Miracle-dz/UniFAR-FTUs huggingface dataset:
Sustained lung inflation at birth via short binasal prong in very low birth weight preterm infants: A retrospective study

It is believed, that sustained lung inflation (SLI) at birth in preterm infants reduces the need for mechanical ventilation (MV) and improves respiratory outcomes. The aim of this study was to compare need for MV in preterm infants at high risk for respiratory distress syndrome (RDS) after prophylactic SLI via short binasal prongs at birth combined with early nasal continuous positive airway pressure (nCPAP) versus nCPAP alone.
Diagnostic Biomarkers of Epilepsy.

BACKGROUND Diagnostic biomarkers of epilepsy are objectively measurable variables associated with the development of epilepsy or the propensity to generate seizures. Identification of biomarkers could be helpful for differential diagnosis and for tailored therapeutic approaches. OBJECTIVE This review focuses on diagnostic biomarkers of epilepsy, including genetic, serological, neuroimaging and electrophysiological variables. METHODS References were mainly identified through PubMed search until December 2017 and backtracking of references in pertinent studies. RESULTS Several promising diagnostic biomarkers of epilepsy exist, with causative value or predicting liability to develop seizures after acquired brain injuries. Short non-coding RNAs are deregulated in serum and cerebral tissue of epilepsy subjects: these molecules are promising diagnostic biomarkers, being easy to assess and reproducible. Advanced imaging techniques may allow identification of subtle epileptogenic lesions, often with prognostic value. Novel electrophysiological biomarkers of epilepsy include perturbed cortical connectivity and excitability induced by transcranial magnetic stimulation, as well as high-frequency oscillations detected by intracranial and scalp electroencephalographic recordings. Finally, serological biomarkers may support the differential diagnosis between epileptic seizures and non-epileptic events. CONCLUSION Ongoing research on diagnostic biomarkers of epilepsy is promising and future preclinical and clinical studies are warranted.
Regulation of cyclin E1 expression in human pluripotent stem cells and derived neural progeny

ABSTRACT Human pluripotent stem cells (hPSCs), including embryonic and induced pluripotent stem cells (hESCs and hiPSCs) show unique cell cycle characteristics, such as a short doubling time due to an abbreviated G1 phase. Whether or not the core cell cycle machinery directly regulates the stemness and/or the differentiation potential of hPSCs remains to be determined. To date, several scenarios describing the atypical cell cycle of hPSCs have been suggested, and therefore there is still controversy over how cyclins, master regulators of the cell cycle, are expressed and regulated. Furthermore, the cell cycle profile and the expression pattern of major cyclins in hESCs-derived neuroprogenitors (NP) have not been studied yet. Therefore, herein we characterized the expression pattern of major cyclins in hPSCs and NP. We determined that all studied cyclins mRNA expression levels fluctuate along cell cycle. Particularly, after a thorough analysis of synchronized cell populations, we observed that cyclin E1 mRNA levels increased sharply in G1/S concomitantly with cyclin E1 protein accumulation in hPSCs and NP. Additionally, we demonstrated that cyclin E1 mRNA expression levels involves the activation of MEK/ERK pathway and the transcription factors c-Myc and E2Fs in hPSCs. Lastly, our results reveal that proteasome mediates the marked down-regulation (degradation) of cyclin E1 protein observed in G2/M by a mechanism that requires a functional CDK2 but not GSK3β activity. Abbreviations: hPSCs: human pluripotent stem cells; hESCs: human embryonic stem cells; hiPSCs: human induced pluripotent stem cells; NP: neuroprogenitors; HF: human foreskin fibroblasts; MEFs: mouse embryonic fibroblasts; iMEFs: irradiated mouse embryonic fibroblasts; CDKs: cyclindependent kinases; CKIs: CDK inhibitors; CNS: central nervous system; Oct-4: Octamer-4; EB: embryoid body; AFP: Alpha-fetoprotein; cTnT: Cardiac Troponin T; MAP-2: microtubule-associated protein; TUJ-1: neuron-specific class III β-tubulin; bFGF: basic fibroblastic growth factor; PI3K: Phosphoinositide 3-kinase; KSR: knock out serum replacement; CM: iMEF conditioned medium; E8: Essential E8 medium
An Optimized System for Effective Derivation of Three‐Dimensional Retinal Tissue via Wnt Signaling Regulation

Effective derivation of three‐dimensional (3D) retinal tissue from human‐induced pluripotent stem cells (hiPSCs) could provide models for drug screening and facilitate patient‐specific retinal cell replacement therapy. However, some hiPSC lines cannot undergo 3D self‐organization and show inadequate differentiation efficiency to meet clinical demand. In this study, we developed an optimized system for derivation of 3D retinal tissue. We found that the Wnt signaling pathway antagonist Dickkopf‐related protein 1 (DKK‐1) rescued the inability of differentiated retinal progenitors to self‐organize. By evaluating DKK‐1 expression and supplying DKK‐1 if necessary, retinal organoids were differentiated from six hiPSC lines, which were reprogramed from three common initiating cell types. Retinal tissues derived from the optimized system were well organized and capable of surviving for further maturation. Thus, using this system, we generated retinal tissues from various hiPSC lines with high efficiency. This novel system has many potential applications in regenerative therapy and precision medicine. Stem Cells 2018;36:1709–1722
Lattice Microarchitecture for Bone Tissue Engineering from Calcium Phosphate Compared to Titanium

Additive manufacturing of bone tissue engineering scaffolds will become a key element for personalized bone tissue engineering in the near future. Several additive manufacturing processes are based on extrusion where the deposition of the filament will result in a three-dimensional lattice structure. Recently, we studied diverse lattice structures for bone tissue engineering realized by laser sintering of titanium. In this work, we used lithography-based ceramic manufacturing of lattice structures to produce scaffolds from tricalcium phosphates (TCP) and compared them in vivo to congruent titanium scaffolds manufactured with the identical computer-aided design data to look for material-based differences in bony healing. The results show that, during a 4-week period in a noncritical-size defect in a rabbit calvarium, both scaffolds with the identical microarchitecture performed equally well in terms of bony regeneration and bony bridging of the defect. A significant increase in both parameters could only be achieved when the TCP-based scaffolds were doped with bone morphogenetic protein-2. In a critical-size defect in the calvarial bone of rabbits, however, the titanium scaffold performed significantly better than the TCP-based scaffold, most likely due to its higher mechanical stability. We conclude that titanium and TCP-based scaffolds of the same microarchitecture perform equally well in terms of bone regeneration, provided the microarchitecture meets the mechanical demand at the site of implantation.
Repetitive head injury in adolescent mice: A role for vascular inflammation

Repetitive mild traumatic brain injury during adolescence can induce neurological dysfunction through undefined mechanisms. Interleukin-1 (IL-1) contributes to experimental adult diffuse and contusion TBI models, and IL-1 antagonists have entered clinical trials for severe TBI in adults; however, no such data exist for adolescent TBI. We developed an adolescent mouse repetitive closed head injury (rCHI) model to test the role of IL-1 family members in post-injury neurological outcome. Compared to one CHI, three daily injuries (3HD) produced acute and chronic learning deficits and emergence of hyperactivity, without detectable gliosis, neurodegeneration, brain atrophy, and white matter loss at one year. Mature IL-1β and IL-18 were induced in brain endothelium in 3HD but not 1HD, three hit weekly, or sham animals. IL-1β processing was induced cell-autonomously in three-dimensional human endothelial cell cultures subjected to in vitro concussive trauma. Mice deficient in IL-1 receptor-1 or caspase-1 had improved post-injury Morris water maze performance. Repetitive mild CHI in adolescent mice may induce behavioral deficits in the absence of significant histopathology. The endothelium is a potential source of IL-1β and IL-18 in rCHI, and IL-1 family members may be therapeutic targets to reduce or prevent neurological dysfunction after repetitive mild TBI in adolescents.
Treatment outcomes and HIV drug resistance of patients switching to second-line regimens after long-term first-line antiretroviral therapy

Abstract To investigate the responses to switching to second-line regimens among patients who had received a long-term first-line antiretroviral therapy. Patients switching to second-line regimens from June 2008 to June 2015 were enrolled from an observational cohort. In addition, patients continuing first-line therapy and had a viral load <1000 copies/mL were included as controls in July 2012. All these patients were followed-up for 36 months or until June 2016. The virological, immunological outcomes, and drug resistance were evaluated. Virological failure was defined as viral load ≥1000 copies/mL after 6 months of treatment since the start of the study. There were 304 patients switching to second-line regimens and 46 patients remaining on first-line therapy enrolled while having received first-line therapy for a median of 7.6 years. Patients with plasma viral load (VL) ≥1000 copies/mL before switching to second-line regimens had a sharp decline in the proportion of virological failure with 26.7%, 20.4%, and 17.0% at 12, 24, and 36 months after regimen switch, respectively (trend test, P < .001). Among these patients, individuals with drug resistance (DR) had a better virological responses as compared with those without DR after regimen switching. While patients with VL <1000 copies/mL at inclusion remained a high rate of viral suppression after switching to second-line regimens. So did patients continuing first-line therapy. Among patients with VL ≥1000 copies/mL before switching to second-line regimens, the rates of drug resistance were decreased from 79.4% at inclusion to 7.5% at 36 months of regimen switch, with the proportion of NRTI- and NNRTI-related drug resistance from 67.2% and 79.4% to 5.4% and 7.5%, respectively. No PI-related resistance was found. Having self-reported missing doses within a month at follow-ups were independently associated with virological failure at 36 months of switching. HIV-infected patients had viral load ≥1000 copies/mL at regimen switch after a long duration of first-line therapy had good virological responses to second-line regimens, especially those harbored drug resistant variants at regimen switch. However, patients with suppressive first-line therapy did not appear to benefit virologically from switching to second-line regimens.
Defining Multimorbidity in Older Surgical Patients

Background: There are numerous definitions of multimorbidity (MM). None systematically examines specific comorbidity combinations accounting for multiple testing when exploring large datasets. Objectives: Develop and validate a list of all single, double, and triple comorbidity combinations, with each individual qualifying comorbidity set (QCS) more than doubling the odds of mortality versus its reference population. Patients with at least 1 QCS were defined as having MM. Research Design: Cohort-based study with a matching validation study. Subjects: All fee-for-service Medicare patients between age 65 and 85 without dementia or metastatic solid tumors undergoing general surgery in 2009–2010, and an additional 2011–2013 dataset. Measures: 30-day all-location mortality. Results: There were 576 QCSs (2 singles, 63 doubles, and 511 triples), each set more than doubling the odds of dying. In 2011, 36% of eligible patients had MM. As a group, multimorbid patients (mortality rate=7.0%) had a mortality Mantel-Haenszel odds ratio=1.90 (1.77–2.04) versus a reference that included both multimorbid and nonmultimorbid patients (mortality rate=3.3%), and Mantel-Haenszel odds ratio=3.72 (3.51–3.94) versus only nonmultimorbid patients (mortality rate=1.6%). When matching 3151 pairs of multimorbid patients from low-volume hospitals to similar patients in high-volume hospitals, the mortality rates were 6.7% versus 5.2%, respectively (P=0.006). Conclusions: A list of QCSs identified a third of older patients undergoing general surgery that had greatly elevated mortality. These sets can be used to identify vulnerable patients and the specific combinations of comorbidities that make them susceptible to poor outcomes.
A machine learning method to monitor China’s AIDS epidemics with data from Baidu trends

Background AIDS is a worrying public health issue in China and lacks timely and effective surveillance. With the diffusion and adoption of the Internet, the ‘big data’ aggregated from Internet search engines, which contain users’ information on the concern or reality of their health status, provide a new opportunity for AIDS surveillance. This paper uses search engine data to monitor and forecast AIDS in China. Methods A machine learning method, artificial neural networks (ANNs), is used to forecast AIDS incidences and deaths. Search trend data related to AIDS from the largest Chinese search engine, Baidu.com, are collected and selected as the input variables of ANNs, and officially reported actual AIDS incidences and deaths are used as the output variable. Three criteria, the mean absolute percentage error, the root mean squared percentage error, and the index of agreement, are used to test the forecasting performance of the ANN method. Results Based on the monthly time series data from January 2011 to June 2017, this article finds that, under the three criteria, the ANN method can lead to satisfactory forecasting of AIDS incidences and deaths, regardless of the change in the number of search queries. Conclusions Despite the inability to self-detect HIV/AIDS through online searching, Internet-based data should be adopted as a timely, cost-effective complement to a traditional AIDS surveillance system.
Opposing effects of intracellular versus extracellular adenine nucleotides on autophagy: implications for β-cell function

ABSTRACT AMPK–mTORC1 signaling senses nutrient availability, thereby regulating autophagy. Surprisingly, we found that, in β-cells, the AMPK activator 5-amino-4-imidazolecarboxamide ribofuranoside (AICAR) inhibited, rather than stimulated, autophagy. AICAR is an intermediate in the generation of inosine monophosphate, with subsequent conversion to other purine nucleotides. Adenosine regulated autophagy in a concentration-dependent manner: at high concentrations, it mimicked the AICAR effect on autophagy, whereas at low concentrations it stimulated autophagy through its cognate A1 receptor. Adenosine regulation of autophagy was independent of AMPK or mTORC1 activity. Adenosine kinase (ADK) is the principal enzyme for metabolic adenosine clearance. ADK knockdown and pharmacological inhibition of the enzyme markedly stimulated autophagy in an adenosine A1 receptor-dependent manner. High-concentration adenosine increased insulin secretion in a manner sensitive to treatment with the autophagy inducer Tat-beclin1, and inhibition of autophagy augmented secretion. In conclusion, high concentrations of AICAR or adenosine inhibit autophagy, whereas physiological concentrations of adenosine or inhibition of adenosine clearance by ADK stimulate autophagy via the adenosine receptor. Adenosine might thus be an autocrine regulator of autophagy, independent of AMPK–mTORC1 signaling. Adenosine regulates insulin secretion, in part, through modulation of autophagy. Summary: Adenosine and its metabolism by adenosine kinase regulate autophagy independent of nutrient availability and the canonical AMPK–mTORC1 pathway. In β-cells, adenosine regulates insulin secretion, in part, through modulation of autophagy.
Magnetic nanocellulose hybrid nanoparticles and ionic liquid for extraction of neonicotinoid insecticides from milk samples prior to determination by liquid chromatography-mass spectrometry

ABSTRACT A simple and rapid microextraction procedure is reported on the use of ionic liquid in combination with magnetic nanocellulose hybrid nanoparticles. The procedure is ultrasound-assisted and applicable to selective preconcentration of neonicotinoid insecticides from milk samples, prior to being analysed by liquid chromatography-mass spectrometry. The extraction procedure uses small volume of organic solvents (<1 mL), and there is no need for centrifugation. In the experimental approach the ionic liquid was quickly disrupted by an ultrasonic probe and dispersed in milk samples in a cloudy form. At this stage, neonicotinoid insecticides were extracted into the fine droplets of ionic liquid. Then small amounts of magnetic nanocellulose hybrid nanoparticles were dispersed into the sample solutions to adsorb the ionic liquid containing the analytes and phase separation was completed. The ionic liquid allowed the microextraction of the analytes and a small volume of acetonitrile was used for elution. Magnetic nanocellulose favoured the adsorption of the ionic liquid with the analytes and improved the final recovery with respect to the use of simple magnetic nanoparticles as a sorbent material. Under the optimum conditions, decision capabilities were achieved in the 0.02–0.06 mg kg−1 range, with recoveries between 91.0% and 109.5%. GRAPHICAL ABSTRACT
Animal influence on water, sanitation and hygiene measures for zoonosis control at the household level: A systematic literature review

Introduction Neglected zoonotic diseases (NZDs) have a significant impact on the livelihoods of the world’s poorest populations, which often lack access to basic services. Water, sanitation and hygiene (WASH) programmes are included among the key strategies for achieving the World Health Organization’s 2020 Roadmap for Implementation for control of Neglected Tropical Diseases (NTDs). There exists a lack of knowledge regarding the effect of animals on the effectiveness of WASH measures. Objectives This review looked to identify how animal presence in the household influences the effectiveness of water, hygiene and sanitation measures for zoonotic disease control in low and middle income countries; to identify gaps of knowledge regarding this topic based on the amount and type of studies looking at this particular interaction. Methods Studies from three databases (Medline, Web of Science and Global Health) were screened through various stages. Selected articles were required to show burden of one or more zoonotic diseases, an animal component and a WASH component. Selected articles were analysed. A narrative synthesis was chosen for the review. Results Only two studies out of 7588 met the inclusion criteria. The studies exemplified how direct or indirect contact between animals and humans within the household can influence the effectiveness of WASH interventions. The analysis also shows the challenges faced by the scientific community to isolate and depict this particular interaction. Conclusion The dearth of studies examining animal-WASH interactions is explained by the difficulties associated with studying environmental interventions and the lack of collaboration between the WASH and Veterinary Public Health research communities. Further tailored research under a holistic One Health approach will be required in order to meet the goals set in the NTDs Roadmap and the 2030 Agenda for Sustainable Development.
Huber’s Non-Linearity for GNSS Interference Mitigation †

Satellite-based navigation is prevalent in both commercial applications and critical infrastructures, providing precise position and time referencing. As a consequence, interference to such systems can have repercussions on a plethora of fields. Additionally, Privacy Preserving Devices (PPD)—jamming devices—are relatively inexpensive and easy to obtain, potentially denying the service in a wide geographical area. Current jamming mitigation technology is based on interference cancellation approaches, requiring the detection and estimation of the interference waveform. Recently, the Robust Interference Mitigation (RIM) framework was proposed, which leverages results in robust statistics by treating the jamming signal as an outlier. It has the advantage of rejecting jamming signals without detecting or estimating its waveform. In this paper, we extend the framework to situations where the jammer is sparse in some transformed domain other than the time domain. Additionally, we analyse the use of Huber’s non-linearity within RIM and derive its loss of efficiency. We compare its performance to state-of-the-art techniques and to other RIM solutions, with both synthetic and real signals, showing remarkable results.
Celiac Disease and Liver Disorders: From Putative Pathogenesis to Clinical Implications

Immunologically mediated liver diseases belong to the common extraintestinal manifestations of celiac disease. We have reviewed the current literature that addresses the association between celiac disease and liver disorders. We searched relevant articles on MEDLINE/PubMed up to 15 June 2018. The objective of the article is to provide a comprehensive and up-to-date review on the latest hypotheses explaining the pathogenetic relationship between celiac disease and liver injury. Besides the involvement of gut–liver axis, tissue transglutaminase antibodies, and impairment of intestinal barrier, we integrate the latest achievements made in elucidation of the role of gut microbiota in celiac disease and liver disorders, that has not yet been sufficiently discussed in the literature in this context. The further objective is to provide a complete clinical overview on the types of liver diseases frequently found in celiac disease. In conclusion, the review highlights the clinical implication, recommend a rational approach for managing elevated transaminases in celiac patients, and underscore the importance of screening for celiac disease in patients with associated liver disease.
Influence of initial mathematical competencies on the effectiveness of a classroom‐based intervention

BACKGROUND Students commonly struggle with mathematics and mathematical problem-solving. Therefore, it is necessary to design and implement interventions aimed at improving these essential components of learning. Furthermore, the outcomes of these interventions can vary significantly and appear to be a function of a student's initial competencies in mathematics. AIM This study attempts to analyse the influence of initial levels of mathematics competency with respect to the benefits of a specific intervention known as the Integrated Dynamic Representation (IDR). SAMPLE Participants were 288 students (aged 6-8 years) who were divided according to their levels of mathematics competency (low-medium-high). METHODS Students were assigned to the two primary intervention groups, experimental group (EG; students who received the IDR intervention) and control group (CG; students who followed the traditional instructional methods). All participants completed the Test of Early Mathematics Abilities (TEMA-3) both before and after the intervention. RESULTS AND CONCLUSIONS Although all the three competency levels of the EG improved, the progression was different for each level. Results showed that students with low competency level improved substantially more than the students with medium and/or high baseline competency level.