Miracle-dz/UniFAR-FTUs huggingface dataset:
In the Literature.

TARIQ SALEEM, Department of Palliative Care, Policy & Rehabilitation, King's College London, P. NIGEL LEIGH, Department of Clinical Neuroscience, King's College London, IRENE J. HIGGINSON, Department of Palliative Care, Policy & Rehabilitation, King's College London, School of Medicine, London, UK Symptom Prevalence Among People Affected by Advanced and Progressive Neurological Conditions-a Systematic Review
The activation of cardiac dSir2-related pathways mediates physical exercise resistance to heart aging in old Drosophila

Cardiac aging is majorly characterized by increased diastolic dysfunction, lipid accumulation, oxidative stress, and contractility debility. The Sir2/Sirt1 gene overexpression delays cell aging and reduces obesity and oxidative stress. Exercise improves heart function and delays heart aging. However, it remains unclear whether exercise delaying heart aging is related to cardiac Sir2/Sirt1-related pathways. In this study, cardiac dSir2 overexpression or knockdown was regulated using the UAS/hand-Gal4 system in Drosophila. Flies underwent exercise interventions from 4 weeks to 5 weeks old. Results showed that either cardiac dSir2 overexpression or exercise remarkably increased the cardiac period, systolic interval, diastolic interval, fractional shortening, SOD activity, dSIR2 protein, Foxo, dSir2, Nmnat, and bmm expression levels in the aging flies; they also notably reduced the cardiac triacylglycerol level, malonaldehyde level, and the diastolic dysfunction index. Either cardiac dSir2 knockdown or aging had almost opposite effects on the heart as those of cardiac dSir2 overexpression. Therefore, we claim that cardiac dSir2 overexpression or knockdown delayed or promoted heart aging by reducing or increasing age-related oxidative stress, lipid accumulation, diastolic dysfunction, and contractility debility. The activation of cardiac dSir2/Foxo/SOD and dSir2/Foxo/bmm pathways may be two important molecular mechanisms through which exercise works against heart aging in Drosophila.
Optimizing chronic slow breathing training to cause a therapeutic effect on heart rate variability

OPTIMIZING CHRONIC SLOW BREATHING TRAINING TO CAUSE A THERAPEUTIC EFFECT ON HEART RATE VARIABILITY Jennifer Joy Brown Old Dominion University, 2012 Director: Dr. David P. Swain Heart rate variability (HRV) is a valid and reliable tool that can be used to determine the basic state of an individual's autonomic health. The current study attempted to establish the minimum frequency of breathing practice necessary to produce a therapeutic effect on HRV over the course of a four-week period with four different treatment groups, specifically, groups that practiced a slow breathing protocol for either 2, 3 or 5 times per week, and a control group. Forty-three subjects (14 males, 29 females), ages 18 50 years, were screened, pre-tested, matched for sex, age and HRV, assigned to a specific group for a four-week training period, and completed the study. All preand post-test measurements were made during a 10-minute period of supine rest, and included systolic and diastolic blood pressure (BP), heart rate (HR), and the following HRV measures: standard deviation of the normal to normal R waves (SDNN), root mean square of successive differences (RMSSD), high frequency power (HF), low frequency power (LF), and HF/LF ratio. During the 4-week training period, subjects kept a log of their breathing training and then returned for post-testing of the same variables. A two-way analysis of variance with repeated measures on one factor and post hoc T-tests were used to evaluate the data. Significance was set at the 0.05 level. Following the 4-week training period, the control group experienced an increase in systolic BP, while all three training groups experienced a decrease. For diastolic BP, the control group experienced an increase, while only the 2 times per week training group experienced a decrease. For HR, the 2 times per week and 5 times per week groups demonstrated a decrease, while no other groups changed. There were no differences in any HRV measures as a result of training in any group. In conclusion, although previous research had found that breathing training affected HRV measures, there was no effect in this study regardless of the frequency of training. Breathing training did cause a reduction in resting BP and heart rate, but the frequency of training had little to no differential effect. The study was unable to demonstrate a minimum frequency of breathing training for affecting the autonomic nervous system.
Relationship between skeletal Class II and Class III malocclusions with vertical skeletal pattern

ABSTRACT Objective: The purpose of this study was to establish the association between sagittal and vertical skeletal patterns and assess which cephalometric variables contribute to the possibility of developing skeletal Class II or Class III malocclusion. Methods: Cross-sectional study. The sample included pre-treatment lateral cephalogram radiographs from 548 subjects (325 female, 223 male) aged 18 to 66 years. Sagittal skeletal pattern was established by three different classification parameters (ANB angle, Wits and App-Bpp) and vertical skeletal pattern by SN-Mandibular plane angle. Cephalometric variables were measured using Dolphin software (Imaging and Management Solutions, Chatsworth, Calif, USA) by a previously calibrated operator. The statistical analysis was carried out with Chi-square test, ANOVA/Kruskal-Wallis test, and an ordinal multinomial regression model. Results: Evidence of association (p< 0.05) between sagittal and vertical skeletal patterns was found with a greater proportion of hyperdivergent skeletal pattern in Class II malocclusion using three parameters to assess the vertical pattern, and there was more prevalent hypodivergence in Class III malocclusion, considering ANB and App-Bpp measurements. Subjects with hyperdivergent skeletal pattern (odds ratio [OR]=1.85-3.65), maxillary prognathism (OR=2.67-24.88) and mandibular retrognathism (OR=2.57-22.65) had a significantly (p< 0.05) greater chance of developing skeletal Class II malocclusion. Meanwhile, subjects with maxillary retrognathism (OR=2.76-100.59) and mandibular prognathism (OR=5.92-21.50) had a significantly (p< 0.05) greater chance of developing skeletal Class III malocclusion. Conclusions: A relationship was found between Class II and Class III malocclusion with the vertical skeletal pattern. There is a tendency toward skeletal compensation with both vertical and sagittal malocclusions.
Factors Associated with Bed-Blocking at a University Hospital (Cantabria, Spain) between 2007 and 2015: A Retrospective Observational Study

Current studies on bed-blocking or delayed discharge for non-medical reasons report important variations depending on the country or setting under study. Research on this subject is clearly important as the current system reveals major inefficiencies. Although there is some agreement on the patient-related factors that contribute to the phenomenon, such as older age or a lack of functional ability, there is greater variability regarding environmental or organizational factors. This study sought to quantify the number of cases and days inappropriately spent in hospital and identify patient characteristics and healthcare service use associated with the total length of stay. All cases of delayed discharge were studied at the hospitalization units of a general university hospital in Northern Spain between 2007 and 2015. According to regression estimates, the following characteristics were related to a longer stay: higher complexity through (Diagnosis-Related Group) DRG weight, a diagnosis that implied a lack of functional ability, surgical treatment, having to wait for a destination upon final discharge or return home. After an initial increase, a reduction in delayed discharge was observed, which was maintained for the duration of the study period. Multi-component interventions related with discharge planning can favor a reduced inefficiency with fewer unnecessary stays.
Prematurity blunts the feeding-induced stimulation of translation initiation signaling and protein synthesis in muscle of neonatal piglets.

Postnatal growth of lean mass is commonly blunted in preterm infants and may contribute to short- and long-term morbidities. To determine whether preterm birth alters the protein anabolic response to feeding, piglets were delivered at term or preterm and fractional protein synthesis rates (Ks) measured at 3 d of age while fasted or after an enteral elemental meal. Activation of signaling pathways that regulate protein synthesis and degradation were determined. Relative body weight gain was lower in preterm than term pigs. Gestational age at birth (GAB) did not alter fasting plasma glucose or insulin, but when fed, plasma insulin and glucose rose more slowly, and reached peak value later, in preterm than term. Feeding increased Ks in longissimus dorsi (LD) and gastrocnemius muscles, heart, pancreas, and kidney in both GAB groups, but the response was blunted in preterms. In diaphragm, lung, jejunum, and brain, feeding increased Ks regardless of GAB. Liver Ks was greater in preterm than term and increased with feeding regardless of GAB. In all tissues, phosphorylation of 4EBP1, S6K1, and PKB directly mirrored Ks. In LD, eIF4E∙eIF4G complex formation, phosphorylation of TSC2, mTOR, and rpS6, and association of mTOR with RagA, RagC, and Rheb were increased by feeding and blunted by prematurity. There were no differences among groups in protein degradation markers in LD. In summary, preterm pigs exhibit decreased weight gain and feeding-induced protein synthesis in muscles, pancreas, and kidney compared to term piglets, which was associated with blunted insulin- and/or amino acid-induced translation initiation signaling.
A novel machine learning-derived radiotranscriptomic signature of perivascular fat improves cardiac risk prediction using coronary CT angiography

Abstract Background Coronary inflammation induces dynamic changes in the balance between water and lipid content in perivascular adipose tissue (PVAT), as captured by perivascular Fat Attenuation Index (FAI) in standard coronary CT angiography (CCTA). However, inflammation is not the only process involved in atherogenesis and we hypothesized that additional radiomic signatures of adverse fibrotic and microvascular PVAT remodelling, may further improve cardiac risk prediction. Methods and results We present a new artificial intelligence-powered method to predict cardiac risk by analysing the radiomic profile of coronary PVAT, developed and validated in patient cohorts acquired in three different studies. In Study 1, adipose tissue biopsies were obtained from 167 patients undergoing cardiac surgery, and the expression of genes representing inflammation, fibrosis and vascularity was linked with the radiomic features extracted from tissue CT images. Adipose tissue wavelet-transformed mean attenuation (captured by FAI) was the most sensitive radiomic feature in describing tissue inflammation (TNFA expression), while features of radiomic texture were related to adipose tissue fibrosis (COL1A1 expression) and vascularity (CD31 expression). In Study 2, we analysed 1391 coronary PVAT radiomic features in 101 patients who experienced major adverse cardiac events (MACE) within 5 years of having a CCTA and 101 matched controls, training and validating a machine learning (random forest) algorithm (fat radiomic profile, FRP) to discriminate cases from controls (C-statistic 0.77 [95%CI: 0.62–0.93] in the external validation set). The coronary FRP signature was then tested in 1575 consecutive eligible participants in the SCOT-HEART trial, where it significantly improved MACE prediction beyond traditional risk stratification that included risk factors, coronary calcium score, coronary stenosis, and high-risk plaque features on CCTA (Δ[C-statistic] = 0.126, P < 0.001). In Study 3, FRP was significantly higher in 44 patients presenting with acute myocardial infarction compared with 44 matched controls, but unlike FAI, remained unchanged 6 months after the index event, confirming that FRP detects persistent PVAT changes not captured by FAI. Conclusion The CCTA-based radiomic profiling of coronary artery PVAT detects perivascular structural remodelling associated with coronary artery disease, beyond inflammation. A new artificial intelligence (AI)-powered imaging biomarker (FRP) leads to a striking improvement of cardiac risk prediction over and above the current state-of-the-art.
Differences in blastomere totipotency in 2-cell mouse embryos are a maternal trait mediated by asymmetric mRNA distribution

Abstract It is widely held that the first two blastomeres of mammalian embryos are equally totipotent and that this totipotency belongs to the group of regulative properties. However, this interpretation neglects an important aspect: evidence only came from successful monozygotic twins which can speak only for those pairs of half-embryos that are able to regulate in the first place. Are the frequently occurring incomplete pairs simply an artefact, or do they represent a real difference, be it in the imperfect blastomere’s ability to regulate growth or in the distribution of any compound X that constrains regulation? Using the model system of mouse embryos bisected at the 2-cell stage after fertilization, we present evidence that the interblastomere differences evade regulation by external factors and are already latent in oocytes. Specifically, an interblastomere imbalance of epiblast production persists under the most diverse culture conditions and applies to the same extent in parthenogenetic counterparts. As a result, cases in which twin blastocysts continued to develop in only one member account for 65 and 57% of zygotic and parthenogenetic pairs, respectively. The interblastomere imbalance is related to the subcellular distribution of gene products, as documented for the epiblast-related gene Cops3, using mRNA FISH in super-resolution mode confocal microscopy. Blastomere patterns of Cops3 mRNA distribution are α-amanitin-resistant. Thus, the imbalance originates not from de novo transcription, but from influences which are effective before fertilisation. These data expose previously unrecognized limits of regulative capacities of 2-cell stage blastomeres and point to aspects of cytoplasmic organization of the mouse oocyte that segregate unequally to blastomeres during cleavage.
Post-Traumatic Stress Disorder Chronification via Monoaminooxidase and Cortisol Metabolism

Affiliations 1 School of Medical Biology, South Ural State University, Chelyabinsk, Russia 2 Institute of Molecular Physiology and Genetics, Centre for Biosciences, Slovak Academy of Sciences, Bratislava, Slovak Republic 3 Laboratory for Regulatory Mechanisms of Stress and Adaptation, Institute of General Pathology and Pathophysiology, Moscow, Russia 4 Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas, USA 5 Department of Medicine, Technical University of Dresden, Dresden, Germany 6 Rayne Institute, Division of Diabetes & Nutritional Sciences, Endocrinology and Diabetes, Faculty of Life Sciences & Medicine, Kings College London, London, UK 7 College of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA 8 ICAHN School of Medicine at Mount Sinai, New York, NY, USA 9 Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University of Leipzig, Leipzig, Germany 10 Department of Psychiatry, Flinders University School of Medicine, Bedford Park, SA, Australia 11 Department of Psychiatry, University of Adelaide School of Medicine, Bedford Park, SA, Australia 12 Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic
The Effect of Age, Gender and Body Mass Index on Tear Film Neuromediators and Corneal Nerves

ABSTRACT Purpose: To evaluate the effect of age, gender and body mass index (BMI) on the levels of tear film neuromediators and corneal nerve parameters in healthy individuals. Methods: Twenty-six healthy subjects were screened for any neurological deficits. The concentration of substance P and calcitonin gene-related peptide (CGRP) in tears was measured by enzyme-linked immunosorbent assay. Corneal nerve fibers were imaged using confocal microscopy and assessed by automated image analysis software. ﻿Associations between the clinical variables were analyzed using Pearson or Spearman correlation. Univariate general linear regression was performed to examine the independent relationship between age, BMI and gender of the subjects with concentrations of substance P, CGRP and corneal nerve fiber parameters. Results: Fifteen (58%) of the study participants were male. The mean age of the study cohort was 36 ± 12 years (range, 21–59) with an average BMI of 25 ± 4 kg/m2. The median [IQR] concentrations of substance P and CGRP was 715 [372–1463] pg/mL and 38 [15–74] ng/mL respectively. Moderate but significant positive correlations were found between the concentration of substance P and corneal nerve fiber density (r = 0.467, P = .016), nerve fiber length (r = 0.528, P = .006) and nerve fractal dimension (rs = 0.614, P = .002). There was a significant age-dependent reduction in the concentration of substance P (−6% pg/mL per year, P = .001) and CGRP (−8% ng/ml per year, P < .001). Corneal nerve fiber density (−0.171 no./mm2 per year, P = .029) and nerve fractal dimension (−0.001 per year, P = .021) showed reductions with advancing age. Gender and BMI did not influence any of the measurements. Conclusions: The concentrations of substance P and CGRP in tears, as well as corneal nerve fiber density and nerve fractal dimension, are significantly reduced with advancing age. ﻿Age should be considered when evaluating patients for diagnosis and follow-up of corneal neuropathy or ocular surface disorders.
The Kinematics of Breasts Implanted With a Reduced Mass Implant: A Pilot Study.

BACKGROUND Breast implants may increase breast skin tension and interact with surrounding tissues to alter breast position and motion during dynamic activity. Reducing implant mass and changing implant location (submuscular/subglandular), may also affect breast kinematics and the subsequent load on breast structures. OBJECTIVES This pilot study aims to describe the kinematics of breasts augmented with reduced mass implants during standing, walking and running, compared to natural breasts, and to provide insight into how implant location (submuscular/subglandular) alters breast kinematics. METHODS 12-15 months post-surgery, two breast augmentation participants (32AA pre-surgery, anatomical submuscular 255 cc B-Lite® reduced mass implant, and 32A pre-surgery, anatomical subglandular 285 cc B-Lite® reduced mass implant) and two natural breasted participants of similar breast size and anthropometrics were recruited (Natural 1 and 2). Nipple and torso positional data were recorded using electromagnetic sensors during standing, walking and running. Nipple kinematics relative to the torso were calculated. RESULTS The B-Lite® participants both displayed greater nipple projection and elevation during standing and a 50% reduction in nipple acceleration during walking, when compared to their natural counterparts. During running, the B-Lite® subglandular participant displayed decreased nipple kinematics, compared to their natural counterpart and lower nipple kinematics compared to the B-Lite® submuscular participant during walking and running. CONCLUSION A combination of implant location (subglandular) and reduced mass minimised nipple kinematics during running. Reducing nipple kinematics during dynamic activity may decrease the loading on breast structures, helping to decrease ptosis and increase longevity of procedure outcomes.
Prevalence of self-reported dengue infections in Manaus Metropolitan Region: a cross-sectional study.

INTRODUCTION Dengue is an endemic and epidemic disease in Brazil, with a high burden of disease. Amazonas State has a high risk of transmission. This study aimed to assess the self-reported prevalence of dengue in adults living in Manaus Metropolitan Region. METHODS A cross-sectional study was conducted with adults living in Manaus Metropolitan Region in 2015. We performed a three-phase probabilistic sampling to collect participants' clinical and sociodemographic data. Self-reported dengue infection in the previous year was the primary outcome. Descriptive statistics and Poisson regression analysis with robust variance were used to calculate the prevalence ratio (PR) of dengue infections with 95% confidence intervals (95% CIs). Multilevel analysis including city and neighborhood variables was calculated. All analyses considered the complex sampling. RESULTS Among the 4,001 participants, dengue in the previous year was self-reported by 7.0% (95% CI 6.3%-7.8%). Dengue was more frequent in women(PR 1.51; 95% CI 1.06-2.13), elderly participants (≥60 years old, PR 2.54; 95% CI 1.19-5.45), White and Asian participants (PR, 1.57; 95% CI, 1.11-2.23), and individuals who had not received endemic agent visits (PR, 2.28; 95% CI, 1.31-3.99). After multilevel analysis, sex was no longer a significant variable, with the remaining associations still significant. CONCLUSIONS Seven out of 100 inhabitants of Manaus Metropolitan Region reported dengue in the previous year. Dengue was predominantly observed in women, elderly individuals, White and Asian individuals, and individuals who did not receive endemic agent visits. The setting plays an important role in dengue infections.
Paracrine Crosstalk between Intestinal L- and D-cells Controls Secretion of Glucagon-Like Peptide-1 in mice.

DPP-4 inhibitors, used for treatment of type 2 diabetes, act by increasing the concentrations of intact GLP-1 but at the same time they inhibit secretion of GLP-1, perhaps by a negative feed-back mechanism. We hypothesized that GLP-1 secretion is feed-back regulated by somatostatin from neighbouring D-cells, and blocking this feed-back circuit results in increased GLP-1 secretion. We used a wide range of experimental techniques including gene expression analysis, immunohistochemical approaches and the perfused mouse intestine to characterise the paracrine circuit controlling GLP-1 and somatostatin. We show that 1) antagonising the SSTr2 and SSTr5 led to increased GLP-1 and somatostatin secretion in the mouse, 2) that SS exhibits strong tonic inhibition of GLP-1 secretion preferentially through SSTr5 and 3) that the secretion of somatostatin was GLP-1 receptor dependent. We conclude that SS is a tonic inhibitor of GLP-1 secretion and interventions in the somatostain-GLP-1 paracrine loop leads to increased GLP-1 secretion.
A protein architecture guided screen for modification dependent restriction endonucleases

Abstract Modification dependent restriction endonucleases (MDREs) often have separate catalytic and modification dependent domains. We systematically looked for previously uncharacterized fusion proteins featuring a PUA or DUF3427 domain and HNH or PD-(D/E)XK catalytic domain. The enzymes were clustered by similarity of their putative modification sensing domains into several groups. The TspA15I (VcaM4I, CmeDI), ScoA3IV (MsiJI, VcaCI) and YenY4I groups, all featuring a PUA superfamily domain, preferentially cleaved DNA containing 5-methylcytosine or 5-hydroxymethylcytosine. ScoA3V, also featuring a PUA superfamily domain, but of a different clade, exhibited 6-methyladenine stimulated nicking activity. With few exceptions, ORFs for PUA-superfamily domain containing endonucleases were not close to DNA methyltransferase ORFs, strongly supporting modification dependent activity of the endonucleases. DUF3427 domain containing fusion proteins had very little or no endonuclease activity, despite the presence of a putative PD-(D/E)XK catalytic domain. However, their expression potently restricted phage T4gt in Escherichia coli cells. In contrast to the ORFs for PUA domain containing endonucleases, the ORFs for DUF3427 fusion proteins were frequently found in defense islands, often also featuring DNA methyltransferases.