Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal Study Investigating the Relationship between Disease Activity and Psychological Status of Patients with Behçet’s Disease

ABSTRACT Purpose To compare longitudinal changes in disease activity with quality of life and psychological status in patients with Behçet’s disease (BD). Methods Patients attending a National Centre of Excellence for BD over a two-year period had disease activity including clinician and patient perception of disease documented and completed a number of validated quality of life and psychological questionnaires. Some representative case-studies were examined in detail. Results 102 patients were included. Disease activity weakly correlated with quality of life and psychological health. Clinician and patient perceptions strongly correlated with each other. Case-study analyses showed diverse, and sometimes incongruous, responses between, and in, individual patients. Conclusion Changes in disease activity account for only a small proportion of changes in psychological status with intra-individual variation playing a large role. There is a complex relationship between psychological status and disease activity that cannot be explained by changes in disease activity alone.
Hormones in Breast Milk and Effect on Infants’ Growth: A Systematic Review

Breast milk is characterized by a dynamic and complex composition which includes hormones and other bioactive components that could influence infant growth, development, and optimize health. Among the several beneficial effects associated with prolonged breastfeeding, a 13% decrease in the risk of overweight and obesity has been reported. Recent research has focused on breast milk hormones contributing to the appetite and energy balance regulation and adiposity. Accordingly, we conducted a literature systematic review with the aim to provide an update on the effect of leptin, ghrelin, Insulin Growth Factor 1, adiponectin, and insulin on infants’ and children’s growth and body composition. The revised literature reveals contrasting findings concerning the potential role of all these hormones on modeling growth and fat mass apposition and health outcomes later in life. Further studies are needed to gain further insight into the specific role of these bioactive components in metabolic pathways related to body composition. This could help gain a further insight on infants’ growth, both in physiological and pathological settings.
Cell-free prototyping of AND-logic gates based on heterogeneous RNA activators

RNA-based devices controlling gene expression bear great promise for synthetic biology, as they offer many advantages like short response times and light metabolic burden compared to protein-circuits. However, little work has been done regarding their integration to multi-level regulated circuits. In this work, we combined a variety of small transcriptional activator RNAs (STARs) and toehold switches to build highly effective AND-gates. To characterise the components and their dynamic range, we used an Escherichia coli (E. coli) cell-free transcription-translation (TX-TL) system dispensed via nanoliter droplets. We analysed a prototype gate in vitro as well as in silico, employing parameterised ordinary differential equations (ODEs), where parameters were inferred via parallel tempering, a Markov chain Monte Carlo (MCMC) method. Based on this analysis, we created nine additional AND-gates and tested them in vitro. The functionality of the gates was found to be highly dependent on the concentration of the activating RNA for either the STAR or the toehold switch. All gates were successfully implemented in vivo, offering a dynamic range comparable to the level of protein circuits. This study shows the potential of a rapid prototyping approach for RNA circuit design, using cell-free systems in combination with a model prediction. Abbreviations TX-TL (transcription-translation), ODEs (ordinary differential equations), STARs (small transcriptional activator RNAs), MCMC (Markov chain Monte Carlo).
Telomerase RNAs in land plants

Abstract To elucidate the molecular nature of evolutionary changes of telomeres in the plant order Asparagales, we aimed to characterize telomerase RNA subunits (TRs) in these plants. The unusually long telomere repeat unit in Allium plants (12 nt) allowed us to identify TRs in transcriptomic data of representative species of the Allium genus. Orthologous TRs were then identified in Asparagales plants harbouring telomere DNA composed of TTAGGG (human type) or TTTAGGG (Arabidopsis-type) repeats. Further, we identified TRs across the land plant phylogeny, including common model plants, crop plants, and plants with unusual telomeres. Several lines of functional testing demonstrate the templating telomerase function of the identified TRs and disprove a functionality of the only previously reported plant telomerase RNA in Arabidopsis thaliana. Importantly, our results change the existing paradigm in plant telomere biology which has been based on the existence of a relatively conserved telomerase reverse transcriptase subunit (TERT) associating with highly divergent TRs even between closely related plant taxa. The finding of a monophyletic origin of genuine TRs across land plants opens the possibility to identify TRs directly in transcriptomic or genomic data and/or predict telomere sequences synthesized according to the respective TR template region.
Validity of Physical Exam Maneuvers in the Diagnosis of Sacroiliac Joint Pathology.

BACKGROUND A combination of physical examination maneuvers is currently considered necessary to help predict who will respond to injections in the sacroiliac joint. However, the literature on this topic currently consists of conflicting studies, with one showing the value of a combination of exam maneuvers and the other showing no real value. OBJECTIVE To determine the diagnostic validity of sacroiliac joint (SIJ) physical exam maneuvers using anesthetic intra-articular injection as a reference standard. DESIGN A single institution prospective study. PARTICIPANTS Patients with the clinical diagnosis of SIJ pain and referred for SIJ injection were enrolled. MAIN OUTCOME MEASURE Numeric rating scale (NRS) to assess pain intensity. RESULTS Participants underwent fluoroscopically guided SIJ intra-articular injection with 1 cc of 2% lidocaine and 1 cc of triamcinolone 40 mg. Patients' pain was assessed via 0-10 NRS pre-injection and immediately postinjection to determine positive anesthetic response to the injection. Six physical exam maneuvers (thigh thrust, Geanslen's test, FABER test, distraction test, compression test, and sacral thrust) were performed pre-injection and 15 minutes postinjection. The results of these SIJ physical exam maneuvers were evaluated singly and in combinations for diagnostic power in relation to a positive anesthetic response (>80% relief) to the injection. No association was found between a single SIJ physical exam maneuver or combination of maneuvers and anesthetic response to the injection. CONCLUSIONS In this cohort, patient physical exam maneuvers to identify intra-articular SIJ pain did not demonstrate diagnostic value when compared with the reference standard of an intra-articular anesthetic block.
Birth and coming of age of islet autoantibodies

This review takes the reader through 45 years of islet autoantibody research, from the discovery of islet‐cell antibodies in 1974 to today’s population‐based screening for presymptomatic early‐stage type 1 diabetes. The review emphasizes the current practical value of, and factors to be considered in, the measurement of islet autoantibodies.
Mechanisms underlying sharpening of visual response dynamics with familiarity

Experience-dependent modifications of synaptic connections are thought to change patterns of network activities and stimulus tuning with learning. However, only a few studies explored how synaptic plasticity shapes the response dynamics of cortical circuits. Here, we investigated the mechanism underlying sharpening of both stimulus selectivity and response dynamics with familiarity observed in monkey inferotemporal cortex. Broadening the distribution of activities and stronger oscillations in the response dynamics after learning provide evidence for synaptic plasticity in recurrent connections modifying the strength of positive feedback. Its interplay with slow negative feedback via firing rate adaptation is critical in sharpening response dynamics. Analysis of changes in temporal patterns also enables us to disentangle recurrent and feedforward synaptic plasticity and provides a measure for the strengths of recurrent synaptic plasticity. Overall, this work highlights the importance of analyzing changes in dynamics as well as network patterns to further reveal the mechanisms of visual learning.
Diagnostic Accuracy of Community-Based Diabetic Retinopathy Screening With an Offline Artificial Intelligence System on a Smartphone.

Importance Offline automated analysis of retinal images on a smartphone may be a cost-effective and scalable method of screening for diabetic retinopathy; however, to our knowledge, assessment of such an artificial intelligence (AI) system is lacking. Objective To evaluate the performance of Medios AI (Remidio), a proprietary, offline, smartphone-based, automated system of analysis of retinal images, to detect referable diabetic retinopathy (RDR) in images taken by a minimally trained health care worker with Remidio Non-Mydriatic Fundus on Phone, a smartphone-based, nonmydriatic retinal camera. Referable diabetic retinopathy is defined as any retinopathy more severe than mild diabetic retinopathy, with or without diabetic macular edema. Design, Setting, and Participants This prospective, cross-sectional, population-based study took place from August 2018 to September 2018. Patients with diabetes mellitus who visited various dispensaries administered by the Municipal Corporation of Greater Mumbai in Mumbai, India, on a particular day were included. Interventions Three fields of the fundus (the posterior pole, nasal, and temporal fields) were photographed. The images were analyzed by an ophthalmologist and the AI system. Main Outcomes and Measures To evaluate the sensitivity and specificity of the offline automated analysis system in detecting referable diabetic retinopathy on images taken on the smartphone-based, nonmydriatic retinal imaging system by a health worker. Results Of 255 patients seen in the dispensaries, 231 patients (90.6%) consented to diabetic retinopathy screening. The major reasons for not participating were unwillingness to wait for screening and the blurring of vision that would occur after dilation. Images from 18 patients were deemed ungradable by the ophthalmologist and hence were excluded. In the remaining participants (110 female patients [51.6%] and 103 male patients [48.4%]; mean [SD] age, 53.1 [10.3] years), the sensitivity and specificity of the offline AI system in diagnosing referable diabetic retinopathy were 100.0% (95% CI, 78.2%-100.0%) and 88.4% (95% CI, 83.2%-92.5%), respectively, and in diagnosing any diabetic retinopathy were 85.2% (95% CI, 66.3%-95.8%) and 92.0% (95% CI, 97.1%-95.4%), respectively, compared with ophthalmologist grading using the same images. Conclusions and Relevance These pilot study results show promise in the use of an offline AI system in community screening for referable diabetic retinopathy with a smartphone-based fundus camera. The use of AI would enable screening for referable diabetic retinopathy in remote areas where services of an ophthalmologist are unavailable. This study was done on patients with diabetes who were visiting a dispensary that provides curative services to the population at the primary level. A study with a larger sample size may be needed to extend the results to general population screening, however.
A Modeling Approach for Investigating Opto-Mechanical Relationships in the Human Eye Lens

Objective: The human visual system alters its focus by a shape change of the eye lens. The extent to which the lens can adjust ocular refractive power is dependent to a significant extent on its material properties. Yet, this fundamental link between the optics and mechanics of the lens has been relatively under-investigated. This study aims to investigate this opto-mechanical link within the eye lens to gain insight into the processes of shape alteration and their respective decline with age. Methods: Finite Element models based on biological lenses were developed for five ages: 16, 35, 40, 57, and 62 years by correlating in vivo measurements of the longitudinal modulus using Brillouin scattering with in vitro X-ray interferometric measurements of refractive index and taking into account various directions of zonular force. Results: A model with radial cortical Young's moduli provides the same amount of refractive power with less change in thickness than a model with uniform cortical Young's modulus with a uniform stress distribution and no discontinuities along the cortico-nuclear boundary. The direction of zonular angles can significantly influence curvature change regardless of the modulus distribution. Conclusions: The present paper proposes a modelling approach for the human lens, coupling optical and mechanical properties, which shows the effect of parameter choice on model response. Significance: This advanced modelling approach, considering the important interplay between optical and mechanical properties, has potential for use in design of accommodating implant lenses and for investigating non-biological causes of pathological processes in the lens (e.g., cataract).
An umbrella review of systematic reviews and meta-analyses

Introduction: Several pharmacological treatments are beneficial for patients with irritable bowel syndrome (IBS), and there are numbers of systematic reviews evaluating the effectiveness of these treatments. However, the overall quality of the evidence has not been quantitatively assessed. The aim of this study is to evaluate the possible biases in the published systematic reviews and determine the treatments with reliable evidence. Methods and analysis: We will perform an umbrella review to identify eligible systematic reviews. A comprehensive literature search will be conducted in MEDLINE, EMBASE, and the Cochrane library for systematic reviews. We will describe the general information such as participants, interventions, outcome measurements, and conclusion. Additionally, the heterogeneity and inconsistency between trials will be assessed by the I statistical test and CochraneQ test. We will assess risk of bias, and summarize the strength evidence. PROSPERO registration number: CRD42018109597 Abbreviations: 5-HT3 = 5-hydroxytryptamine type-3, AMSTAR = A MeaSurement Tool to Assess Systematic Reviews, CSBMs = complete spontaneous bowel movements, FDA = the food and drug administration, IBS = irritable bowel syndrome, IBS-C = irritable bowel syndrome with constipation, IBS-D= irritable bowel syndromewith diarrhea, IBS-M=mixed irritable bowel syndrome, MeSH = medical subject headings, PRISMA-P = the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols, RCTs = randomized controlled trials, , SSRIs = selective serotonin reuptake inhibitors, TCAs = tricyclic antidepressants, VAS = visual analog scale.
The association of problematic smartphone use with family well-being mediated by family communication in Chinese adults: A population-based study

Background and aims Few studies have investigated the effects of problematic smartphone use (PSU) in the family context. We studied the association of PSU as a predictor with family well-being and the potential mediating role of family communication in Hong Kong Chinese adults. Methods We analyzed data of 5,063 randomly selected adults [mean age (SD) = 48.1 (18.2) years; 45.0% men] from a dual landline and mobile telephone survey in 2017. PSU was assessed by the Smartphone Addiction Scale-Short Version with higher scores indicating higher levels. Family well-being was assessed by three questions on perceived family health, harmony, and happiness (3Hs) with higher scores indicating greater well-being. Perceived sufficiency and quality of family communication were rated. Multivariable regression analyses examined (a) associations of PSU with family 3Hs and well-being and (b) mediating role of family communication, adjusting for sociodemographic variables. Results PSU was negatively associated with perceived family health (adjusted β = −0.008, 95% CI = −0.016, −0.0004), harmony (adjusted β = −0.009, 95% CI = −0.017, −0.002), happiness (adjusted β = −0.015, 95% CI = −0.022, −0.007), and well-being (adjusted β = −0.011, 95% CI = −0.018, −0.004). Perceived family communication sufficiency (adjusted β = −0.007, 95% CI = −0.010, −0.005) and quality (adjusted β = −0.009, 95% CI = −0.014, −0.005) mediated the association of PSU with family well-being, with 75% and 94% of total effects having mediated, respectively. Discussion and conclusions PSU was negatively associated with family well-being, which was partially mediated by family communication. Such findings provide insights for health programs to prevent PSU and improve family well-being.
1,25-Dihydroxyvitamin D3 Prevents Epithelial-Mesenchymal Transition of HMrSV5 Human Peritoneal Mesothelial Cells by Inhibiting Histone Deacetylase 3 (HDAC3) and Increasing Vitamin D Receptor (VDR) Expression Through the Wnt/β-Catenin Signaling Pathway

Background Peritoneal dialysis is the most common treatment for end-stage renal disease. However, peritoneal fibrosis resulting from long-term peritoneal dialysis restricts peritoneal ultrafiltration. Previous studies have shown a role for 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) in preventing fibrosis, but the potential mechanisms remain unknown. This study aimed to investigate the role of 1,25(OH)2D3 in epithelial-mesenchymal transition (EMT) and the downstream signaling pathway in HMrSV5 human peritoneal mesothelial cells in vitro. Material/Methods An in vitro cell model of peritoneal fibrosis was established using the HMrSV5 human peritoneal mesothelial cell line. High glucose and lipopolysaccharide (LPS) culture conditions, with or without 1,25(OH)2D3, were used. Wnt agonist 1, a Wnt signaling pathway activator, was applied. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to measure the vitamin D receptor (VDR) and histone deacetylase 3 (HDAC3) gene and protein expression levels, β-catenin, and EMT-associated biomarkers. Results High glucose plus LPS culture medium inhibited cell proliferation, induced cell apoptosis and promoted EMT in HMrSV5 cells, which was reversed by 1,25(OH)2D3 by down-regulation of HDAC3 and upregulation of VDR. HDAC3 inhibited VDR gene expression. The expression of EMT-associated biomarkers was increased by Wnt agonist 1 and inhibited by 1,25(OH)2D3. Conclusions In HMrSV5 human peritoneal mesothelial cells, 1,25(OH)2D3 reversed EMT by inhibiting the expression of HDAC3 and upregulating VDR gene expression via the Wnt/β-catenin signaling pathway.
Lipopolysaccharide and lipoteichoic acid enhance serum amyloid A3 mRNA expression in murine alveolar epithelial cells

Serum amyloid A (SAA) is an acute-phase protein indicative of inflammation. In murine colonic epithelial cells, lipopolysaccharide (LPS), a gram-negative bacterial antigen, strongly enhanced mRNA expression of SAA3, but not SAA1 or SAA2, suggesting that SAA3 might respond to bacterial infection in other epithelia. We examined SAA1/2 and SAA3 mRNA expression in murine alveolar epithelial cells exposed to LPS or the gram-positive bacterial antigen, lipoteichoic acid (LTA), using real-time PCR. LPS enhanced SAA3 mRNA expression at lower concentrations than did LTA, whereas SAA1/2 mRNA expression was not enhanced by either LPS or LTA. These results suggest that SAA3 expression is enhanced in lung epithelium upon bacterial infection as part of innate immunity, with higher sensitivity to LPS than to LTA.
Getting to Know Your Neighbor: Protein Structure Prediction Comes of Age with Contextual Machine Learning

The folding of a protein structure is a process governed by both local and nonlocal interactions. While incorporating local dependencies into a machine learning algorithm for protein structure prediction is simple and has been exploited for some time, the modeling of long-range dependences which result from structurally-neighboring residues has only recently begun to be addressed. Structural properties designed to localize the prediction space from direct tertiary structure prediction, such as secondary structure, contact maps, and intrinsic disorder, among others, have begun to greatly benefit from machine learning models capable of modeling a widened, potentially global protein context. This has led to a direct enhancement of the quality of predicted tertiary structures through both the optimization of structural constraints and improved reliability of alignments to structural templates. These improvements have stemmed from the application of recurrent and convolutional neural network architectures effective not only at innate sequential context propagation but also deep feature extraction due to novel skip connections and normalization techniques allowing for greatly enhanced error back-propagation. The recent results from independent blind testing in Critical Assessment of protein Structure Prediction 13 have signaled the beginning of a new generation of protein structure prediction through the utilization of these contextual techniques. The ripples from advancements in the determination of one-dimensional and two-dimensional structural properties have us moving ever closer to the solution of the protein structure prediction problem.
In vivo imaging with a water immersion objective affects brain temperature, blood flow and oxygenation

Previously, we reported the first oxygen partial pressure (Po2) measurements in the brain of awake mice, by performing two-photon phosphorescence lifetime microscopy at micrometer resolution (Lyons et al., 2016). However, this study disregarded that imaging through a cranial window lowers brain temperature, an effect capable of affecting cerebral blood flow, the properties of the oxygen sensors and thus Po2 measurements. Here, we show that in awake mice chronically implanted with a glass window over a craniotomy or a thinned-skull surface, the postsurgical decrease of brain temperature recovers within a few days. However, upon imaging with a water immersion objective at room temperature, brain temperature decreases by ~2–3°C, causing drops in resting capillary blood flow, capillary Po2, hemoglobin saturation, and tissue Po2. These adverse effects are corrected by heating the immersion objective or avoided by imaging through a dry air objective, thereby revealing the physiological values of brain oxygenation.