Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of intra-islet heparan sulfate is a highly sensitive marker of type 1 diabetes progression in humans

Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta cells in pancreatic islets are progressively destroyed. Clinical trials of immunotherapies in recently diagnosed T1D patients have only transiently and partially impacted the disease course, suggesting that other approaches are required. Our previous studies have demonstrated that heparan sulfate (HS), a glycosaminoglycan conventionally expressed in extracellular matrix, is present at high levels inside normal mouse beta cells. Intracellular HS was shown to be critical for beta cell survival and protection from oxidative damage. T1D development in Non-Obese Diabetic (NOD) mice correlated with loss of islet HS and was prevented by inhibiting HS degradation by the endoglycosidase, heparanase. In this study we investigated the distribution of HS and heparan sulfate proteoglycan (HSPG) core proteins in normal human islets, a role for HS in human beta cell viability and the clinical relevance of intra-islet HS and HSPG levels, compared to insulin, in human T1D. In normal human islets, HS (identified by 10E4 mAb) co-localized with insulin but not glucagon and correlated with the HSPG core proteins for collagen type XVIII (Col18) and syndecan-1 (Sdc1). Insulin-positive islets of T1D pancreases showed significant loss of HS, Col18 and Sdc1 and heparanase was strongly expressed by islet-infiltrating leukocytes. Human beta cells cultured with HS mimetics showed significantly improved survival and protection against hydrogen peroxide-induced death, suggesting that loss of HS could contribute to beta cell death in T1D. We conclude that HS depletion in beta cells, possibly due to heparanase produced by insulitis leukocytes, may function as an important mechanism in the pathogenesis of human T1D. Our findings raise the possibility that intervention therapy with dual activity HS replacers/heparanase inhibitors could help to protect the residual beta cell mass in patients recently diagnosed with T1D.
Effect of Inhaled Nebulized Furosemide (40 and 120 mg) on Breathlessness during Exercise in the Presence of External Thoracic Restriction in Healthy Men

Inhalation of nebulized furosemide has been shown to alleviate breathlessness provoked experimentally in health and disease; however, it remains unclear whether the efficacy of nebulized furosemide on breathlessness is dose-dependent. We tested the hypothesis that inhaled nebulized furosemide would be associated with a dose-dependent relief of breathlessness during exercise testing in the setting of abnormal restrictive constraints on tidal volume (VT) expansion. In a randomized, double-blind, crossover study, 24 healthy men aged 25.3 ± 1.2 years (mean ± SE) completed a symptom-limited constant-load cycle endurance exercise test in the setting of external thoracic restriction via chest wall strapping to reduce vital capacity by ~20% following single-dose inhalation nebulized furosemide (40 and 120 mg) and 0.9% saline. Compared with 0.9% saline, neither 40 nor 120 mg of inhaled nebulized furosemide had an effect on ratings of perceived breathlessness during exercise or an effect on cardiometabolic, ventilatory, breathing pattern, or dynamic operating lung volume responses during exercise. Urine production rate, the percentage of participants reporting an “urge to urinate” and the intensity of perceived “urge to urinate” were all significantly greater after inhaling the 120 mg furosemide solution compared with both 0.9% saline and 40 mg furosemide solutions. We concluded that, under the experimental conditions of this study, inhalation of nebulized furosemide at doses of 40 and 120 mg did not alleviate breathlessness during exercise in healthy men.
Age-Dependent Modulations of Resting State Connectivity Following Motor Practice

Recent work in young adults has demonstrated that motor learning can modulate resting state functional connectivity. However, evidence for older adults is scarce. Here, we investigated whether learning a bimanual tracking task modulates resting state functional connectivity of both inter- and intra-hemispheric regions differentially in young and older individuals, and whether this has behavioral relevance. Both age groups learned a set of complex bimanual tracking task variants over a 2-week training period. Resting-state and task-related functional magnetic resonance imaging scans were collected before and after training. Our analyses revealed that both young and older adults reached considerable performance gains. Older adults even obtained larger training-induced improvements relative to baseline, but their overall performance levels were lower than in young adults. Short-term practice resulted in a modulation of resting state functional connectivity, leading to connectivity increases in young adults, but connectivity decreases in older adults. This pattern of age differences occurred for both inter- and intra-hemispheric connections related to the motor network. Additionally, long-term training-induced increases were observed in intra-hemispheric connectivity in the right hemisphere across both age groups. Overall, at the individual level, the long-term changes in inter-hemispheric connectivity correlated with training-induced motor improvement. Our findings confirm that short-term task practice shapes spontaneous brain activity differentially in young and older individuals. Importantly, the association between changes in resting state functional connectivity and improvements in motor performance at the individual level may be indicative of how training shapes the short-term functional reorganization of the resting state motor network for improvement of behavioral performance.
Prognostic role of NF-YA splicing isoforms and Lamin A status in low grade endometrial cancer

Although most cases of low grade (G1) endometrial cancer (EC) do not behave aggressively, in rare instances, can progress in a highly aggressive manner. In this study we analyzed formalin-fixed, paraffin-embedded (FFPE) EC tissues to find novel clinical and biological features to help diagnosis and treatment of G1 ECs s in order to better stratify patient risk of recurrence. A retrospective cohort of FFPE specimens from patients with EC (n=87) and benign tissue specimens (NE) from patients who underwent a hysterectomy to treat other benign disease (n = 13) were collected. Total RNA and proteins were extracted and analyzed, respectively, by quantitative PCR and western blotting. NF-YAs is expressed and lamin A is down-modulated in all high grade (G2 and G3) ECs. In G1 ECs, NF-YAs expression is heterogeneous being expressed only in a subset of these tumours. Interestingly, the G1 ECs that express NF-YAs display low levels of lamin A similar to those present in G2 and G3 ECs. Of note, this pattern of NF-YAs and lamin A expression correlates with tumor aggressiveness assessed by comparative analysis with estrogen receptor (ER) status and epithelial-mesenchymal transition (EMT) markers thus suggesting its potential role as biomarker of tumour aggressiveness in G1 EC. In all grade ECs, lamin A is strongly downmodulated, being its expression inversely correlated with tumor aggressiveness and its loss of expression. We identified NF-YAs and lamin A expression levels as novel potential biomarkers useful to identify G1 ECs patients with risk of recurrence.
Stereotype Threat as a Trigger of Mind-Wandering in Older Adults

Older adults (OAs) report less overall mind-wandering than younger adults (YAs) but more task-related interference (TRI; mind-wandering about the task). The current study examined TRI while manipulating older adults’ performance-related concerns. We compared groups for which memory-related stereotype threat (ST) was activated or relieved to a control group. Participants completed an operation span task containing mind-wandering probes. ST-activated OAs reported more TRI than ST-relieved OAs and had worse performance on the operation span task. This study illustrates that environmental context triggers current concerns and determines, in part, the frequency and content of mind-wandering.
Deep Multi-View Spatial-Temporal Network for Taxi Demand Prediction

Taxi demand prediction is an important building block to enabling intelligent transportation systems in a smart city. An accurate prediction model can help the city pre-allocate resources to meet travel demand and to reduce empty taxis on streets which waste energy and worsen the traffic congestion. With the increasing popularity of taxi requesting services such as Uber and Didi Chuxing (in China), we are able to collect large-scale taxi demand data continuously. How to utilize such big data to improve the demand prediction is an interesting and critical real-world problem. Traditional demand prediction methods mostly rely on time series forecasting techniques, which fail to model the complex non-linear spatial and temporal relations. Recent advances in deep learning have shown superior performance on traditionally challenging tasks such as image classification by learning the complex features and correlations from large-scale data. This breakthrough has inspired researchers to explore deep learning techniques on traffic prediction problems. However, existing methods on traffic prediction have only considered spatial relation (e.g., using CNN) or temporal relation (e.g., using LSTM) independently. We propose a Deep Multi-View Spatial-Temporal Network (DMVST-Net) framework to model both spatial and temporal relations. Specifically, our proposed model consists of three views: temporal view (modeling correlations between future demand values with near time points via LSTM), spatial view (modeling local spatial correlation via local CNN), and semantic view (modeling correlations among regions sharing similar temporal patterns). Experiments on large-scale real taxi demand data demonstrate effectiveness of our approach over state-of-the-art methods.
High Prevalence of Gestational Diabetes Mellitus in Beijing: Effect of Maternal Birth Weight and Other Risk Factors

Background: Gestational diabetes mellitus (GDM) is associated with both short- and long-term adverse health consequences for both the mother and her offspring. The aim was to study the prevalence and risk factors for GDM in Beijing. Methods: The study population consisted of 15,194 pregnant women attending prenatal care in 15 hospitals in Beijing, who delivered between June 20, 2013, and November 30, 2013, after 28 weeks of gestation. The participants were selected by cluster sampling from the 15 hospitals identified through random systematic sampling based on the number of deliveries in 2012. A questionnaire was designed to collect information. Results: A total of 2987 (19.7%) women were diagnosed with GDM and 208 (1.4%) had diabetes in pregnancy (DIP). Age (OR: 1.053, 95% CI: 1.033–1.074, P < 0.01), family history of diabetes mellitus (OR: 1.481, 95% CI: 1.254–1.748, P < 0.01), prepregnancy body mass index (BMI) (OR: 1.481, 95% CI: 1.254–1.748, P < 0.01), BMI gain before 24 weeks (OR: 1.126, 95% CI: 1.075–1.800, P < 0.01), maternal birth weight (P < 0.01), and fasting plasma glucose at the first prenatal visit (P < 0.01) were identified as risk factors for GDM. In women with birth weight <3000 g, GDM rate was significantly higher. Conclusions: One out of every five pregnant women in Beijing either had GDM or DIP and this constitutes a huge health burden for health services. Prepregnancy BMI and weight gain before 24th week are important modifiable risk factors for GDM. Ensuring birth weight above 3000 g may help reduce risk for future GDM among female offsprings.
Parameter calculation of round rotor synchronous generators using phasor measurements signals

A combinational method for calculation of dynamic parameters of a round rotor synchronous generator in an 80 MVA, 10.5 KV power plant based on synchronous reactance calculation from phasor measurements and using rated value of control room signals is developed in this paper. The results of this analytical method, in comparison with other methods show the efficiency and accuracy of the proposed method.
Three‐dimensional mapping of the arteriovenous loop model using two‐dimensional histological methods

The aim of this study was to create an analytical tool for the three‐dimensional distribution of immunohistochemically stained cells in the arteriovenous (AV) loop model of the femoral vessels of rats that fuses two‐dimensional histological slides into stacks. Methods: A total of 22 AV loops were implanted into male syngeneic Lewis rats by creating an arteriovenous fistula between the femoral artery and vein by interposing a femoral vein graft of the contralateral extremity. This fistula was embedded into an isolation chamber filled with a fibrin matrix. Specimens were explanted after 7 to 14 days, and the AV loop was processed using standard histological protocols. Immunohistochemical staining for HIF‐1α and a counter staining with hematoxylin was performed. Various layouts with different cutting planes, regions of interest, and post‐processing algorithms were evaluated. Results and observations: The proximal‐to‐distal cutting perpendicular to the vascular axis proved to be the best layout for mapping the three‐dimensional constructs containing the AV loop. A semi‐automatic algorithm for the differentiation of immunohistochemical positive and negative cells was developed. Conclusion: The newly established methods from this study constitute an excellent tool for the general evaluation of the AV loop model – particularly with regard to the three‐dimensional distribution of immunohistochemical positive and negative cells.
Participatory Design in Emerging Civic Engagement Initiatives in the New Public Sector

In this study, we address the role of Participatory Design (PD) in emerging public sector governance forms and, more specifically, civic engagement and we-government initiatives. We achieve this by first providing a research overview of the development of PD approaches since they originated in the 1970s, identifying different PD generations and associated concepts, contexts, and challenges, and then relating them to current public sector trends. Next, we link the overview to a practical example by presenting a case of applying PD to a civic engagement project that takes place in the Swedish emergency response system. Our example findings sustain previously identified needs to return to broad change processes and balance this with ICT re-configuration and structuration of the collaborative processes, the related stakeholders, and their needs, this time in a context where work tasks and responsibilities are not yet defined, known or experienced among stakeholders. We then suggest methodological ways to handle this by (1) applying an interdisciplinary PD approach, (2) replacing the traditional design group with a combination of various qualitative methods and PD techniques, e.g., focus groups, modified scenario-based future workshops, exercises, and after-action-reviews, and (3) support PD activities with context-specific frameworks. We argue that applying PD concepts to the governance forms that are emerging in resource-constrained public sector organizations poses a number of challenges, many of them relating directly to the unknown character of the work setting and the practical difficulties of involving civil citizens as end-users. However, if they are addressed and handled adequately, making civic engagement initiatives work processes and ICT support to work smoothly, this can contribute to a re-politicization of PD in terms of space, action, and the empowerment of citizens both by enhancing their skills and by having them represented in design activities.
Data logger technologies for manual wheelchairs: A scoping review

ABSTRACT In recent years, studies have increasingly employed data logger technologies to record objective driving and physiological characteristics of manual wheelchair users. However, the technologies used offer significant differences in characteristics, such as measured outcomes, ease of use, and level of burden. In order to identify and describe the extent of published research activity that relies on data logger technologies for manual wheelchair users, we performed a scoping review of the scientific and gray literature. Five databases were searched: Medline, Compendex, CINAHL, EMBASE, and Google Scholar. The 119 retained papers document a wide variety of logging devices and sensing technologies measuring a range of outcomes. The most commonly used technologies were accelerometers installed on the user (18.8%), odometers installed on the wheelchair (12.4%), accelerometers installed on the wheelchair (9.7%), and heart monitors (9.7%). Not surprisingly, the most reported outcomes were distance, mobility events, heart rate, speed/velocity, acceleration, and driving time. With decreasing costs and technological improvements, data loggers are likely to have future widespread clinical (and even personal) use. Future research may be needed to assess the usefulness of different outcomes and to develop methods more appropriate to wheelchair users in order to optimize the practicality of wheelchair data loggers.
Discovery of Covalent Ligands via Noncovalent Docking by Dissecting Covalent Docking Based on a "Steric-Clashes Alleviating Receptor (SCAR)" Strategy

Covalent ligands modulating protein activities/signals have attracted unprecedented attention in recent years, but the insufficient understanding of their advantages in the early days of drug discovery has hindered their rational discovery and development. This also left us inadequate knowledge on the rational design of covalent ligands, e.g., how to balance the contribution from the covalent group and the noncovalent group, respectively. In this work, we dissected the noncovalent docking from covalent docking by creating SCARs (steric-clashes alleviating receptors). We showed that the SCAR method outperformed those specifically developed but more complicated covalent docking protocols. We furthermore provided a "proof-of-principle" example by implementing this method in the first high-throughput screening and discovery of novel covalent inhibitors of S-adenosylmethionine decarboxylase. This work demonstrated that noncovalent groups play a predeterminate role in the design of covalent ligands, and would be of great value in accelerating the discovery and development of covalent ligands.
SAPF with two Dc-links and series converters feeding OEW transformers for 3P4W systems

This paper presents a shunt active power filter (SAPF) topology, based on the concept of a transformer with open-end winding (OEW), for reactive power and harmonic compensations employed in three-phase four wire (3P4W) systems under balanced and unbalanced conditions. The proposed system uses two independent dc-links and two independent converters series connected through transformers. Complete system control, including PWM technique, is developed and a comparison between the proposed SAPF and conventional one is presented as well. Simulation and experimental results are provided to validate the theoretical approach.
Cost-effectiveness analysis of different seasonal influenza vaccines in the elderly Italian population

ABSRACT In the perspective of reaching at least 75% influenza vaccination coverage in the elderly and substantial budget constraints, Italian decision makers are facing important challenges in determining an optimal immunization strategy for this growing and particularly vulnerable population. Four different influenza vaccines are currently available for Italian older adults aged 65 years or above, namely trivalent inactivated vaccines (TIVs), MF59-adjuvanted TIV (MF59-TIV), intradermal TIV (ID-TIV) and quadrivalent inactivated vaccines (QIVs). The present study is the first to compare the cost-effectiveness profiles of virtually all possible public health strategies, including the aforementioned four vaccine formulations as well non-vaccination. For this purpose, a decision tree model was built ex novo; the analysis was conducted from the third-payer perspective in the timeframe of one year. All available vaccines were cost-effective compared with non-vaccination. However, MF59-TIV had the most favorable economic profile in the Italian elderly population. Indeed, compared with non-vaccination, it was deemed highly cost-effective with an incremental cost-effectiveness ratio (ICER) of €10,750 per quality-adjusted life year (QALY). The ICER was much lower (€4,527/QALY) when MF59-TIV was directly compared with TIV. ID-TIV and QIV were dominated by MF59-TIV as the former comparators were associated with greater total costs and lower health benefits. Both deterministic and probabilistic sensitivity analyses confirmed robustness of the base case results. From the economic perspective, MF59-TIV should be considered as a preferential choice for Italian older adults aged 65 years or above.
Protective effects of PPAR‐γ against pregnancy‐induced hypertension by differential ETR expression in rat models

This study aims to investigate the effects of PPAR‐γ on rats with pregnancy‐induced hypertension (PIH) by regulating endothelin receptor (ETR). A total of 60 pregnant Wistar rats were selected, and 50 rats were used to establish endotoxin induced PIH rat models. Rats were equally assigned into PIH‐NS, PIH‐5 mg/kg RM, PIH‐10 mg/kg RM, PIH‐100 mg/kg ETR, and PIH‐200 mg/kg ETR groups, and the rest 10 rats were assigned to a the control group. Reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and Western blotting were used for determining mRNA and protein expressions of PPAR‐γ and ETAR, respectively. Protein expression of ET‐1 was detected by immunohistochemistry. Results show that On the 22nd day of pregnancy, compared with the PIH‐NS group, SBP decreased in other groups, and platelet concentration increased most significantly in the PIH‐10 mg/kg RM and PIH‐200 mg/kg ETR groups. Compared with the control, PIH‐10 mg/kg RM and PIH‐200 mg/kg ETR groups, the increase in the expression of ET‐1 and ETAR was most significant in the PIH‐NS group. Compared with the control and PIH‐10 mg/kg RM groups, expression of PPAR‐γ was lower in the PIH‐NS, PIH‐5 mg/kg RM, PIH‐100 mg/kg ETR, and PIH‐200 mg/kg ETR groups. Compared with the PIH‐NS, PIH‐100 mg/kg ETR and PIH‐200 mg/kg ETR groups, PPAR‐γ expression was significantly higher in the PIH‐5 mg/kg RM group (all P < 0.05). Based on our findings, we conclude that PPAR‐γ activation inhibits ETR expression and reduces the effect of ET‐1 on vascular contraction thereby delaying PIH progression.
Flexural properties of composite gypsum partition panel

Bending tests were conducted on prismatic samples of gypsum panels with a core of textile waste fibres. The samples were prepared by confining the waste textile fibres with glass fibre mesh (GFM). The dimensions of the fibre core and the type of mesh employed were used as variables to obtain optimal flexural strength and energy absorption capability. The test results revealed that the gypsum panels with a central core of textile waste fibres have high ductility and high energy absorption capacity. It was concluded that using textile waste materials and GFMs embedded in gypsum can produce three-layer partitions and reduce the landfilling of textile wastes.