Miracle-dz/UniFAR-FTUs huggingface dataset:
Reducing the radiation exposure from CT scanning in children with shunts: a nationwide survey and a departmental CT protocol

Abstract Introduction: Low dose ionising radiation such as from CT scans carries a low but cumulative risk of cancer and children are particularly sensitive. Children with VP Shunts often undergo multiple CT scans. We developed a CT protocol with reduced radiation for paediatric patients with shunts and compared it with the current practice in the other neurosurgical units in the UK and ROI by conducting a nationwide survey. Methods: An email questionnaire was send to the superintendent radiographer in every Neurosurgical unit in the UK and the ROI. Results: The response rate was 70%. Only 5 (19%) of the responding units used a dedicated CT shunt protocol with reduced radiation. Radiation was reduced by lowering the tube current. In comparison, our protocol uses a combination of less tube current and fewer slices. This reduced the radiation exposure of a CT head significantly with sufficient image quality to make a diagnosis. Conclusion: Radiation from CT for paediatric shunt patients scans can and should be reduced. This can be achieved by using reduced radiation protocols. A national paediatric CT shunt protocol could lead to significant reduction in effective radiation dose.
A Perspective on Rabies in the Middle East—Beyond Neglect

Rabies is a neglected but preventable viral zoonosis that poses a substantial threat to public health. In this regard, a global program has been initiated for the elimination of human rabies caused by rabid dogs through the mass vaccination of canine populations. Geographic areas vary greatly towards attainment of this objective. For example, while dog-mediated and wildlife rabies have been largely controlled in major parts of the Americas and Western Europe, the Middle East still grapples with human rabies transmitted by unvaccinated dogs and cats. Rabies prevention and control in the Middle East is quite difficult because the region is transcontinental, encompassing portions of Africa, Asia, and Europe, while consisting of politically, culturally, and economically diverse countries that are often subject to war and unrest. Consequently, one over-riding dilemma is the misinformation or complete lack of rabies surveillance data from this area. This communication is an attempt to provide an overview of rabies in the Middle East, as a cohesive approach for the honing of disease management in each area, based on data compiled from multiple sources. In addition, the related regional transboundary movement of rabies was investigated through phylogenetic studies of available viral gene sequences. Thereafter, the epidemiological status of rabies was assessed for the region. Finally, localities were classified first by the Stepwise Approach towards Rabies Elimination framework and then categorized into four different groups based on management theme: “rabies free”; owned dog and domestic animal vaccination; community dog vaccination; and wildlife vaccination. The classification system proposed herein may serve as a baseline for future efforts. This is especially important due to the severe lack of rabies information available for the Middle East as a whole and a need for a comprehensive program focusing on the entirety of the region in light of renewed international commitment towards canine rabies elimination.
Use of an E2SFCA Method to Measure and Analyse Spatial Accessibility to Medical Services for Elderly People in Wuhan, China

Current studies on measuring the accessibility of medical services for the elderly (AMSE) have ignored the potential competition among supply and demand and the distance decay laws. Hence, an enhanced two-step floating catchment area (E2SFCA) method (i.e., the road network-based Gaussian 2SFCA method) is proposed to calculate AMSE scores after considering different types of roads, including urban rail transit, freeways, major roads, minor roads and rural roads. Based on the first National Geographic Conditions Monitoring (NGCM) data, this study took Wuhan, China, as a case study and assessed the variation of AMSE using two different threshold times (i.e., Platinum Ten and Golden Hour). Next, global (i.e., sensitivity and hot spot analysis) and local analyses (i.e., three regional area internal comparisons) of AMSE scores were conducted to accurately identify details in the variation of spatial accessibility. It was observed that the E2SFCA method could be easily applied to measure AMSE. The results showed that 48.63% of the elderly population in Wuhan had a higher or the highest level of medical accessibility in “Platinum Ten”, while 72.97% had a higher or the highest level in the “Golden Hour”, and hot spots of AMSE scores were located in central urban areas and presented an enclosure structure using both threshold travel times, which could provide guidance to governments or planners on issues of spatial planning and identifying elderly medical services shortage areas.
Selumetinib Activity in Thyroid Cancer Cells: Modulation of Sodium Iodide Symporter and Associated miRNAs

Background: The MEK (mitogen-activated protein kinase)–inhibitor selumetinib led to increased radioiodine uptake and retention in a subgroup of patients suffering from radioiodine refractory differentiated thyroid cancer (RR-DTC). We aimed to analyse the effect of selumetinib on the expression of sodium iodide symporter (NIS; SLC5A5) and associated miRNAs in thyroid cancer cells. Methods: Cytotoxicity was assessed by viability assay in TPC1, BCPAP, C643 and 8505C thyroid cancer cell lines. NIS, hsa-let-7f-5p, hsa-miR-146b-5p, and hsa-miR-146b-3p expression was determined by quantitative RT-PCR. NIS protein was detected by Western blot. Radioiodine uptake was performed with a Gamma counter. Results: Selumetinib caused a significant reduction of cell viability in all thyroid cancer cell lines. NIS transcript was restored by selumetinib in all cell lines. Its protein level was found up-regulated in TPC1 and BCPAP cells and down-regulated in C643 and 8505C cells after treatment with selumetinib. Treatment with selumetinib caused a down-regulation of hsa-let-7f-5p, hsa-miR-146b-5p and hsa-miR-146b-3p in TPC1 and BCPAP cells. In 8505C cells, a stable or down-regulated hsa-miR-146b-5p was detected after 1h and 48h of treatment. C643 cells showed stable or up-regulated hsa-let-7f-5p, hsa-miR-146b-5p and hsa-miR-146b-3p. Selumetinib treatment caused an increase of radioiodine uptake, which was significant in TPC1 cells. Conclusions: The study shows for the first time that selumetinib restores NIS by the inhibition of its related targeting miRNAs. Further studies are needed to clarify the exact mechanism activated by hsa-miR-146b-5p, hsa-miR-146b-3p and hsa-let7f-5p to stabilise NIS. Restoration of NIS could represent a milestone for the treatment of advanced RR-DTC.
Dissimilarity Metric Based on Local Neighboring Information and Genetic Programming for Data Dissemination in Vehicular Ad Hoc Networks (VANETs)

This paper presents a novel dissimilarity metric based on local neighboring information and a genetic programming approach for efficient data dissemination in Vehicular Ad Hoc Networks (VANETs). The primary aim of the dissimilarity metric is to replace the Euclidean distance in probabilistic data dissemination schemes, which use the relative Euclidean distance among vehicles to determine the retransmission probability. The novel dissimilarity metric is obtained by applying a metaheuristic genetic programming approach, which provides a formula that maximizes the Pearson Correlation Coefficient between the novel dissimilarity metric and the Euclidean metric in several representative VANET scenarios. Findings show that the obtained dissimilarity metric correlates with the Euclidean distance up to 8.9% better than classical dissimilarity metrics. Moreover, the obtained dissimilarity metric is evaluated when used in well-known data dissemination schemes, such as p-persistence, polynomial and irresponsible algorithm. The obtained dissimilarity metric achieves significant improvements in terms of reachability in comparison with the classical dissimilarity metrics and the Euclidean metric-based schemes in the studied VANET urban scenarios.
Effect of resistance training with different frequencies and subsequent detraining on muscle mass and appendicular lean soft tissue, IGF-1, and testosterone in older women

Abstract Objective: To analyse the effect of resistance training (RT) frequency on muscle mass, appendicular lean soft tissue, insulin-like growth factor 1 (IGF-1), testosterone, and their changes with detraining in older women. Methods: Forty-five physically independent older women (≥ 60 years) were randomly assigned to perform RT either two (G2X, n = 21) or three times/week (G3X, n = 24), during 12 weeks (8 exercises, 1 set of 10–15 repetition maximum). Muscle mass and appendicular lean soft tissue, IGF-1, testosterone, and dietary intake were measured at pre-training, post-training, and after detraining (12 weeks). Results: Muscle mass and appendicular lean soft tissue significantly increased post-training (G2X = +5.5% and G3X = +5.8%, P < .0001) with no differences between groups, and gains were retained after detraining (G2X = 100% and G3X = 99%, P < .0001). IGF-1 and dietary intake did not change for the groups during the study. Testosterone did not change post-training but significantly decreased after detraining (G2X = −21% and G3X = −50%, P < .0001). Conclusion: We conclude that lower RT frequency is as effective as higher frequency to improve muscle mass and appendicular lean soft tissue, and to maintain testosterone and IGF-1. Additionally, detraining may reduce testosterone regardless of RT frequency. These results are specifically for community-dwelling older women and may not be generalized to other populations.
Mean Platelet Volume and Platelet Distribution Width in Patients With Obstructive Sleep Apnea Syndrome and Concurrent Chronic Obstructive Pulmonary Disease

Evidence suggests that there is platelet activation in obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD). Our objective is to evaluate mean platelet volume (MPV) and platelet distribution width (PDW) in patients with overlap syndrome (OS), that is, concurrent COPD with OSAS. Mean platelet volume and PDW were assessed in consecutive patients who had undergone polysomnography and pulmonary function testing. They were divided into the following groups: controls (apnea–hypopnea index [AHI] <5/hour, and forced expiratory volume in 1st second [FEV1]/forced vital capacity [FVC] >70%), OSAS group (AHI ≥5/hour and FEV1/FVC >70%), and OS group (AHI ≥5/hour and FEV1/FVC <70%). A total of 485 patients (360 males and 125 females) were included. Mean platelet volume in controls was lower compared with the other groups: 10 ± 0.9 fL for controls versus 10.3 ± 1.2 fL for OSAS (P = .006), versus 10.7 ± 1 fL for OS (P < .001). Additionally, MPV was higher in OS group than OSAS: 10.7 ± 1 fL versus 10.3 ± 1.2 fL, respectively (P = .002). Platelet distribution width was lower in controls compared with the other groups: 12.9 ± 2 fL for controls versus 13.6 ± 1.9 fL for OSAS (P = .007), versus 13.8 ± 2.3 fL for OS (P = .008), while there was no difference between OS and OSAS groups. Mean platelet volume and PDW are increased in patients with OS compared with healthy controls, with respiratory function being the major contributor in platelet activation in this series.
Lefamulin: Review of a Promising Novel Pleuromutilin Antibiotic

The emergence and spread of antimicrobial resistance have led to a global public health emergency requiring development of new antimicrobial classes. Lefamulin (formally BC‐3781) is a novel pleuromutilin antibiotic currently undergoing Food and Drug Administration review for community‐acquired bacterial pneumonia (CABP) as intravenous (IV) and oral (PO) formulations. Although pleuromutilin antibiotics were first developed in the 1950s, lefamulin is the first to be used for systemic treatment of bacterial infections in humans. Lefamulin exhibits a unique mechanism of action through inhibition of protein synthesis by binding to the peptidyl transferase center of the 50S bacterial ribosome, thus preventing the binding of transfer RNA for peptide transfer. Lefamulin displays activity against gram‐positive and atypical organisms associated with CABP (i.e., Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydophila pneumoniae), with an expanded gram‐positive spectrum including Staphylococcus aureus (i.e., methicillin‐resistant, vancomycin‐intermediate, and heterogeneous strains) and vancomycin‐resistant Enterococcus faecium. Lefamulin was also shown to retain activity against multidrug‐resistant Neisseria gonorrhoeae and Mycoplasma genitalium. Lefamulin exhibits time‐dependent killing, and the pharmacodynamic target best associated with antibacterial activity is ƒAUC0–24/MIC (minimum inhibitory concentration [MIC]). Preclinical and phase II trials indicate that lefamulin concentrates in lung tissue are well tolerated at an IV dose of 150 mg twice/day over 1 hour or a PO dose of 600 mg twice/day, and preliminary phase III data suggest similar efficacy when compared with moxifloxacin with or without linezolid in CABP. Documented resistance and cross‐resistance with other gram‐positive antibacterials remains low. Additional published in vitro, in vivo, and preclinical trial data suggest further exploration of lefamulin in various infectious disease states (e.g., acute bacterial skin and skin structure infections, and sexually transmitted infections). This review discusses the pertinent bacterial spectrum of activity, preclinical and ongoing clinical data, and potential roles in therapy for lefamulin.
A comparative study of three commonly used fixation techniques for isolated medial malleolus fracture.

OBJECTIVES This study aims to compare the three most commonly used fixation techniques: tension-band wire fixation, partially threaded cannulated screws, and fully threaded cannulated headless compression screws. PATIENTS AND METHODS Ninety patients with medial malleolus fractures were included in the study. Patients were divided into three groups. Group A included patients who underwent tension-band wire fixation (n=26), Group B partially threaded cannulated compression screws (n=32), and Group C fully threaded cannulated headless compression screws (n=32). The type of medial malleolus fracture, healing rates, implant-related complications, rate of infection, hardware removal, weight-bearing restrictions, mean interval time from the injury to the surgery, and Body Mass Indexes (BMIs) were investigated. The patients' radiographs (standard anteroposterior, lateral, and mortise) were reviewed. The American Orthopedic Foot and Ankle Society (AOFAS) scoring system was used for clinical evaluation. RESULTS No significant difference was observed between the three groups in terms of age, gender, BMI, follow-up period, and fracture type. Union rate for group C was significantly shorter than groups A and B. There was no implant failure or irritation in group C and this was statistically significant comparing to group A and B (p=0.037). However, there was no significant difference between group A and B (p=0.41). There were no significant differences in the three groups according to AOFAS. Patients with low BMI in groups A and B had a high rate of implant-related complications. There was a significant correlation between low BMI and implant-related complication (p<0.001). CONCLUSION Union rate in the group who were operated with fully threaded cannulated headless compression screws was significantly shorter than the other groups. This study has shown that tension band wiring and partially threaded cannulated compression screws can cause irritation of soft tissues and pain over the hardware implantation site. Patients with low BMI are vulnerable for implant-related complications.
Maternal Protective Parenting Accounts for the Relationship Between Pain Behaviors and Functional Disability in Adolescents

Introduction: A variety of factors influence parent responses to pain behaviors they observe in their adolescents with chronic pain. Certain parental responses to pain, such as attention or overprotection, can adversely impact adolescent adaptive functioning and correspond to poor clinical outcomes. Objectives: It was hypothesized that the relationship between adolescent pain behaviors and functional disability was mediated by maladaptive parenting (protective, monitoring, solicitousness) responses. Materials and Methods: Participants were 303 adolescents and their mothers presenting to a pain clinic. Adolescents completed measures of functional disability and pain intensity; mothers completed measures assessing adolescent pain behaviors, their own catastrophizing about their adolescent’s pain, and responses to pain. A path model tested the direct and indirect associations between pain behaviors and disability via 3 parenting responses, controlling for average pain intensity and parent pain catastrophizing. Results: Greater pain behavior was associated with increased protective responses (&agr; path, P<0.001); greater protective behavior was associated with increased disability (&bgr; path, P=0.002). Including parenting responses in the model, the path between pain behaviors and disability remained significant (c′ path, P<0.001). The indirect path between pain behaviors and disability via parenting responses was significant for protective responses (P<0.02), controlling for pain intensity and parent pain catastrophizing. The indirect effect of protective responses explained 18% of the variance between pain behaviors and disability. Discussion: Observing adolescent pain behaviors may prompt parents to engage in increased protective behavior that negatively impacts adolescents’ functioning, even after controlling for the effects of parental pain catastrophizing.
Long‐term outcomes and predictors of morbi‐mortality according to age in stemi patients with multivessel disease: Impact of an incomplete revascularization

Optimal management strategy for patients with ST‐segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) still remains unclear, especially in the elderly population. The aim of this study was to assess long‐term outcomes and predictors of morbi‐mortality according to age in patients with a STEMI and MVD.
Adenocarcinoma histology is a poor prognostic factor in locally advanced cervical cancer

Abstract Objective: This retrospective study aimed to compare prognostic factors and survival between adenocarcinoma (AC) and squamous cell carcinoma (SCC) in locally advanced cervical cancer treated at a single center. Methods: All medical records of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB or IIIA,B, treated between 2004 and 2012, were reviewed. We treated patients with chemoradiotherapy (CRT) followed by brachytherapy (BT). Multivariate logistic regression and Cox proportional hazard models were used to analyze clinicopathological characteristics, patterns of care and outcomes. Results: We included in the analysis 161 patients (52 AC; 109 SCC). Patients with AC were younger (age 50 vs. 55 years), more likely to die from the disease (HR: 1.60; 95% CI: 1.26–2.58; p = .001) and to have disease recurrence (HR: 1.69; 95% C.I: 1.21–2.12; p = .004) than those with SCC. The other significant prognostic factors for overall survival (OS) and recurrence-free survival (RFS) in AC were FIGO stage (p = .001; p = .002), WHO status (0 vs. 1–3; p = .003; p = .04), and hemoglobin level (<12 g/dl>; p = .04; p = .02). The 5 year overall survival for stage II of AC and SCC was 63% and 82% (p = .03), and for IIIA,B it was 33.6% and 73% (p = .0005). The 5 year RFS for AC and SCC stage FIGO IIIA,B was 24% and 57% (p = .001). Conclusions: Adenocarcinoma histology negatively impacts OS and RFS for advanced cervical cancer. Histology-specific therapy may be an opportunity for survival improvement in these women.
Cytokines Produced by Dendritic Cells Administered Intratumorally Correlate with Clinical Outcome in Patients with Diverse Cancers

Purpose: Dendritic cells (DC) initiate adaptive immune responses through the uptake and presentation of antigenic material. In preclinical studies, intratumorally injected activated DCs (aDCs; DCVax-Direct) were superior to immature DCs in rejecting tumors from mice. Experimental Design: This single-arm, open-label phase I clinical trial evaluated the safety and efficacy of aDCs, administered intratumorally, in patients with solid tumors. Three dose levels (2 million, 6 million, and 15 million aDCs per injection) were tested using a standard 3 + 3 dose-escalation trial design. Feasibility, immunogenicity, changes to the tumor microenvironment after direct injection, and survival were evaluated. We also investigated cytokine production of aDCs prior to injection. Results: In total, 39 of the 40 enrolled patients were evaluable. The injections of aDCs were well tolerated with no dose-limiting toxicities. Increased lymphocyte infiltration was observed in 54% of assessed patients. Stable disease (SD; best response) at week 8 was associated with increased overall survival. Increased secretion of interleukin (IL)-8 and IL12p40 by aDCs was significantly associated with survival (P = 0.023 and 0.024, respectively). Increased TNFα levels correlated positively with SD at week 8 (P < 0.01). Conclusions: Intratumoral aDC injections were feasible and safe. Increased production of specific cytokines was correlated with SD and prolonged survival, demonstrating a link between the functional profile of aDCs prior to injection and patient outcomes. Clin Cancer Res; 24(16); 3845–56. ©2018 AACR.
Cis-regulatory determinants of MyoD function

Abstract Muscle-specific transcription factor MyoD orchestrates the myogenic gene expression program by binding to short DNA motifs called E-boxes within myogenic cis-regulatory elements (CREs). Genome-wide analyses of MyoD cistrome by chromatin immnunoprecipitation sequencing shows that MyoD-bound CREs contain multiple E-boxes of various sequences. However, how E-box numbers, sequences and their spatial arrangement within CREs collectively regulate the binding affinity and transcriptional activity of MyoD remain largely unknown. Here, by an integrative analysis of MyoD cistrome combined with genome-wide analysis of key regulatory histones and gene expression data we show that the affinity landscape of MyoD is driven by multiple E-boxes, and that the overall binding affinity—and associated nucleosome positioning and epigenetic features of the CREs—crucially depend on the variant sequences and positioning of the E-boxes within the CREs. By comparative genomic analysis of single nucleotide polymorphism (SNPs) across publicly available data from 17 strains of laboratory mice, we show that variant sequences within the MyoD-bound motifs, but not their genome-wide counterparts, are under selection. At last, we show that the quantitative regulatory effect of MyoD binding on the nearby genes can, in part, be predicted by the motif composition of the CREs to which it binds. Taken together, our data suggest that motif numbers, sequences and their spatial arrangement within the myogenic CREs are important determinants of the cis-regulatory code of myogenic CREs.