<0.001) and distensibility (R 2=0.37, P=0.001) in coarctation subjects. Aortic wave power and wave reflection indices were no different in control and coarctation patients, but coarctation patients with elevated aortic Zc had greater aorto‐carotid transmission of forward compression wave power (P=0.006). Aortic distensibility was the only independent predictor of central aortic systolic blood pressure on multivariable analysis. Conclusions Young adults following coarctation repair had a less compliant aorta, but no change in carotid biomechanics. Reduced aortic distensibility was related to greater transmission of aortic forward wave energy into the carotid artery and higher central aortic systolic blood pressure. These findings suggest that reduced aortic distensibility may contribute to later cardiovascular and cerebrovascular disease after coarctation repair.
Metabolic profiling of elite athletes with different cardiovascular demand

Intensive exercise of elite athletes can lead to physiological alterations in the cardiovascular system in response to increased stroke volume and blood pressure, known collectively as cardiovascular demand (CD). This study aimed to compare metabolic differences in elite athletes with high vs low/moderate CD and to reveal their underlying metabolic pathways as potential biomarker signatures for assessing health, performance, and recovery of elite athletes. Metabolic profiling of serum samples from 495 elite athletes from different sport disciplines (118 high CD and 377 low/moderate CD athletes) was conducted using non‐targeted metabolomics‐based mass spectroscopy combined with ultra‐high‐performance liquid chromatography. Results show that DAGs containing arachidonic were enriched in high CD together with branched‐chain amino acids, plasminogens, phosphatidylcholines, and phosphatidylethanolamines, potentially indicating increased risk of cardiovascular disease in the high CD group. Gamma‐glutamyl amino acids and glutathione metabolism were increased in low/moderate CD group, suggesting more efficient oxidative stress scavenging mechanisms than the high CD group. This first most comprehensive metabolic profiling of elite athletes provides an evidence that athletes with different CD show a unique metabolic signature that reflects energy generation and oxidative stress and potentially places the high CD group at a higher risk of cardiovascular disease. Further studies are warranted for confirmation and validation of findings in other sport groups in light of potential confounders related to limited available information about participants.
3-Trifluoromethylpyrazolones derived nucleosides: Synthesis and antiviral evaluation

Abstract Dengue (DENV) viral infection is a global public health problem that infrequently develops life threatening diseases such as dengue hemorrhagic fever (DFS) and dengue shock syndrome (DSS). Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human corona virus with 38% fatality rate of infected patients. A series of 4-arylhydrazono-5-trifluoromethyl-pyrazolones, their ribofuranosyl, and 5′-deoxyribofuranosyl nucleosides were synthesized, geometry optimized using Density functional theory (DFT), and evaluated for their antiviral activity. 2-Nitrophenylhydrazonopyra-zolone derivative 5 showed significant activity against MERS-CoV (EC50 = 4.6 μM). The nucleoside analog 8 showed moderate activity against DENV-2 (EC50 = 10 μM), while the activity was abolished with the corresponding 5′-deoxyribonucleoside analogs. The identified hits in this study set this category of compounds for further future optimizations.
Are neighborhood characteristics associated with sedentary behavior in adolescents? A systematic review

ABSTRACT Sedentary behavior (SB) has emerged as a potential risk factor for chronic diseases. SB includes activities requiring low energy expenditure (≤1.5 metabolic equivalents) performed in a sitting or reclining posture. Our study aimed to gather evidence on the association between SB outcomes in adolescents (10–19 years) and neighborhood characteristics. This systematic review (PROSPERO registration number: CRD42018076877) examined studies indexed in PubMed Central®, LILACS, ScienceDirect, and SPORTDiscus databases. Sixteen articles were included. Insecurity during daytime hours, crime incidence, physical and social disorders, a higher neighborhood socioeconomic level, and time spent with peers were associated with higher levels of SB. Traffic, availability of a favorable environment for physical activity, and higher residential density were associated with lower levels of SB. Despite great variability in the SB cutoff points and methodology used for evaluating SB and neighborhood characteristics among studies, the evidence suggests that adolescent SB might be influenced by neighborhood characteristics.
JCS 2018 Guideline on Diagnosis and Treatment of Acute Coronary Syndrome.

J-STAGE Advance Publication released online March 29, 2019 Mailing address: Scientific Committee of the Japanese Circulation Society, 18F Imperial Hotel Tower, 1-1-1 Uchisaiwai-cho, Chiyoda-ku, Tokyo 100-0011, Japan. E-mail: meeting@j-circ.or. jp This document is an English version of JCS 2018 Guideline on Diagnosis and Treatment of Acute Coronary Syndrome reported at the Japanese Circulation Society Joint Working Groups performed in 2018. (Website: http://www.j-circ.or.jp/guideline/pdf/JCS2018_ kimura.pdf). *Chairperson. Refer to Appendix 1 for the details of members. Joint Working Groups: The Japanese Circulation Society, the Japanese Association for Thoracic Surgery, the Japanese Association of Cardiac Rehabilitation, the Japanese Association of Cardiovascular Intervention and Therapeutics, the Japanese College of Cardiology, the Japanese Coronary Association, the Japanese Heart Rhythm Society, the Japanese Society for Cardiovascular Surgery, the Japanese Society of Intensive Care Medicine ISSN-1346-9843 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or. jp JCS 2018 Guideline on Diagnosis and Treatment of Acute Coronary Syndrome
IPS-1 polymorphisms in regulating interferon response in HBV infection.

Single nucleotide polymorphisms (SNP) influence the outcome of antiviral therapy in chronic hepatitis B patients. Interferon β promoter stimulator 1 polymorphisms (IPS-1) regulate interferon (IFN) mediated viral clearance in hepatitis B virus (HBV) infection. In our study, HepG2 and HepG2.2. 15 were transfected with different SNP genotype expression vectors of IPS-1 (wild-type, rs17857295, rs7262903 and rs7269320). The production of IPS-1 and IFN were evaluated in these transfected cells. IPS-1 in the HepG2.2. 15 cells transfected with rs17857295 or rs7262903 was 37% or 31% lower than that with wild-type transfection (p < 0.001). IFN-β in rs17857295 or rs7262903 transfected HepG2.2. 15 cells was 5.4 or 3.7 fold higher than that of wild-type transfection (p < 0.0001). IPS-1 in rs7269320 SNP transfected HepG2.2. 15 cells was 40% lower than that of wild-type transfection (p < 0.0001); no significantly different IFN-β was observed between rs7269320 SNP and wild-type transfections. IFN-β expression was > 2 fold higher in rs17857295 transfected HepG2.2. 15 cells than HepG2 cells (p < 0.001). The data suggests that host HBV viral clearance is stronger in IPS-1 rs17857295 or rs7262903 SNP genotype patients than wild-type patients. Relatively weak inducible IFN-β production in HBV infected patients with IPS-1 rs7269320 SNP or wild-type may contribute to chronic virus infection.