Miracle-dz/UniFAR-FTUs huggingface dataset:
Entrapped in cage (EiC) scaffolds of 3D-printed polycaprolactone and porous silk fibroin for meniscus tissue engineering

The meniscus has critical functions in the knee joint kinematics and homeostasis. Injuries of the meniscus are frequent, and the lack of a functional meniscus between the femur and tibial plateau can cause articular cartilage degeneration leading to osteoarthritis development and progression. Regeneration of meniscus tissue has outstanding challenges to be addressed. In the current study, novel Entrapped in cage (EiC) scaffolds of 3D-printed polycaprolactone (PCL) and porous silk fibroin were proposed for meniscus tissue engineering. As confirmed by micro-structural analysis the entrapment of silk fibroin was successful, and all scaffolds had excellent interconnectivity (≥99%). The EiC scaffolds had more favorable micro-structure compared with the PCL cage scaffolds by improving the pore size while keeping the interconnectivity almost the same. When compared with the PCL cage, the entrapment of porous silk fibroin into the PCL cage decreased the high compressive modulus in a favorable matter in the wet state thanks to the silk fibroin’s high swelling properties. The in vitro studies with human stem cells or meniscocytes seeded constructs, demonstrated that the EiC scaffolds had superior cell adhesion, metabolic activity, and proliferation compared to the PCL cage scaffolds. Upon subcutaneous implantation of scaffolds in nude mice, all groups were free of adverse incidents, and mildly invaded by inflammatory cells with neovascularization, while the EiC scaffolds showed better tissue infiltration. The results of this work indicated that the EiC scaffolds of PCL and silk fibroin are favorable for meniscus tissue engineering, and the findings are encouraging for further studies using a larger animal model.
Superhydrophobic Methylated Silica Sol for Effective Oil–Water Separation

Superhydrophobic methylated silica with a core–shell structure was successfully fabricated by a sol-gel process. First, a pristine silica gel with an average particle size of ca. 110 nm was prepared, using tetraethylorthosilicate (TEOS) as a precursor, ethanol as a solvent, and NH4OH as a catalyst. Then, the superhydrophobic methylated silica sol was prepared by introducing methyltrimethoxysilane (MTMS), to graft the surface of the pristine silica gel with methyl groups. The structure and morphology of the methylated silica sol were characterized by Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FE-SEM), and transmission electron microscope (TEM). The characterization results showed that methyl groups were successfully grafted onto the surface of the pristine silica, and the diameter of the methylated silica was increased by 5–10 nm. Various superhydrophobic surfaces on glass, polyethylene terephthalate (PET) fabric, cotton, open-cell polyurethane (PU) foam, and polypropylene (PP) filter cloth were successfully constructed by coating the above substrates with the methylated silica sol and reached with a maximum static water contact angle and slide angle of 161° and 3°, respectively. In particular, the superhydrophobic PP filter cloth exhibited promising application in oil–water separation. The separation efficiency of different oil–water mixtures was higher than 96% and could be repeated at least 15 times.
Experimental boundary conditions of reinstatement-induced return of fear in humans: Is reinstatement in humans what we think it is?

Experimental paradigms used to study reinstatement of fear in humans are characterized by procedural heterogeneity. Reinstatement protocols involve unexpected (re)-presentations of the unconditioned stimulus (USs) after fear extinction training. Here, we address the number of reinstatement USs administered as a potential boundary condition that may explain divergent findings in the field. A sample of 171 participants is exposed to a fear acquisition training, immediate extinction training, and reinstatement test experiment. Three groups differing in the number of reinstatement US are employed: one (n = 57) or four (n = 55) in experimental groups and zero (n = 59) in the control group. We adopt Bayesian statistical approaches beyond classical null hypothesis significance testing (NHST) to qualify evidence for or against this potential methodological boundary condition in reinstatement-induced return of fear. Startle potentiation to the reinstatement administration context was increased for the RI-USone compared to the RI-USzero group, supporting the role of context conditioning in reinstatement. This effect was weaker in the RI-USfour group. This, however, did not transfer to responding to conditioned stimuli during the return of fear-test: no evidence for an effect of the number of reinstatement USs (zero, one, four) was observed in behavioral or physiological measures. In sum, our results speak against the number of reinstatement USs as a potential boundary condition in experimentally induced return of fear in humans. This may challenge what we think we know about the reinstatement phenomenon in humans and call for critical reconsideration of paradigms as well as mechanisms that may underlie some reinstatement effects in the literature.
The follicular microenvironment in low (++) and high (I+B+) ovulation rate ewes.

Ewes with single copy mutations in GDF9, BMP15 or BMPR1B have smaller preovulatory follicles containing fewer granulosa cells (GC), whilst developmental competency of the oocyte appears to be maintained. We hypothesised that similarities and/or differences in follicular maturation events between wildtype (++) ewes and mutant ewes with single copy mutations in BMP15 and BMPR1B (I+B+), are key to the attainment of oocyte developmental competency, and for increasing ovulation rate (OR) without compromising oocyte quality. Developmental competency of oocytes from I+B+ animals was confirmed following embryo transfer to recipient ewes. The microenvironment of both growing and presumptive preovulatory (PPOV) follicles from ++ and I+B+ ewes was investigated. When grouped according to gonadotropin-responsiveness, PPOV follicles from I+B+ ewes had smaller mean diameters with fewer GC than equivalent follicles in ++ ewes (OR = 4.4 ± 0.7 and 1.7 ± 0.2, respectively; P<0.001). Functional differences between these genotypes included differential gonadotropin-responsiveness of GC, follicular fluid composition and expression levels of cumulus cell-derived VCAN, PGR, EREG, BMPR2 genes. A unique microenvironment was characterised in I+B+ follicles as they underwent maturation. Our evidence suggests that GC were less metabolically-active, resulting in increased follicular fluid concentrations of amino acids and metabolic substrates, potentially protecting the oocyte from ROS. Normal expression levels of key genes linked to oocyte quality and embryo survival in I+B+ follicles supports the successful lambing percentage of transferred I+B+ oocytes. In conclusion, these I+B+ oocytes develop normally, despite radical changes in follicular size and GC number induced by these combined heterozygous mutations.
Rise of the Rxivs: How Preprint Servers are Changing the Publishing Process

Abstract Scientific publishing is a complex and time-consuming process. Submitting an article to a journal, waiting for review, and revising can take months or even years. Authors can speed up parts of this process by posting early versions their articles online to gather feedback and improve them prior to submission to a journal. These early versions are referred to as “preprints. ” Preprints have been common practice in some disciplines for decades, but are a relatively new phenomenon in biology and medicine. This column will provide a brief history of article preprints and their use in different scientific disciplines. It will also discuss the advantages of and problems with preprints. A list of popular preprint servers is also included.
Effect of salt reduction interventions in lowering blood pressure in Chinese populations: a systematic review and meta-analysis of randomised controlled trials

Rationale and objective Salt reduction remains a global challenge and different salt reduction strategies have been studied in China. This study is to systematically evaluate evidence from randomised controlled trials (RCT) in China and inform the effective salt reduction strategies. Design Systematic review and meta-analysis. Data sources MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Wanfang Data and the China National Knowledge Infrastructure databases through October 2019. Eligibility criteria RCTs conducted in China with at least 4 weeks’ duration of study and blood pressure (BP) reported. Data extraction and synthesis Data were screened, extracted and appraised by two independent reviewers. The quality of study was assessed using a modified Cochrane Collaboration’s risk of bias tool. The primary outcome was the difference in BP change from baseline to the end of study between interventions and control. The effects were pooled using a random effects model and associated factors were explored by a meta-regression. Results We identified 24 studies involving 10 448 participants, including 8 studies on health education (4583 participants), 2 studies on salt restriction diet (162 participants), 1 study on salt restriction spoon (50 participants) and 13 studies on salt substitute (5653 participants). Six studies on salt substitute and three studies on health education were identified with high quality. Pooled results from the six studies showed that salt substitutes significantly reduced systolic BP (−5.7 mm Hg; 95% CI −8.5 to −2.8) and diastolic BP (−2.0 mm Hg; 95% CI −3.5 to −0.4). The School-EduSalt study showed that the school-based health education significantly reduced systolic BP among parents (−2.3 mm Hg; 95% CI −4.5 to −0.04). Conclusions Among four salt reduction strategies studied in China with RCT design, only salt substitute was proved effective in lowering BP by the pooled effect from multiple studies with high quality. More well-designed studies are warranted for other strategies.
Association of objectively measured physical fitness during pregnancy with maternal and neonatal outcomes. The GESTAFIT Project

Aim To analyse i) the association of physical fitness during early second trimester and late pregnancy with maternal and neonatal outcomes; and ii) to investigate whether physical fitness is associated with the type of birth (vaginal or caesarean section). Methods Pregnant women from the GESTAFIT Project (n = 159) participated in this longitudinal study. Maternal physical fitness including upper- and lower-body strength, cardiorespiratory fitness (CRF) and flexibility were measured through objective physical fitness tests at the 16th and 34th gestational weeks. Maternal and neonatal outcomes were collected from obstetric medical records. Umbilical arterial and venous blood gas pH and partial pressure of carbon dioxide (PCO2) and oxygen (PO2), were assessed. Results At the 16th week, greater upper-body muscle strength was associated with greater neonatal birth weight (r = 0.191, p<0.05). Maternal flexibility was associated with a more alkaline arterial pH (r = 0.220, p<0.05), higher arterial PO2 (r = 0.237, p<0.05) and lower arterial PCO2 (r = -0.331, p<0.01) in umbilical cord blood. Maternal CRF at the 16th gestational week was related to higher arterial umbilical cord PO2 (r = 0.267, p<0.05). The women who had caesarean sections had lower CRF (p<0.001) at the 16th gestational week and worse clustered overall physical fitness, both at the 16th (-0.227, p = 0.003, confidence interval (CI): -0.376, -0.078) and 34th gestational week (-0.223; p = 0.018; CI: -0.432, -0.015) compared with the women who had vaginal births. Conclusion Increasing physical fitness during pregnancy may promote better neonatal outcomes and is associated with a decrease in the risk of caesarean section. This trial was registered at ClinicalTrials.gov (NCT02582567) on October 20, 2015.
PBX3 in Cancer

PBX3 is a homeodomain-containing transcription factor of the pre-B cell leukemia (PBX) family, members of which have extensive roles in early development and some adult processes. A number of features distinguish PBX3 from other PBX proteins, including the ability to form specific and stable interactions with DNA in the absence of cofactors. PBX3 has frequently been reported as having a role in the development and maintenance of a malignant phenotype, and high levels of PBX3 tumor expression have been linked to shorter overall survival in cancer. In this review we consider the similarities and differences in the function of PBX3 in different cancer types and draw together the core signaling pathways involved to help provide a better insight into its potential as a therapeutic target.
Measurement Instruments to Assess Functional Mobility in Parkinson's Disease: A Systematic Review

Functional mobility (FM) is a person's ability to move to accomplish activities of daily living; it bridges the concepts of mobility and functional ability. There is frequently a loss of FM in Parkinson's disease (PD). Several instruments have been used to assess this concept in PD; however, there is no consensus on which are the most appropriate.
Molecularly Imprinted Polymers and Surface Imprinted Polymers Based Electrochemical Biosensor for Infectious Diseases

Owing to their merits of simple, fast, sensitive, and low cost, electrochemical biosensors have been widely used for the diagnosis of infectious diseases. As a critical element, the receptor determines the selectivity, stability, and accuracy of the electrochemical biosensors. Molecularly imprinted polymers (MIPs) and surface imprinted polymers (SIPs) have great potential to be robust artificial receptors. Therefore, extensive studies have been reported to develop MIPs/SIPs for the detection of infectious diseases with high selectivity and reliability. In this review, we discuss mechanisms of recognition events between imprinted polymers with different biomarkers, such as signaling molecules, microbial toxins, viruses, and bacterial and fungal cells. Then, various preparation methods of MIPs/SIPs for electrochemical biosensors are summarized. Especially, the methods of electropolymerization and micro-contact imprinting are emphasized. Furthermore, applications of MIPs/SIPs based electrochemical biosensors for infectious disease detection are highlighted. At last, challenges and perspectives are discussed.
Pharmacotherapy of hypertension in patients with pre-dialysis chronic kidney disease

ABSTRACT Introduction Hypertension is the most common co-morbidity in patients with chronic kidney disease (CKD), with prevalence gradually increasing across CKD Stages to the extent that about 90% of end-stage renal disease (ESRD) patients are hypertensives. Several factors contribute to blood pressure (BP) elevation and guide the therapeutic interventions that should be employed in these patients. Areas covered This review summarizes the existing data for the management of hypertension, regarding optimal BP targets and the use of major antihypertensive classes in patients with CKD. Expert opinion Management of hypertension in CKD requires both lowering BP levels and reducing proteinuria to minimize the risk of both CKD progression and cardiovascular disease. In this respect, aggressive control of office BP to levels <130/80 mmHg has long been proposed for patients with proteinuric nephropathies. Following evidence from recent studies that confirmed significant reductions in renal and cardiovascular outcomes with strict BP control, most, but not all, of international guidelines, suggest such BP goals for all hypertensive patients, including those with CKD. Use of renin-angiotensin system (RAS) blockers is the treatment of choice for patients with proteinuric nephropathies, while, in most patients with CKD, combination treatment with two, three, or more antihypertensive agents is often required to control BP.
Open-label placebo treatment of women with premenstrual syndrome: study protocol of a randomised controlled trial

Introduction Recent evidence suggests that for certain clinical conditions, placebos can improve clinical outcomes even without deception. These so-called open-label placebos (OLPs) bear the advantage of a significant lower risk of adverse events and comply with ethical principles. Although premenstrual syndrome (PMS) seems to be considerably susceptible to placebo effects, no study has examined open-OLP responses on PMS. Methods and analysis To test the efficacy of OLPs in women suffering from PMS, a clinical randomised controlled trial including two OLP study groups (with and without treatment rationale) was designed to investigate on the effect on PMS. PMS symptoms are monitored on a daily basis via a symptom diary, adverse events are monitored intermittently. The study started in spring 2018 and patients will be included until a maximum of 150 participants are randomised. Besides the primary outcome PMS symptom intensity and interference, an array of further variables is assessed. Multilevel modelling will be used for data analyses. Ethics and dissemination Ethics approval was obtained from the Ethics Committee Northwest and Central Switzerland. Results of the main analysis and of secondary analyses will be submitted for publication in peer-reviewed journals. Trial registration numbers (1) ClinicalTrials.gov (NCT03547661); (2) Swiss national registration (SNCTP000002809).
Personalized Models of Psychopathology.

The personalized approach to psychopathology conceptualizes mental disorder as a complex system of contextualized dynamic processes that is nontrivially specific to each individual, and it seeks to develop formal idiographic statistical models to represent these individual processes. Although the personalized approach draws on long-standing influences in clinical psychology, there has been an explosion of research in recent years following the development of intensive longitudinal data capture and statistical techniques that facilitate modeling of the dynamic processes of each individual's pathology. Advances are also making idiographic analyses scalable and generalizable. We review emerging research using the personalized approach in descriptive psychopathology, precision assessment, and treatment selection and tailoring, and we identify future challenges and areas in need of additional research. The personalized approach to psychopathology holds promise to resolve thorny diagnostic issues, generate novel insights, and improve the timing and efficacy of interventions. Expected final online publication date for the Annual Review of Clinical Psychology, Volume 16 is May 7, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Triglycerides and residual risk.

PURPOSE OF REVIEW To review the recent evidence from observational/genetic/interventional studies addressing triglycerides and residual cardiovascular risk (CVRisk). RECENT FINDINGS Large population-based and secondary prevention studies consistently show an association of higher triglycerides with increased CVRisk. This is compounded by genetic studies demonstrating an independent relationship between triglyceride raising or lowering genetic variants affecting triglyceride-rich lipoproteins (TRL) metabolism and CVRisk. Mendelian randomization analysis suggests the benefit of genetic lowering of triglycerides and LDL-cholesterol is similar per unit change in apolipoprotein-B. Among cholesterol-lowering trials, more intensive statin therapy produced greater CVRisk reductions in patients with higher TRL-cholesterol or triglycerides; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition led to similar triglycerides reduction but greater non-HDL-C or apolipoprotein-B reductions than fibrates or fish oils. Regarding n-3 fatty acids, A Study of Cardiovascular Events in Diabetes (ASCEND) and Vitamin D and Omega-3 Trial (VITAL) primary prevention trials with eicosapentaenoic acid (EPA) and docosahexaenoic acid failed to demonstrate cardiovascular benefits, Conversely, Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) using high-dose icosapent-ethyl (purified EPA) in primary (diabetes) and secondary prevention with hypertriglyceridemia showed significant cardiovascular events reductions (greater than expected by the observed triglycerides or apolipoprotein-B reductions, suggesting potential benefits through non-lipid pathways). SUMMARY Evidence suggests higher triglycerides are a marker of CVRisk and may help identify patients who benefit from intensification of therapy. Moreover, genetic studies support a causal link between TRL/triglycerides and cardiovascular disease. Treatment with high-dose EPA may be of benefit in high-risk patients with hypertriglyceridemia to reduce CVRisk.
Development of a system based on artificial intelligence to identify visual problems in children: study protocol of the TrackAI project

Introduction Around 70% to 80% of the 19 million visually disabled children in the world are due to a preventable or curable disease, if detected early enough. Vision screening in childhood is an evidence-based and cost-effective way to detect visual disorders. However, current screening programmes face several limitations: training required to perform them efficiently, lack of accurate screening tools and poor collaboration from young children. Some of these limitations can be overcome by new digital tools. Implementing a system based on artificial intelligence systems avoid the challenge of interpreting visual outcomes. The objective of the TrackAI Project is to develop a system to identify children with visual disorders. The system will have two main components: a novel visual test implemented in a digital device, DIVE (Device for an Integral Visual Examination); and artificial intelligence algorithms that will run on a smartphone to analyse automatically the visual data gathered by DIVE. Methods and analysis This is a multicentre study, with at least five centres located in five geographically diverse study sites participating in the recruitment, covering Europe, USA and Asia. The study will include children aged between 6 months and 14 years, both with normal or abnormal visual development. The project will be divided in two consecutive phases: design and training of an artificial intelligence (AI) algorithm to identify visual problems, and system development and validation. The study protocol will consist of a comprehensive ophthalmological examination, performed by an experienced paediatric ophthalmologist, and an exam of the visual function using a DIVE. For the first part of the study, diagnostic labels will be given to each DIVE exam to train the neural network. For the validation, diagnosis provided by ophthalmologists will be compared with AI system outcomes. Ethics and dissemination The study will be conducted in accordance with the principles of Good Clinical Practice. This protocol was approved by the Clinical Research Ethics Committee of Aragón, CEICA, on January 2019 (Code PI18/346). Results will be published in peer-reviewed journals and disseminated in scientific meetings. Trial registration number ISRCTN17316993.