Miracle-dz/UniFAR-FTUs huggingface dataset:
Systemic lupus erythematosus and pregnancy: the challenge of improving antenatal care and outcomes

Objectives The objective of this article is to describe maternal and perinatal outcomes in women with systemic lupus erythematosus (SLE) followed in a high-risk prenatal outpatient clinic at a referral center. Methods This observational study included pregnant women with SLE who underwent prenatal follow-up and childbirth at the Women’s Hospital, University of Campinas, from January 2012 to January 2018. All women were followed according to the institution’s protocol for pregnant women with SLE. They were subdivided into two groups according to the presence of disease activity during the preconception and gestation periods, and evaluated according to the Systemic Lupus Erythematosus Disease Activity Index and Systemic Lupus Erythematosus Pregnancy Disease Activity Index scales. Data were retrieved from patients’ medical records. Chi-square, Fisher exact and Mann-Whitney tests and multivariable analyses were performed. Statistical significance level was 5% (p < .05). Results A total of 125 cases were initially included; those who were lost to follow-up or gave birth at another hospital were further excluded, with 102 pregnancies (of 95 women) remaining. The mean age of the women was 27.7 years (SD 5.44), and 48% were in their first gestation. The average duration of disease was 6.79 years (SD 5.38), with 92.1% receiving SLE-specific therapy. SLE flare occurred in 8.9% during the preconception period and 23.5% during gestation. Preterm premature rupture of membranes (16.6%), preeclampsia or eclampsia (15.6%) and preterm labor (12.7%) were the most frequent complications. The mean gestational age at birth was 34.4 weeks (SD 5.9); the preterm birth rate was 46.8%, the low birth weight rate was 35.1%, and intensive neonatal care admission was 40.4%. Four fetal deaths and one maternal death occurred, all of them in the group with SLE flares. Multivariable logistic regression analysis showed that preconception lupus activity had a six-fold increased rate of gestational loss (odds ratio (OR): 6.14 (95% confidence interval (CI) 1.26–29.99)), and lupus activity during pregnancy had a five-fold increased rate of prematurity at less than 34 weeks (OR: 5.02 (95% CI: 1.90–13.30)). Conclusions Despite the low percentages of women with pregestational and pregnancy-active disease, we found high incidences of maternal and perinatal complications. Preconception SLE activity increased gestational loss, and SLE activity during pregnancy increased prematurity. Effective immunosuppressive therapy was able to decrease clinical and laboratory activity of SLE; however, unfavorable perinatal outcomes still occurred, even when lupus activity was under control. Pregnancy in women with SLE is always a challenge.
Gender, smoking and blood pressure and the initial presentation of a wide range of cardiovascular diseases : prospective cohort study in 1.5 million patients using linked electronic health records

Background: Myocardial infarction (MI) and stroke are the predominant endpoints of large-scale epidemiological research on cardiovascular disease (CVD) in healthy populations. This thesis capitalised on opportunities presented by linked electronic health records (EHR) to investigate the association of risk factors with the initial presentation of a wide range of pathologically diverse CVDs, with a focus on gender differences. Objective: To determine whether gender, smoking and blood pressure have homogeneous associations with the initial presentation of a range of CVDs. Design: Cohort studies using data from the CALIBER research platform linking four data sources (primary care, disease registry, hospitalisation and mortality records) for 1,758,584 patients free from symptomatic CVD registered with 225 UK general practices between 2001 and 2010. Main outcome measures: Initial presentation of CVD with stable angina, unstable angina, MI, heart failure, ventricular arrhythmias, coronary death, stroke, abdominal aortic aneurysm (AAA) and peripheral arterial disease (PAD). Results: 69% of initial presentations of CVD (N=95,267) were neither MI nor stroke. Men had higher rates of all presentations, with age-adjusted gender rate ratios from 1.23 (95% confidence interval 1.19-1.27)) for stroke to 4.27 (3.92-4.65) for AAA. The association of current smoking (compared to non-smoking) varied from an age-adjusted hazard ratio (HR) of 1.01 (0.90-1.13) for arrhythmia to 4.71 (4.15-5.35) for AAA. Gender differences were found only for MI (women: 2.59 (2.37-2.83); men: 2.20 (2.05-2.37)) and AAA (women: 7.00 (5.64-8.70); men: 3.88 (3.33-4.53)). The association of systolic blood pressure was similar across all CVD presentations, excepting AAA, ranging from age-adjusted HR of 1.19 (1.16-1.22) per standard deviation (SD) for heart failure to 1.28 (1.24-1.31) for PAD, with minimal gender differences. Conclusions: Gender, smoking and blood pressure had heterogeneous associations across a wide range of initial CVD presentations. The implications of these findings for public health, clinical practice and research are discussed.
Voltage vs. Ligand II: Structural insights of the intrinsic flexibility in cyclic nucleotide-gated channels

ABSTRACT In the preceding article, we present a flexibility analysis of the voltage-gated ion channel (VGIC) superfamily. In this study, we describe in detail the flexibility profile of the voltage-sensor domain (VSD) and the pore domain (PD) concerning the evolution of 6TM ion channels. In particular, we highlight the role of flexibility in the emergence of CNG channels and describe a significant level of sequence similarity between the archetypical VSD and the TolQ proteins. A highly flexible S4-like segment exhibiting Lys instead Arg for these membrane proteins is reported. Sequence analysis indicates that, in addition to this S4-like segment, TolQ proteins also show similarity with specific motifs in S2 and S3 from typical V-sensors. Notably, S3 flexibility profiles from typical VSDs and S3-like in TolQ proteins are also similar. Interestingly, TolQ from early divergent prokaryotes are comparatively more flexible than those in modern counterparts or true V-sensors. Regarding the PD, we also found that 2TM K+-channels in early prokaryotes are considerably more flexible than the ones in modern microbes, and such flexibility is comparable to the one present in CNG channels. Voltage dependence is mainly exhibited in prokaryotic CNG channels whose VSD is rigid whereas the eukaryotic CNG channels are considerably more flexible and poorly V-dependent. The implication of the flexibility present in CNG channels, their sensitivity to cyclic nucleotides and the cation selectivity are discussed. Finally, we generated a structural model of the putative cyclic nucleotide-modulated ion channel, which we coined here as AqK, from the thermophilic bacteria Aquifex aeolicus, one of the earliest diverging prokaryotes known. Overall, our analysis suggests that V-sensors in CNG-like channels were essentially rigid in early prokaryotes but raises the possibility that this module was probably part of a very flexible stator protein of the bacterial flagellum motor complex.
Integrating Social Care Into the Delivery of Health Care.

It has long been known that social factors influence health. However, a recent upsurge of interest in addressing social needs within the context of health care delivery has emerged,1-3 driven in part by a recognition that achieving high-quality, high-value health care may require attention to nonmedical factors such as housing, food, and transportation. Addressing social determinants of health may be important for any person during periods of increased need (eg, after discharge from the hospital) and particularly important for addressing health disparities in communities with greater social need. A new report4 from a consensus committee of the National Academies of Sciences, Engineering, and Medicine provides recommendations to guide practice and policy discussions in this area.
Developing assistive robots for people with mild cognitive impairment and mild dementia: a qualitative study with older adults and experts in aged care

Objectives This research is part of an international project to design and test a home-based healthcare robot to help older adults with mild cognitive impairment (MCI) or early dementia. The aim was to investigate the perceived usefulness of different daily-care activities for the robot, developed from previous research on needs. Design Qualitative descriptive analysis using semistructured interviews. Two studies were conducted. In the first study, participants watched videos of a prototype robot performing daily-care activities; in the second study, participants interacted with the robot itself. Setting Interviews were conducted at a university and a retirement village. Participants In study 1, participants were nine experts in aged care and nine older adults living in an aged care facility. In study 2, participants were 10 experts in aged care. Results The themes that emerged included aspects of the robot’s interactions, potential benefits, the appearance, actions and humanness of the robot, ways to improve its functionality and technical issues. Overall, the activities were perceived as useful, especially the reminders and safety checks, with possible benefits of companionship, reassurance and reduced caregiver burden. Suggestions included personalising the robot to each individual, simplifying the language and adding more activities. Technical issues still need to be fixed. Conclusion This study adds to knowledge about healthcare robots for people with MCI by developing and testing a new robot with daily-care activities including safety checks. The robot was seen to be potentially useful but needs to be tested with people with MCI.
Predicting Alzheimer Disease From Mild Cognitive Impairment With a Deep Belief Network Based on 18F-FDG-PET Images

Objective: Accurate diagnosis of early Alzheimer disease (AD) plays a critical role in preventing the progression of memory impairment. We aimed to develop a new deep belief network (DBN) framework using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) metabolic imaging to identify patients at the mild cognitive impairment (MCI) stage with presymptomatic AD and to discriminate them from other patients with MCI. Methods: 18F-fluorodeoxyglucose-PET images of 109 patients recruited in the ongoing longitudinal Alzheimer’s Disease Neuroimaging Initiative study were included in this analysis. Patients were grouped into 2 classes: (1) stable mild cognitive impairment (n = 62) or (2) progressive mild cognitive impairment (n = 47). Our framework is composed of 4 steps: (1) image preprocessing: normalization and smoothing; (2) identification of regions of interest (ROIs); (3) feature learning using deep neural networks; and (4) classification by support vector machine with 3 kernels. All classification experiments were performed with a 5-fold cross-validation. Accuracy, sensitivity, and specificity were used to validate the results. Result: A total of 1103 ROIs were obtained. One hundred features were learned from ROIs using the DBN. The classification accuracy using linear, polynomial, and RBF kernels was 83.9%, 79.2%, and 86.6%, respectively. This method may be a powerful tool for personalized precision medicine in the population with prediction of early AD progression.
Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells

Quiescence is essential for the long-term maintenance of adult stem cells but how stem cells maintain quiescence is poorly understood. Here, we show that neural stem cells (NSCs) in the adult mouse hippocampus actively transcribe the pro-activation factor Ascl1 regardless of their activated or quiescent states. We found that the inhibitor of DNA binding protein Id4 is enriched in quiescent NSCs and that elimination of Id4 results in abnormal accumulation of Ascl1 protein and premature stem cell activation. Accordingly, Id4 and other Id proteins promote elimination of Ascl1 protein in NSC cultures. Id4 sequesters Ascl1 heterodimerization partner E47, promoting Ascl1 protein degradation and stem cell quiescence. Our results highlight the importance of non-transcriptional mechanisms for the maintenance of NSC quiescence and reveal a role for Id4 as a quiescence-inducing factor, in contrast with its role of promoting the proliferation of embryonic neural progenitors.
Chemical Composition and Antimicrobial Activity of Achillea tenuifolia Lam. Essential Oil at Different Phenological Stages from Khoy

Achillea species and in particular Achillea tenuifolia Lam. is generally used as a food flavor and traditional remedies, especially in the initial developmental stage for medical conditions in the Mediterranean part of Iran. In this report, we extracted the essential oil from the aerial parts of A. tenuifolia (collected from Khoy), at various developmental stages (i. e., vegetative, flowering and fruiting), characterized them and studied their antibacterial activities. Of 46, 51 and 38 components found in the vegetative, flowering, and fruiting stages, respectively, 35 were present in all three stages, including oxygenated terpenes such as carvacrol (30.85–34.11), germacrene C (16.21–17.87), spathulenol (7.26–8.96), β‐sesquiphellandrene (4.11–4.25), τ‐muurolol (2.27–3.25) and α‐cadinol (2.01–3.29). We witnessed that the composition of the essential oils varies with phenological stages and geographic regions. The essential oil demonstrated substantial antibacterial properties against both Gram‐positive and Gram‐negative bacteria, indicated by disk method, Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays. Except Pseudomonas aeruginosa, the essential oils of various phenological stages showed higher antibacterial activity against tested bacteria, with Bacillus anthracis as the most sensitive strain. Moreover, although antibacterial characteristics of the essential oil from the vegetative and flowering stages were similar (p=0.91), they were significantly different from those of fruiting stage (p<0.005 in both MIC and MBC tests). This emphasizes the importance of the developmental stage of the plant in the biological properties of its essential oil and justifies the widespread application of this plant in the vegetative stage.
Efficacy of Glutathione for Patients With Cystic Fibrosis: A Meta-analysis of Randomized-Controlled Studies

Introduction The impact of glutathione on pulmonary function remains elusive for patients with cystic fibrosis. The aim of this systematic review and meta-analysis is to explore the influence of glutathione versus placebo on pulmonary function of cystic fibrosis. Methods We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2019, and randomized-controlled trials (RCTs) regarding the effect of glutathione on pulmonary function of cystic fibrosis are included in this meta-analysis. Results Four RCTs are included. Compared with control group in patients with cystic fibrosis, glutathione treatment shows positive impact on forced expiratory volume 1 second (FEV1) (mean difference [MD] = 0.19; 95% confidence interval (CI), 0.10–0.28; P < . 0001) and body mass index (MD = 0.27; 95% CI, 0.02–0.51; P = .03), but has no obvious influence on 6-minute walk test (standard MD = 0.28; 95% CI, −0.08 to 0.64; P = .13), number of exacerbations (MD = −0.10; 95% CI, −0.34 to 0.15; P = .43), abdominal pain or distal intestinal obstruction (risk ratios [RR] = 0.78; 95% CI, 0.32–1.90; P = .58), or hemoptysis (RR = 1.87; 95% CI, 0.43–8.26; P = .41). Conclusions Glutathione treatment provides some benefits to improve pulmonary function of patients with cystic fibrosis, as evidenced by the increase in FEV1.
Practical High-Quality Electrostatic Potential Surfaces for Drug Discovery Using a Graph-Convolutional Deep Neural Network.

Inspecting protein and ligand electrostatic potential (ESP) surfaces in order to optimize electrostatic complementarity is a key activity in drug design. These ESP surfaces need to reflect the true electrostatic nature of the molecules, which typically means time-consuming high-level quantum mechanics (QM) calculations are required. For interactive design much faster alternative methods are required. Here, we present a graph convolutional deep neural network (DNN) model, trained on ESP surfaces derived from high quality QM calculations, that generates ESP surfaces for ligands in a fraction of a second. Additionally, we describe a method for constructing fast QM-trained ESP surfaces for proteins. We show that the DNN model generates ESP surfaces that are in good agreement with QM and that the ESP values correlate well with experimental properties relevant to medicinal chemistry. We believe that these high-quality, interactive ESP surfaces form a powerful tool for driving drug discovery programs forward. The trained model and associated code are available from https://github.com/AstexUK/ESP_DNN .
Prognosis and acute complications at the first onset of idiopathic nephrotic syndrome in children: a nationwide survey in Japan (JP-SHINE study).

BACKGROUND Information on the epidemiology of idiopathic nephrotic syndrome (INS) in children, complications of INS and the side effects of steroid therapy is scarce. METHODS The Japanese Pediatric Survey Holding Information of Nephrotic Syndrome, a nationwide cohort study, was conducted by the Japanese Study Group of Renal Disease in Children and enrolled 2099 children with newly diagnosed INS between 1 January 2010 and 31 December 2012. We conducted a follow-up study of the complications during the first onset and the patients' prognosis in this cohort. RESULTS We obtained follow-up data on 999 children (672 males) with a median age at onset of 4.5 years [interquartile range (IQR) 2.8-9.4] and a median follow-up period of 4.1 years (IQR 2.5-5.1). At the first onset, 24% of patients experienced severe acute kidney injury (AKI), defined as a serum creatinine increase to a level two or more times the baseline. On logistic regression analysis, age, hematuria, severe hypoalbuminemia (serum albumin <1.0 g/dL) and severe bacterial infection were not independent factors, but female sex {hazard ratio [HR] 1.5 [95% confidence interval (CI) 1.1-1.7]} and hypertension [HR 4.0 (95% CI 2.6-6.0)] were significantly related to AKI. During the observation period, ocular hypertension requiring treatment occurred in 17.4% of patients, among which 0.4% received surgical treatment. Progression to frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome in 3 years was seen in 44.2% of the patients and was shown by the Cox regression analysis to be significantly related to younger age and days until remission at the first episode, but not to sex, hematuria, the minimum serum albumin level or AKI. Two patients died during the observation period. One patient showed progression to end-stage kidney disease. CONCLUSION Based on the results of a multicenter questionnaire survey, the overall survival and renal survival rates were found to be excellent. However, proper management of complications, particularly in AKI and ocular hypertension, is mandatory.
Genetic differentiation in functional traits among European sessile oak populations.

The vulnerability of forest species and tree populations to climate change is related to the exposure of the ecosystem to extreme climatic conditions and to the adaptive capacity of the population to cope with those conditions. Adaptive capacity is a relatively under-researched topic within the forest science community and there is an urgent need to understand to what extent particular combinations of traits have been shaped by natural selection under climatic gradients, potentially resulting in adaptive multi-trait associations. Thus, our aim was to quantify genetic variation in several leaf and woody traits that may contribute to multi-trait associations in which intraspecific variation could represent a source for species adaptation to climate change. A multi-trait approach was performed using nine Quercus petraea provenances originating from different locations that cover most of the species' distribution range over Europe and that were grown in a common garden. Multiple adaptive differences were observed between oak provenances but also some evolutionary stasis. Also, our results revealed higher genetic differentiation in traits related to phenology and growth than in those related to xylem anatomy, physiology and hydraulics for which no genetic differentiation was observed. The multiple associations between those traits and climate variables resulting from multivariate and path analyses suggest a multi-trait association largely involving phenological and growth traits for Quercus petraea.
Effects of Huangkui Capsule on the Expression of SPARC in the Kidney Tissue of a Rat Model with Diabetic Nephropathy.

OBJECTIVE The objective of the research is to investigate the effects of Huangkui capsule on the expression of SPARC in the kidney tissues of diabetic nephropathy. METHODS SD rats were divided into three groups: normal control group, untreated DN group and HKC-treated DN group. The therapeutic effects and underlying molecular mechanism of HKC on DN rats induced by streptozotocin were evaluated by the levels of serum creatinine, blood urea nitrogen, 24-hour urinary protein and the expression of SPARC. Pathological changes of kidney tissues were observed through hematoxylin-eosin (HE) staining. Moreover, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to detect the variation of SPARC. RESULTS This study was performed to investigate the effects of HKC on DN in SD rats model and its molecular mechanism. Our results showed that, the rats treated with HKC had an improved general state and reduced creatinine, blood urea nitrogen and 24-hour urinary protein levels. The deterioration of renal function was delayed due to treatment with HKC. We utilized HE staining to observe that HKC can improve histopathological findings in the kidney tissues of DN rats, including kidney fibrosis. Results of western blot and qRT-PCR showed that HKC can inhibit the expressions of SPARC in the rat model of DN.
Aging Brain: In Search of Better Neurotherapeutics.

During the past 25 years, international meetings organized every second year by the pharmacologists of the University of Calabria have represented an awaited appointment largely participated by young scientists to discuss basic and clinical research concerned with hot topics in biomedicine. This year, high caliber international scientists met on May 4-5, 2017 with young researchers at the Club of the University of Calabria (Cosenza, Italy) in order to make the point on neurodegenerative diseases, affecting mainly the aging brain and also to share emerging strategies for a better therapeutic management of these diseases. Participants from USA, Germany, Russia, Japan, England, Serbia and Italy created a friendly atmosphere that allowed a lively and open discussion making the meeting a success. The beauty of the Norman-Swabian Castle of Byzantine origin (a.d. 937) of Cosenza, the Civic Museum of the Byzantine Icons and Traditions of Frascineto (CS) and the hospitality of Altomonte (CS) made the rest.