Miracle-dz/UniFAR-FTUs huggingface dataset:
Local guidelines for admission to UK midwifery units compared with national guidance: A national survey using the UK Midwifery Study System (UKMidSS)

Objectives To describe the extent to which local guidelines for admission to UK midwifery units align with national guidance; to describe variation in individual admission criteria; and to describe the extent to which alongside midwifery units (AMUs) are the default option for eligible women. Design National cross-sectional survey. Setting All 122 UK maternity services with midwifery units, between October 2018 and February 2019. Outcome measures Alignment of local admission guidelines with national guidance (NICE CG190); frequency and nature of variation in individual admission criteria; percentage of services with AMU as default birth setting for eligible women. Results Admission guidelines were received from 87 maternity services (71%), representing 153 units, and we analysed 85 individual guideline documents. Overall, 92% of local admission guidelines varied from national guidance; 76% contained both some admission criteria that were ‘more inclusive’ and some that were ‘more restrictive’ than national guidance. The most common ‘more inclusive’ admission criteria, occurring in 40–80% of guidelines, were: explicit admission of women with parity ≥4; aged 35-40yrs; with a BMI 30-35kg/m2; selective admission of women with a BMI 35-40kg/m2; Group B Streptococcus carriers; and those undergoing induction of labour. The most common ‘more restrictive’ admission criteria, occurring in around 30% of guidelines, excluded women who: declined blood products; had experienced female genital cutting; were aged <16yrs; or had not attended for regular antenatal care. Over half of services (59%) reported the AMU as the default option for healthy women with straightforward pregnancies. Conclusions The variation in local midwifery unit admission criteria found in this study represents a potentially confusing and inequitable basis for women making choices about planned place of birth. A review of national guidance may be indicated and where a lack of relevant evidence underlies variation in admission criteria, further research by planned place of birth is required.
Towards New Diagnostic Approaches in Disorders of Consciousness: A Proof of Concept Study on the Promising Use of Imagery Visuomotor Task

Background: advanced paraclinical approaches using functional neuroimaging and electroencephalography (EEG) allow identifying patients who are covertly aware despite being diagnosed as unresponsive wakefulness syndrome (UWS). Bedside detection of covert awareness employing motor imagery tasks (MI), which is a universally accepted clinical indicator of awareness in the absence of overt behavior, may miss some of these patients, as they could still have a certain level of awareness. We aimed at assessing covert awareness in patients with UWS using a visuomotor-guided motor imagery task (VMI) during EEG recording. Methods: nine patients in a minimally conscious state (MCS), 11 patients in a UWS, and 15 healthy individuals (control group—CG) were provided with an VMI (imagine dancing while watching a group dance video to command), a simple-MI (imagine squeezing their right hand to command), and an advanced-MI (imagine dancing without watching a group dance video to command) to detect command-following. We analyzed the command-specific EEG responses (event-related synchronization/desynchronization—ERS/ERD) of each patient, assessing whether these responses were appropriate, consistent, and statistically similar to those elicited in the CG, as reliable markers of motor imagery. Results: All patients in MCS, all healthy individuals and one patient in UWS repeatedly and reliably generated appropriate EEG responses to distinct commands of motor imagery with a classification accuracy of 60–80%. Conclusions: VMI outperformed significantly MI tasks. Therefore, patients in UWS may be still misdiagnosed despite a rigorous clinical assessment and an appropriate MI assessment. It is thus possible to suggest that motor imagery tasks should be delivered to patients with chronic disorders of consciousness in visuomotor-aided modality (also in the rehabilitation setting) to greatly entrain patient’s participation. In this regard, the EEG approach we described has the clear advantage of being cheap, portable, widely available, and objective. It may be thus considered as, at least, a screening tool to identify the patients who deserve further, advanced paraclinical approaches.
Assessing Impact of HPV Vaccination on Cervical Cancer Incidence among Women Aged 15–29 Years in the United States, 1999–2017: An Ecologic Study

Background: To date, the impact of the human papillomavirus (HPV) vaccine on invasive cervical cancers in the United States has not been documented due, in part, to the time needed for cancer to develop and to recent changes to cervical cancer screening guidelines and recommendations, which complicate data interpretation. Methods: We examined incidence rates of cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) among women aged 15–29 years diagnosed during 1999–2017 using population-based cancer registry data covering 97.8% of the U.S. population. Trends were stratified by age and histology. The annual percent change in cervical cancer incidence per year was calculated using joinpoint regression. Results: During 1999–2017, SCC rates decreased 12.7% per year among women aged 15–20 years, 5.5% among women aged 21–24 years, and 2.3% among women aged 25–29 years. The declines in SCC rates were largest among women aged 15–20 years during 2010–2017, with a decrease of 22.5% per year. Overall, AC rates decreased 4.1% per year among women aged 15–20 years, 3.6% per year among women aged 21–24 years, and 1.6% per year among women aged 25–29 years. AC rates declined the most among women aged 15–20 years during 2006–2017, decreasing 9.4% per year. Conclusions: Since HPV vaccine introduction, both SCC and AC incidence rates declined among women aged 15–20 years, a group not typically screened for cervical cancer, which may suggest HPV vaccine impact. Impact: Timely vaccination and improved screening and follow-up among recommended age groups could result in further reductions in invasive cervical cancer.
Potential Beneficial Effects of Extra Virgin Olive Oils Characterized by High Content in Minor Polar Compounds in Nephropathic Patients: A Pilot Study

Extra virgin olive oil (EVOO) is a lipid food, which constitutes a pillar of the Mediterranean diet. A high number of scientific data have demonstrated that it exerts a variety of beneficial effects on human health due to its peculiar chemical composition including fatty acids (98–99%) and other active compounds even if found in a very low percentage (1–2%). Among them, minor polar compounds (MCPs), represented mainly by phenolic compounds, are relevant for their healthy properties, as stated by the European Food Safety Authority’s (EFSA) claims. In this paper, we described the results obtained from a pilot in vivo study, focused for the first time on the evaluation of the possible beneficial effects of two EVOOs on chronic kidney disease (CKD) patients after the consumption of 40 mL per day for 9 weeks. The selected EVOOs, traced in the production chain, and characterized by High-Performance Liquid Chromatography (HPLC-DAD-MS) analysis, resulted rich in MCPs and satisfied the EFSA’s claim for their content of hydroxytyrosol and derivatives. The results obtained by this in vivo study appear to highlight the potential beneficial role in CKD patients of these EVOOs and are promising for future studies.
Retinoic Acid Sensitivity of Triple-Negative Breast Cancer Cells Characterized by Constitutive Activation of the notch1 Pathway: The Role of Rarβ

Simple Summary We provide experimental evidence that the rare subgroup of triple-negative breast cancer characterized by constitutive activation of the NOTCH1 signaling pathway is sensitive to the anti-tumor action of all-trans retinoic acid, the active metabolite of vitamin A. In this tumor context, all-trans retinoic acid exerts not only an effective action on its own, but it also stimulates the inhibitory activity of γ-secretase inhibitors, a series of therapeutic agents targeting NOTCH1, on cancer cell growth. From a basic and mechanistic standpoint, an important result of the study regards the specific involvement of the retinoid receptor RARβ in the anti-tumor action exerted by all-trans retinoic acid in sensitive triple-negative breast cancer cells. From an applicative point of view the study represents the basis for the design of clinical trials on the efficacy of combinations between all-trans retinoic acid and γ-secretase inhibitors in the treatment of patients affected by a specific subtype of triple-negative breast cancer. Abstract Triple-negative breast cancer (TNBC) is a heterogeneous disease that lacks effective therapeutic options. In this study, we profile eighteen TNBC cell lines for their sensitivity to the anti-proliferative action of all-trans retinoic acid (ATRA). The only three cell lines (HCC-1599, MB-157 and MDA-MB-157) endowed with ATRA-sensitivity are characterized by genetic aberrations of the NOTCH1-gene, causing constitutive activation of the NOTCH1 γ-secretase product, N1ICD. N1ICD renders HCC-1599, MB-157 and MDA-MB-157 cells sensitive not only to ATRA, but also to γ-secretase inhibitors (DAPT; PF-03084014). Combinations of ATRA and γ-secretase inhibitors produce additive/synergistic effects in vitro and in vivo. RNA-sequencing studies of HCC-1599 and MB-157 cells exposed to ATRA and DAPT and ATRA+DAPT demonstrate that the two compounds act on common gene sets, some of which belong to the NOTCH1 pathway. ATRA inhibits the growth of HCC-1599, MB-157 and MDA-MB-157 cells via RARα, which up-regulates several retinoid target-genes, including RARβ. RARβ is a key determinant of ATRA anti-proliferative activity, as its silencing suppresses the effects exerted by the retinoid. In conclusion, we demonstrate that ATRA exerts a significant anti-tumor action only in TNBC cells showing constitutive NOTCH1 activation. Our results support the design of clinical trials involving combinations between ATRA and γ-secretase inhibitors for the treatment of this TNBC subtype.
Chronic Baseline Prostate Inflammation is Associated with Lower Tumor Grade in Men with Prostate Cancer on Repeat Biopsy: Results from the REDUCE Study.

PURPOSE We investigated whether baseline acute or chronic prostate inflammation among men with initial negative biopsies for prostate cancer (PCa) was associated with cancer-grade in 2-year repeat biopsies. MATERIALS AND METHODS Retrospective analyses were conducted of 889 men aged 50-75 years-old with negative baseline prostate biopsy and 2-year repeat biopsy positive for PCa in the Reduction by Dutasteride of PCa Events (REDUCE) study. Acute and chronic prostate inflammation and cancer-grade were determined by central pathology during the REDUCE study. The association of inflammation in baseline and 2-year repeat biopsy and PCa grade in 2-year repeat biopsy was evaluated with Student's t test, chi-squared test and multivariable logistic regression. RESULTS Chronic, acute inflammation and both were detected in 533 (60%), 12 (1%) and 85 (10%) baseline biopsies, respectively. Presence of acute and chronic inflammation were significantly associated with each other (p <0.001). Both types of inflammation were unrelated to race, body mass index, prostate-specific antigen or digital rectal exam. At the 2-year biopsy, 621 (70%) tumors were low-grade (Gleason scores 2-6) and 268 (30%) were high-grade (Gleason scores 7-10). In uni- and multivariable analyses, men with baseline chronic inflammation had significantly less high-grade tumors (univariable odds ratio [OR]=0.64, 95% confidence interval [CI]=0.47-0.87, p=0.004; multivariable OR=0.68, 95% CI=0.50-0.93, p=0.016) than those without baseline chronic inflammation. Baseline acute inflammation was not associated with tumor grade (univariable OR=0.74, 95% CI=0.45-1.20, p=0.22; multivariable OR=0.78, 95% CI=0.48-1.29, p=0.34). CONCLUSIONS Chronic inflammation in a negative biopsy was associated with lower PCa grade among men with cancer on follow-up 2-year biopsy.
Gene Duplication and Fusion: Strategy for Active Site Control and Starting Point for New Catalysts

iv Acknowledgments . vi CHAPTER ONE . 1 1.1 Hydrogen peroxide and its scavengers in cells . 2 1.2 Typical (i.e., monofunctional) catalases . 3 1.3 Peroxidases . 6 1.4 Catalase-peroxidases (KatGs) . 40 CHAPTER TWO . 54 2.
Preferential demethylation of DNA cytosine on the chromosomes restricted to germ cells in the spermatocytes but not the spermatogonia in the inshore hagfish, Eptatretus burgeri

Chromosome elimination and chromatin diminution occur in various species including single-cell ciliates and several multicellular animals. DNA methylcytosine (5mC) and histone modifications have been identified as markers of the eliminated DNA and chromatins in ciliate and finch. Here we examined the levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC; an intermediate of active DNA demethylation) in the male testicular cells of the inshore hagfish Eptatretus burgeri and simultaneously detected germline-restricted repetitive sequences (EEEb1) to identify the chromosomes restricted to germ cells (E-chromosomes). We detected 5mC and 5hmC signals at all chromosomes in the spermatogonia and in all of the interphase nuclei whereas 5mC signals were selectively located on the chromosomes without EEEb1 signals in the spermatocytes’ metaphase, suggesting no 5mC signal on the E-chromosomes. No significant difference in 5hmC levels between the E-chromosomes and the other chromosomes, was detected in the spermatocytes. This chromosome-specific hypomethylation has never been detected in mouse or zebrafish germ cells. These results therefore suggest that the DNA methylation pattern of the E-chromosomes, namely those presumptively eliminated in somatic differentiation, are altered just before or during meiosis. This exclusive alteration of the methylation pattern may play a key role in the chromosome elimination in hagfish species’ embryogenesis.
A Machine Learning Approach for Human Activity Recognition

Human Activity Recognition (HAR) is becoming a significant issue in modern times and directly impact the field of mobile health. Therefore, it is essential the designing of systems which are capable of recognizing properly the activities conducted by the individuals. In this work, we developed a system using the Internet of Things (IoT) and machine learning technologies in order to monitor and assist individuals in their daily life. We compared the data collected using a mobile application and a wearable device with built-in sensors (accelerometer and gyroscope) with the data of a publicly available dataset. By this way, we were able to validate our results and also investigate the functionality and applicability of the wearable device that we choose for the Human Activity Recognition problem. The classification results for the different types of activities presented using our dataset (99%) outperforms the results from the publicly database (97%).
Low-Volume Sprint Interval Swimming Is Sufficient to Increase Blood Metabolic Biomarkers in Master Swimmers

ABSTRACT Purpose: Sprint interval exercise is a time-efficient way of inducing beneficial adaptations. However, little is known about its minimal effective volume, especially in swimming. The aim of the present study was to evaluate and compare the effects of two sprint interval swimming sets of different low volumes on blood biomarkers. Method: Twenty-one master swimmers [11 females aged 38.5 (8.5) years, 10 males aged 42.7 (5.7) years] completed two freestyle swimming sets of 4 × 50 m and 4 × 25 m at maximal intensity and a work-to-rest ratio of 1:1, on different days, in random and counterbalanced order. Blood samples were taken before, immediately after and one hour after exercise for determination of a number of biochemical parameters. Results: Swimming speed was higher in the 4 × 25-m set. Lactate, glucose, insulin, glucagon, cortisol, and reduced glutathione increased immediately post-exercise, while uric acid increased 1 h post-exercise (p < .05). All aforementioned biomarkers, excluding glucagon, increased more with the 4 × 50-m set, compared to the 4 × 25-m set (p < .05). Session rating of perceived exertion was higher after the 4 × 50-m set (p = .011). Conclusion: Both sprint interval swimming sets elicited increases in blood biomarkers in master swimmers. The set of higher volume elicited greater increases in most of the biochemical markers studied but also in subjective load. Thus, although the set of higher volume was more efficient in perturbing blood biomarkers, even the very low-volume set induced metabolic stress that may trigger adaptive mechanisms.
Current challenges in the pathophysiology, diagnosis, and treatment of paroxysmal movement disorders

ABSTRACT Introduction Paroxysmal movement disorders mostly comprise paroxysmal dyskinesia and episodic ataxia, and can be the consequence of a genetic disorder or symptomatic of an acquired disease. Areas covered In this review, the authors focused on certain hot-topic issues in the field: the respective contribution of the cerebellum and striatum to the generation of paroxysmal dyskinesia, the importance of striatal cAMP turnover in the pathogenesis of paroxysmal dyskinesia, the treatable causes of paroxysmal movement disorders not to be missed, with a special emphasis on the treatment strategy to bypass the glucose transport defect in paroxysmal movement disorders due to GLUT1 deficiency, and functional paroxysmal movement disorders. Expert opinion Treatment of genetic causes of paroxysmal movement disorders is evolving towards precision medicine with targeted gene-specific therapy. Alteration of the cerebellar output and modulation of the striatal cAMP turnover offer new perspectives for experimental therapeutics, at least for paroxysmal movement disorders due to selected causes. Further characterization of cell-specific molecular pathways or network dysfunctions that are critically involved in the pathogenesis of paroxysmal movement disorders will likely result in the identification of new biomarkers and testing of innovative-targeted therapeutics.
LonGP: an additive Gaussian process regression model for longitudinal study designs

Motivation Biomedical research typically involves longitudinal study designs where samples from individuals are measured repeatedly over time and the goal is to identify risk factors (covariates) that are associated with an outcome value. General linear mixed effect models have become the standard workhorse for statistical analysis of data from longitudinal study designs. However, analysis of longitudinal data can be complicated for both practical and theoretical reasons, including difficulties in modelling, correlated outcome values, functional (time-varying) covariates, nonlinear effects, and model inference. Results We present LonGP, an additive Gaussian process regression model for analysis of experimental data from longitudinal study designs. LonGP implements a flexible, non-parametric modelling framework that solves commonly faced challenges in longitudinal data analysis. In addition to inheriting all standard features of Gaussian processes, LonGP can model time-varying random effects and non-stationary signals, incorporate multiple kernel learning, and provide interpretable results for the effects of individual covariates and their interactions. We develop an accurate Bayesian inference and model selection method, and implement an efficient model search algorithm for our additive Gaussian process model. We demonstrate LonGP’s performance and accuracy by analysing various simulated and real longitudinal -omics datasets. Our work is accompanied by a versatile software implementation. Availability LonGP software tool is available at http://research.cs. aalto.fi/csb/software/longp/. Contact lu.cheng. ac@gmail.com, harri.lahdesmaki@aalto.fi
3D printed micro-chambers carrying stem cell spheroids and pro-proliferative growth factors for bone tissue regeneration

Three-dimensional (3D)-printed scaffolds have proved to be effective tools for delivering growth factors and cells in bone-tissue engineering. However, delivering spheroids that enhance cellular function remains challenging because the spheroids tend to suffer from low viability, which limits bone regeneration in vivo. Here, we describe a 3D-printed polycaprolactone micro-chamber that can deliver human adipose-derived stem cell spheroids. An in vitro culture of cells from spheroids in the micro-chamber exhibited greater viability and proliferation compared with cells cultured without the chamber. We coated the surface of the chamber with 500 ng of platelet-derived growth factors (PDGFs), and immobilized 50 ng of bone morphogenetic protein 2 (BMP-2) on fragmented fibers, which were incorporated within the spheroids as a new platform for a dual-growth-factor delivery system. The PDGF detached from the chamber within 8 h and the remains were retained on the surface of chamber while the BMP-2 was entrapped by the spheroid. In vitro osteogenic differentiation of the cells from the spheroids in the micro-chamber with dual growth factors enhanced alkaline phosphatase and collagen type 1A expression by factors of 126.7 ± 19.6 and 89.7 ± 0.3, respectively, compared with expression in a micro-chamber with no growth factors. In vivo transplantation of the chambers with dual growth factors into mouse calvarial defects resulted in a 77.0 ± 15.9% of regenerated bone area, while the chamber without growth factors and a defect-only group achieved 7.6 ± 3.9% and 5.0 ± 1.9% of regenerated bone areas, respectively. These findings indicate that a spheroid-loaded micro-chamber supplied with dual growth factors can serve as an effective protein-delivery platform that increases stem-cell functioning and bone regeneration.
Acute effects of caloric intake and macronutrient type on body weight, body composition, resting energy expenditure, and total metabolic rate.

Acute Effects of Caloric Intake and Macronutrient Type on Body Weight, Body Composition, Resting Energy Expenditure, and Total Metabolic Rate Ashli Thomas, B.S., R.D. , L.D. Committee Chairperson: Richard B. Kreider, Ph.D. Obesity is a growing epidemic with no consensus regarding solutions. Thirty healthy overweight and obese female subjects (41.9 ± 12 years, 166 cm ± 7 cm, a 100.5 kg ± 19.6 kg, 46.0% ± 4.0% body fat, and BMI 37.4 ± 6.9) participated in the study. A 14-day dietary intervention examined acute effects of energy balance and macronutrient type on dietary intake, REE, body weight, body composition, and thyroid panel. Significant changes occurred in weight loss over time (p < 0.001); body fat mass over time (p < 0.001) and time x diet (p = 0.02); body fat percentage over time (p < 0.002) and time x diet (p = 0.023); REE over time (p = 0.03), and thyroid panel. Body weight continued to decrease during positive energy balance, yet metabolism rebounded. Results suggest energy balance has a greater overall effect on REE and weight loss than macronutrient type.