Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonpharmacological Interventions for Sleep Promotion on Preterm Infants in Neonatal Intensive Care Unit: A Systematic Review

BACKGROUND Nonpharmacological interventions are often used to promote sleep among preterm infants in the neonatal intensive care unit (NICU). However, there is a lack of synthesis in the evidence of their effectiveness. AIM To synthesize the evidence on the effectiveness of nonpharmacological interventions on NICU preterm infants' sleep during hospital stay. METHODS Seven databases were searched, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Wan-fang database, China National Knowledge Infrastructure, China Biological Medicine Database, and VIP Journal Integration Platform from their inceptions to August 2017. Randomized controlled trials examining the effects of nonpharmacological interventions on preterm infants' sleep were included. RESULTS This review included 36 studies. Nonpharmacological interventions included the Newborn Individualized Developmental Care and Assessment Program (NIDCAP), music, non-nutritive sucking, touch, cycled light, cobedding, rocking, oral sucrose, remolding mattresses, and family nurturing. The meta-analysis results showed that 1. the NIDCAP had no significant effect on total sleep time efficiency (TST%; p = .34); 2. mattress interventions had significant effects on TST% (p < .001); and active sleep efficiency (AS%; p = .006) but no significant effect on quiet sleep efficiency (QS%; p = .75); 3. cycled light increased TST (p = .02); and 4. cobedding had no significant effects on QS% and AS% (p = .63 and p = .88, respectively). LINKING EVIDENCE TO ACTION Remolding mattresses and cycled light had significant effects on sleep promotion in preterm infants, but the quality of the evidence was very low. Further high-quality studies are needed to strengthen this evidence.
Combined inhibition of MEK and PI3K pathways overcomes acquired resistance to EGFR‐TKIs in non‐small cell lung cancer

Compensatory activation of the signal transduction pathways is one of the major obstacles for the targeted therapy of non‐small cell lung cancer (NSCLC). Herein, we present the therapeutic strategy of combined targeted therapy against the MEK and phosphoinositide‐3 kinase (PI3K) pathways for acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC. We investigated the efficacy of combined trametinib plus taselisib therapy using experimentally established EGFR‐TKI‐resistant NSCLC cell lines. The results showed that the feedback loop between MEK/ERK and PI3K/AKT pathways had developed in several resistant cell lines, which caused the resistance to single‐agent treatment with either inhibitor alone. Meanwhile, the combined therapy successfully regulated the compensatory activation of the key intracellular signals and synergistically inhibited the cell growth of those cells in vitro and in vivo. The resistance mechanisms for which the dual kinase inhibitor therapy proved effective included (MET) mesenchymal‐epithelial transition factor amplification, induction of epithelial‐to‐mesenchymal transition (EMT) and EGFR T790M mutation. In further analysis, the combination therapy induced the phosphorylation of p38 MAPK signaling, leading to the activation of apoptosis cascade. Additionally, long‐term treatment with the combination therapy induced the conversion from EMT to mesenchymal‐to‐epithelial transition in the resistant cell line harboring EMT features, restoring the sensitivity to EGFR‐TKI. In conclusion, our results indicate that the combined therapy using MEK and PI3K inhibitors is a potent therapeutic strategy for NSCLC with the acquired resistance to EGFR‐TKIs.
Surface Quality Enhancement of Fused Deposition Modeling (FDM) Printed Samples Based on the Selection of Critical Printing Parameters

The present paper shows an experimental study on additive manufacturing for obtaining samples of polylactic acid (PLA). The process used for manufacturing these samples was fused deposition modeling (FDM). Little attention to the surface quality obtained in additive manufacturing processes has been paid by the research community. So, this paper aims at filling this gap. The goal of the study is the recognition of critical factors in FDM processes for reducing surface roughness. Two different types of experiments were carried out to analyze five printing parameters. The results were analyzed by means of Analysis of Variance, graphical methods, and non-parametric tests using Spearman’s ρ and Kendall’s τ correlation coefficients. The results showed how layer height and wall thickness are the most important factors for controlling surface roughness, while printing path, printing speed, and temperature showed no clear influence on surface roughness.
The unusual flagellar-targeting mechanism and functions of the trypanosome ortholog of the ciliary GTPase Arl13b

ABSTRACT The small GTPase Arl13b is one of the most conserved and ancient ciliary proteins. In human and animals, Arl13b is primarily associated with the ciliary membrane, where it acts as a guanine-nucleotide-exchange factor (GEF) for Arl3 and is implicated in a variety of ciliary and cellular functions. We have identified and characterized Trypanosoma brucei (Tb)Arl13, the sole Arl13b homolog in this evolutionarily divergent, protozoan parasite. TbArl13 has conserved flagellar functions and exhibits catalytic activity towards two different TbArl3 homologs. However, TbArl13 is distinctly associated with the axoneme through a dimerization/docking (D/D) domain. Replacing the D/D domain with a sequence encoding a flagellar membrane protein created a viable alternative to the wild-type TbArl13 in our RNA interference (RNAi)-based rescue assay. Therefore, flagellar enrichment is crucial for TbArl13, but mechanisms to achieve this could be flexible. Our findings thus extend the understanding of the roles of Arl13b and Arl13b–Arl3 pathway in a divergent flagellate of medical importance. This article has an associated First Person interview with the first author of the paper. Highlighted Article: All roads lead to cilia – how the essential flagellar enrichment of Arl13 is achieved in trypanosome cells using a fundamentally different strategy compared with that of animal cells.
Anesthesia challenges for emergency surgery in a pediatric patient with congenital laryngomalacia

1. Wong GK, Arab AA, Chew SC, Naser B, Crawford MW. Major complications related to epidural analgesia in children: A 15‐year audit of 3,152 epidurals. Can J Anaesth 2013;60:355‐63. 2. Forero M, Adhikary SD, Lopez H, Tsui C, Chin KJ. The erector spinae plane block: A novel analgesic technique in thoracic neuropathic pain. Reg Anesth Pain Med 2016;41:621‐7. 3. Muñoz F, Cubillos J, Bonilla AJ, Chin KJ. Erector spinae plane block for postoperative analgesia in pediatric oncological thoracic surgery. Can J Anaesth 2017;64:880‐2. 4. Ueshima H, Otake H. Clinical experiences of ultrasound‐guided erector spinae plane block for thoracic vertebra surgery. J Clin Anesth 2017;38:137.
Myocardial Contraction during the Diastolic Isovolumetric Period: Analysis of Longitudinal Strain by Means of Speckle Tracking Echocardiography

Background: According to the ventricular myocardial band model, the diastolic isovolumetric period is a contraction phenomenon. Our objective was to employ speckle-tracking echocardiography (STE) to analyze myocardial deformation of the left ventricle (LV) and to confirm if it supports the myocardial band model. Methods: This was a prospective observational study in which 90 healthy volunteers were recruited. We evaluated different types of postsystolic shortening (PSS) from an LV longitudinal strain study. Duration of latest deformation (LD) was calculated as the time from the start of the QRS complex of the ECG to the latest longitudinal deformation peak in the 18 segments of the LV. Results: The mean age of our subjects was 50.3 ± 11.1 years. PSS was observed in 48.4% of the 1620 LV segments studied (19.8%, 13.5%, and 15.1% in the basal, medial, and apical regions, respectively). PSS was more frequent in the basal, medial septal, and apical anteroseptal segments (>50%). LD peaked in the interventricular septum and in the basal segments of the LV. Conclusions: The pattern of PSS and LD revealed by STE suggests there is contraction in the postsystolic phase of the cardiac cycle. The anatomical location of the segments in which this contraction is most frequently observed corresponds to the main path of the ascending component of the myocardial band. This contraction can be attributed to the protodiastolic untwisting of the LV.
Extrusion 3D Printing of Paracetamol Tablets from a Single Formulation with Tunable Release Profiles Through Control of Tablet Geometry

An extrusion-based 3D printer was used to fabricate paracetamol tablets with different geometries (mesh, ring and solid) from a single paste-based formulation formed from standard pharmaceutical ingredients. The tablets demonstrate that tunable drug release profiles can be achieved from this single formulation even with high drug loading (> 80% w/w). The tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed well-defined release profiles (from immediate to sustained release) controlled by their different geometries. The dissolution results showed dependency of drug release on the surface area/volume (SA/V) ratio and the SA of the different tablets. The tablets with larger SA/V ratios and SA had faster drug release. The 3D printed tablets were also evaluated for physical and mechanical properties including tablet dimension, drug content, weight variation and breaking force and were within acceptable range as defined by the international standards stated in the US Pharmacopoeia. X-ray powder diffraction, differential scanning calorimetry and attenuated total reflectance Fourier transform infrared spectroscopy were used to identify the physical form of the active and to assess possible drug-excipient interactions. These data again showed that the tablets meet USP requirement. These results clearly demonstrate the potential of 3D printing to create unique pharmaceutical manufacturing, and potentially clinical, opportunities. The ability to use a single unmodified formulation to achieve defined release profiles could allow, for example, relatively straightforward personalization of medicines for individuals with different metabolism rates for certain drugs and hence could offer significant development and clinical opportunities.
Dynamic Monitoring and Vibration Analysis of Ancient Bridges by Ground-Based Microwave Interferometry and the ESMD Method

In this paper, we propose to conduct a dynamic monitoring and vibration analysis of ancient bridges by means of ground-based microwave interferometry and the extreme-point symmetric mode decomposition (ESMD) method. Ground-based microwave interferometry, a novel non-contact technology with a high accuracy, is used to acquire dynamic time series displacements with environmental excitation factors and a transient load with a car, respectively. The ESMD method, a new alternative to the Hilbert-Huang transform (HHT), is adopted to conduct the instantaneous vibration analysis of Zhaozhou Bridge. Firstly, a series of intrinsic mode functions (IMFs) are obtained together with an optimal adaptive global mean (AGM) curve by using a mode symmetric about the maxima and minima points. Secondly, the instantaneous frequency of each IMF is obtained by the use of a direct interpolation algorithm, which can reconcile the conflict between the period and the frequency for the traditional time-frequency analysis methods. As a representative case, Zhaozhou Bridge, a well-known Chinese ancient bridge constructed more than 1400 years ago, is studied in detail. Four kinds of dynamic time series displacements—two of them acquired by considering only environmental excitation factors for the mid-span and 1/4-span points and the others obtained with the transient load of a car for the mid-span and 1/4-span points—are selected to pursue a comparison of the decomposed IMFs and the instantaneous frequencies to perform the instantaneous vibration analysis of Zhaozhou Bridge. By comparing the results obtained with HHT for the decomposed IMFs and the instantaneous frequencies, the results show that the proposed method has a powerful ability to evaluate the instantaneous dynamic response of ancient bridges.
The association between birth order and childhood leukemia may be modified by paternal age and birth weight. Pooled results from the International Childhood Cancer Cohort Consortium (I4C)

The “delayed infection hypothesis” states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population‐based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 106 person‐years of follow‐up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77–0.99) and 0.85: (0.73–0.99), respectively. Being later‐born was associated with similarly reduced hazards of CL and ALL compared to being first‐born; HRs = 0.78: 95% CI: 0.58–1.05 and 0.73: 0.52–1.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (p = 0.024) and paternal age (p = 0.067), respectively, in associations between being later‐born and CL, with the lowest risk observed for children born at <3 kg with fathers aged 35+ (HR = 0.18, 95% CI: 0.06–0.50). Our study strengthens the theory that increasing birth order confers protection against CL and ALL risks, but suggests that this association may be modified among subsets of children with different characteristics, notably advanced paternal age and lower birth weight. It is unclear whether these findings can be explained solely by infectious exposures.
Comparison of two rapid diagnostic tests during a large dengue virus serotype 3 outbreak in the Solomon Islands in 2013

Dengue virus (DENV) infection causes various clinical presentations, including asymptomatic infection, dengue with or without warning signs and severe dengue. An early and accurate diagnosis of DENV infection during the first few days of illness supports clinical management and significantly reduces dengue-associated mortality and morbidity. However, it is very difficult to confirm DENV infection in endemic regions without qualified dengue diagnostic laboratories. In this study, we evaluated the performance of two commercially available rapid diagnostic tests (RDTs) using serum samples collected in the Solomon Islands during the 2013 DENV-3 outbreak. The sensitivity and specificity of the tests were calculated by comparing the results of DENV nonstructural protein 1 (NS1), IgM and IgG RDTs with those obtained by qRT-PCR. We also compared the results of the DENV IgM/IgG RDT with those obtained using an IgM/IgG capture enzyme-linked immune-sorbent assay (ELISA). The sensitivities of the SD and CTK NS1 RDTs were similar (90.9% and 92.6%), and the specificity of the SD NS1 RDT was significantly higher than that of the CTK NS1 RDT (100% versus 78.8%). The inclusion of IgM and IgG in the RDT did not significantly increase the sensitivity for DENV diagnosis. Compared with the SD IgM RDT, IgM capture ELISA had the same specificity but higher sensitivity. User-friendly RDTs remain the first choice and the most convenient tool in dengue endemic regions, where laboratory facilities and the corresponding infrastructure are lacking. Our study provided important and practical information for comparing the performance and validity of the different RDTs for rapid dengue detection.
A survey on orthopedic injuries during a marathon sled dog race

Purpose This prospective observational study aimed to describe and quantify orthopedic injuries (OI) during a marathon sled dog race that led to discontinuation of racing (dropped dogs [DDs]) and to suggest potential associations with risk factors during the event. Study design Prospective observational study. Animals A total of 989 Nordic breed endurance sled dogs that participated in the 2011 Iditarod Sled Dog Race. Data were collected via an extensive questionnaire, medical records, and speed calculations based on Global Positioning System equipment on each dog sled. OI risk factors and DD incidence were statistically analyzed on dogs and teams completing at least half the race distance, including Student’s t-test, Pearson’s chi-squared test, Poisson regression, and various frailty analysis models as indicated. Significance was set at P<0.10 for inclusion in the models with trends established at P≤0.10 and significance declared at P<0.05. Results Questionnaire response was 40.3%. DD incidence was 38.3%, most often due to OI (50.6%). OI occurred most frequently in the thoracic limb (43.3%) compared with pelvic limb injuries (7.3%). Increased speed was associated with fewer shoulder injuries (Ratio=0.65, P=0.03). Carpal injuries were positively related with increased conditioning distance (defined as training miles; Hazard ratio =1.61, P=0.02). The risk to become a DD decreased with every year of increased age of the dogs (Hazard ratio =0.92, P=0.03). Conclusion OI, specifically of the shoulder and carpus, are common in marathon sled dogs. Injury risk may be speed-related and decreases with increasing age of the dog. Further study of environmental, dietary, and trail conditions in sled dog racing orthopedic research is needed.
The Effectiveness of Continuous Glucose Monitoring in Patients with Type 2 Diabetes: A Systematic Review of Literature and Meta-analysis.

BACKGROUND Continuous glucose monitoring (CGM) provides glucose trend information that can be used to guide treatment and motivate patients with diabetes. Currently, the evidence on effectiveness of CGM in patients with type 2 diabetes is debatable. We aim to provide a systematic review and meta-analysis to synthesize current evidence of effectiveness of CGM in adults with type 2 diabetes. MATERIALS AND METHODS Cochrane, Embase, PubMed, and Web of Science were searched to include all studies that reported effectiveness of CGM in terms of HbA1c in adults aged 18 and older, with type 2 diabetes, on any treatment for diabetes. Heterogeneity (I2) was used to determine the variability between studies. All data were analyzed using Review Manager 5.3 software. RESULTS Seven randomized controlled trials and three cohort studies, involving 1384 patients for real-time CGM (RT-CGM) and professional CGM (P-CGM) and 4902 patients for flash glucose monitoring (FGM), were included. RT-CGM and P-CGM were associated with a modest but statistically significant reduction in HbA1c of 0.20% (95% confidence interval [CI] -0.31 to -0.09) compared with control. Patients who received FGM had a nonsignificant reduction of 0.02% (95% CI -0.07 to 0.04) compared with control. The meta-analysis indicated a low heterogeneity between studies. CONCLUSION Our analysis of current evidence suggests that RT-CGM and P-CGM are effective in improving HbA1c in adults with type 2 diabetes. Due to insufficient evidence, it is premature to form conclusions on the effectiveness of FGM. Future multicenter trials accessing the effectiveness of CGM as well as safety and cost-effectiveness may be necessary.
Everolimus in infants with tuberous sclerosis complex–related West syndrome: First results from a single‐center prospective observational study

Tuberous sclerosis complex (TSC) is the most common cause of West syndrome (WS). Currently available treatment options are ineffective in the majority of affected infants and/or associated with potential serious side effects. Based on the assumption that mTOR overactivation results in increased neuroexcitability in TSC, mTOR inhibitors have been studied as antiseizure therapy. As a result, everolimus recently received approval for the adjunctive treatment of patients aged ≥2 years with refractory TSC‐associated focal and secondary generalized seizures. However, efficacy and safety data for infants with TSC‐associated WS are still lacking. Therefore, a prospective open‐label observational study was initiated at our center, to evaluate everolimus add‐on treatment in infants with TSC‐associated WS, previously refractory to standard treatment. For this preliminary report, data from four male infants with TSC2 and a median observation period of 13 (range = 8‐42) months after treatment initiation were analyzed. Two infants showed electroclinical remission until day 14 after everolimus treatment initiation. In one additional infant, hypsarrhythmia resolved. No relapse after initial response was documented. Developmental progress improved in three infants. Tolerability was similar to that described in older children. According to our preliminary results, everolimus appears to have the potential to treat successfully both spasms and hypsarrhythmia in infants with TSC‐associated WS, contributing to better developmental progress.
Anti-CD20 monoclonal antibodies: reviewing a revolution

ABSTRACT Since the inception of rituximab in the 1990s, anti-CD20 monoclonal antibodies have revolutionised the treatment of B cell hematological malignancies and have become a cornerstone of modern gold-standard practice. Additionally, the potent efficacy of these agents in depleting the B cell compartment has been used in the management of a broad array of autoimmune diseases. Multiple iterations of these agents have been investigated and are routinely used in clinical practice. In this review, we will discuss the physiology of CD20 and its attractiveness as a therapeutic target, as well as the pharmacology, pre-clinical and clinical data for the major anti-CD20 monoclonal antibodies: rituximab, obinutuzumab and ofatumumab.
Swine Influenza Virus Induces RIPK1/DRP1-Mediated Interleukin-1 Beta Production

Nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3) inflammasome plays a pivotal role in modulating lung inflammation in response to the influenza A virus infection. We previously showed that the swine influenza virus (SIV) infection induced NLRP3 inflammasome-mediated IL-1β production in primary porcine alveolar macrophages (PAMs), and we were interested in examining the upstream signaling events that are involved in this process. Here, we report that the SIV-infection led to dynamin-related protein 1 (DRP1) phosphorylation at serine 579 and mitochondrial fission in PAMs. IL-1β production was dependent on the reactive oxygen species (ROS) production, and DRP1 phosphorylation resulted in the upregulation of the NLRP3 inflammasome. Furthermore, the requirement of the kinase activity of receptor-interacting protein kinase 1 (RIPK1) for the IL-1β production and RIPK1-DRP1 association suggested that RIPK1 is an upstream kinase for DRP1 phosphorylation. Our results reveal a critical role of the RIPK1/DRP1 signaling axis, whose activation leads to mitochondrial fission and ROS release, in modulating porcine NLRP3 inflammasome-mediated IL-1β production in SIV-infected PAMs.