Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelium‐dependent responses in the microcirculation observed in vivo

Endothelium‐dependent responses were first demonstrated 40 years ago in the aorta. Since then, extensive research has been conducted in vitro using conductance vessels and materials derived from them. However, the microcirculation controls blood flow to vital organs and has been the focus of in vivo studies of endothelium‐dependent dilation beginning immediately after the first in vitro report. Initial in vivo studies employed a light/dye technique for selectively damaging the endothelium to unequivocally prove, in vivo, the existence of endothelium‐dependent dilation and in the microvasculature. Endothelium‐dependent constriction was similarly proven. Endothelium‐dependent agonists include acetylcholine (ACh), bradykinin, arachidonic acid, calcium ionophore A‐23187, calcitonin gene‐related peptide (CGRP), serotonin, histamine and endothelin‐1. Normal and disease states have been studied. Endothelial nitric oxide synthase, cyclooxygenase and cytochrome P450 have been shown to generate the mediators of the responses. Some of the key enzyme systems generate reactive oxygen species (ROS) like superoxide which may prevent EDR. However, one ROS, namely H2O2, is one of a number of hyperpolarizing factors that cause dilation initiated by endothelium. Depending upon microvascular bed, a single agonist may use different pathways to elicit an endothelium‐dependent response. Interpretation of studies using inhibitors of eNOS is complicated by the fact that these inhibitors may also inhibit ATP‐sensitive potassium channels. Other in vivo observations of brain arterioles failed to establish nitric oxide as the mediator of responses elicited by CGRP or by ACh and suggest that a nitrosothiol may be a better fit for the latter.
Self‐Stabilized Hyaluronate Nanogel for Intracellular Codelivery of Doxorubicin and Cisplatin to Osteosarcoma

Osteosarcoma is one of the most serious bone malignancies with rapid speed of deterioration and low survival rate in children and teenagers. Chemotherapy is an important treatment for osteosarcoma, while the conventional small‐molecule therapeutics exhibit low efficacies and severe side effects in the clinic. Drug‐delivery platforms based on nanotechnology, particularly for self‐stabilized delivery platforms with prolonged blood circulation, enhanced intratumoral accumulation, improved antitumor efficacy, and diminished side effects, may break the deadlock on osteosarcoma chemotherapy. Here, a cisplatin (CDDP)‐crosslinked hyaluronic acid (HA) nanogel (CDDPHANG) is prepared for effective delivery of doxorubicin (DOX) to treat osteosarcoma. Importantly, both DOX and CDDP have led clinically used antitumor drugs, and CDDP acts as a crosslinker and ancillary anticarcinogen to prevent the premature release of DOX and to achieve synergistic therapeutic performance. Because of the enhanced stability of the nanogel, this CDDP‐crosslinked DOX‐loaded nanomedicine (CDDPHANG/DOX) exhibits an obviously prolonged circulation time compared to free drugs. Moreover, after valid tumor accumulation, DOX and CDDP are synergistically delivered into the tumor cells and synchronously released into the intracellular acidic environment. Based on the synergistic apoptosis‐inducing effects of DOX and CDDP, CDDPHANG/DOX reveals an evidently enhanced antitumor efficacy compared to free drugs and their combination, indicating its great prospects for the chemotherapy of osteosarcoma.
CEP Discussion Paper No 1543 April 2018 Firm-to-Firm Connections in Colombian Imports

The vast majority of world trade flows is between firms. Only recently has research in international trade started to emphasize the importance of the connections between exporters and importers both in aggregate trade flows and in the negative relationship between trade and geographic distance. This chapter documents the role of firm-to-firm connections in trade flows and the formation and duration of these importer-exporter relationships. Using customs data from Colombia for 1995-2014, we are able to identify both the Colombian importing firm and the foreign exporter in every Colombian import and export transaction. We document both the nature of these bilateral trading relationships and their evolution over time.
Love and Hate Relationships in a Platform Ecosystem: A case of Finnish Electronic Identity Management

There has been a substantial interest among scholars in digital platforms and their governance. This paper proposes a different perspective on the phenomenon, by providing observations on non-focal firms’ dependencies to external platforms. Using the case study results of Finnish firms’ utilization of a monopolistic BankID authentication platform, we describe the platform ecosystem and its transformation on organizational and technology aspects. We show how legislation can transform the roles and relations between ecosystem participants and lead to the long-time dominant legacy platform weakening. Our study extends existing research on platforms and contributes new knowledge about the enforced adoption of the platform by heterogeneous organizations. These findings have important managerial implications, as they inform how non-focal firms can understand the use of existing and coming digital platforms.
Press Freedom Homophily in the Tie Structure of the Global Internet

We investigate homophily in the tie structure of the global Internet by estimating Exponential Random Graph models. Specifically, we analyze the extent to which different variables including Gross National Income, geographic proximity, political regime type, and press freedom rating account for the pattern of direct country-to-country Internet connections. Results show that for 2011-2014, but not before, press freedom homophily is significantly predictive of the presence (or absence) of country-to-country Internet connections even when controlling for geographic proximity, bandwidth, and whether or not a country is democratic. The findings provide insights into changes in press freedom around the world and the evolution of the global Internet structure.
The Correlation between Daily Lens Wear Duration and Dry Eye Syndrome

AIM: To analyze the correlation between the daily lens wear duration and dry eye syndrome. SUBJECTS AND METHODS: This study was an analytic cross sectional study using consecutive sampling conducted among the students in Economy and Bussiness Faculty and Faculty of Humanities in University of Sumatera Utara aged between 17 to 23 that wore contact lens continously for at least a year and 5 days a week. The symptoms were assessed using Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and interview about their contact lens comfort; eye drops usage, contact lens washing habit, daily circumstances, places to buy contact lens and personal experince in wearing contact lens. RESULTS: The questionnaire was completed by 53 students. All of them were female and wore softlens wearers. The mean duration of daily wear was 8.19 ± 2.20 hours. The most common symptom experienced was dry eye and the least symptom experienced was removing lens. The most frequent symptom experienced was closing eyes and the least frequent symptom experienced was removing lenses. This study used Exact Test as analysis statistic method. The result was p > 0.05 which means there is no correlation between daily lens wear duration and dry eye syndrome. CONCLUSION: This study showed that dry eye syndrome was not correlated with daily lens wear duration, but affected by many factors such as contact lens, lens care solution, eye drops usage and environment.
Small RNA profiling in Mycobacterium tuberculosis identifies MrsI as necessary for an anticipatory iron sparing response

Significance This work describes the most extensive discovery and functional characterization of small regulatory RNAs (sRNAs) in Mycobacterium tuberculosis to date. We comprehensively define the sRNAs expressed in M. tuberculosis under five host-like stress conditions. This reference dataset comprehensively defines the expression patterns and boundaries of mycobacterial sRNAs. We perform in-depth characterization of one sRNA, mycobacterial regulatory sRNA in iron (MrsI), which is induced in M. tuberculosis in multiple stress conditions. MrsI is critical for the iron-sparing response in mycobacteria by binding directly to mRNAs encoding nonessential iron-containing proteins to repress their expression. Interestingly, MrsI acts in an anticipatory manner, in which its induction by a variety of stresses primes M. tuberculosis to enter an iron-sparing state more rapidly upon iron deprivation. One key to the success of Mycobacterium tuberculosis as a pathogen is its ability to reside in the hostile environment of the human macrophage. Bacteria adapt to stress through a variety of mechanisms, including the use of small regulatory RNAs (sRNAs), which posttranscriptionally regulate bacterial gene expression. However, very little is currently known about mycobacterial sRNA-mediated riboregulation. To date, mycobacterial sRNA discovery has been performed primarily in log-phase growth, and no direct interaction between any mycobacterial sRNA and its targets has been validated. Here, we performed large-scale sRNA discovery and expression profiling in M. tuberculosis during exposure to five pathogenically relevant stresses. From these data, we identified a subset of sRNAs that are highly induced in multiple stress conditions. We focused on one of these sRNAs, ncRv11846, here renamed mycobacterial regulatory sRNA in iron (MrsI). We characterized the regulon of MrsI and showed in mycobacteria that it regulates one of its targets, bfrA, through a direct binding interaction. MrsI mediates an iron-sparing response that is required for optimal survival of M. tuberculosis under iron-limiting conditions. However, MrsI is induced by multiple host-like stressors, which appear to trigger MrsI as part of an anticipatory response to impending iron deprivation in the macrophage environment.
An “Exercise” in Cardiac Metabolism

Research has demonstrated that the high capacity requirements of the heart are satisfied by a preference for oxidation of fatty acids. However, it is well known that a stressed heart, as in pathological hypertrophy, deviates from its inherent profile and relies heavily on glucose metabolism, primarily achieved by an acceleration in glycolysis. Moreover, it has been suggested that the chronically lipid overloaded heart augments fatty acid oxidation and triglyceride synthesis to an even greater degree and, thus, develops a lipotoxic phenotype. In comparison, classic studies in exercise physiology have provided a basis for the acute metabolic changes that occur during physical activity. During an acute bout of exercise, whole body glucose metabolism increases proportionately to intensity while fatty acid metabolism gradually increases throughout the duration of activity, particularly during moderate intensity. However, the studies in chronic exercise training are primarily limited to metabolic adaptations in skeletal muscle or to the mechanisms that govern physiological signaling pathways in the heart. Therefore, the purpose of this review is to discuss the precise changes that chronic exercise training elicits on cardiac metabolism, particularly on substrate utilization. Although conflicting data exists, a pattern of enhanced fatty oxidation and normalization of glycolysis emerges, which may be a therapeutic strategy to prevent or regress the metabolic phenotype of the hypertrophied heart. This review also expands on the metabolic adaptations that chronic exercise training elicits in amino acid and ketone body metabolism, which have become of increased interest recently. Lastly, challenges with exercise training studies, which could relate to several variables including model, training modality, and metabolic parameter assessed, are examined.
Detection of early osteoarthritis in canine knee joints 3 weeks post ACL transection by microscopic MRI and biomechanical measurement

Purpose: To detect early osteoarthritis (OA) in a canine Pond–Nuki model 3 weeks after anterior cruciate ligament (ACL) transection surgery, both topographically over the medial tibial surface and depth-dependently over the cartilage thickness. Methods: Four topographical locations on each OA and contralateral medial tibia were imaged individually by magnetic resonance imaging (MRI) at 17.6 µm transverse resolution. The quantitative MRI T2 relaxation data were correlated with the biomechanical stress-relaxation measurements from adjacent locations. Results: OA cartilage was thinner than the contralateral tissue and had a lower modulus compared to the contralateral cartilage for the exterior, interior, and central medial tibia locations. Depth-dependent and topographical variations were detected in OA cartilage by a number of parameters (compressive modulus, glycosaminoglycan concentration, bulk and zonal thicknesses, T2 at 0° and 55° specimen orientations in the magnet). T2 demonstrated significant differences at varying depths between OA and contralateral cartilage. Conclusion: ACL transection caused a number of changes in the tibial cartilage at 3 weeks after the surgery. The characteristics of these changes, which are topographic and depth-dependent, likely reflect the complex degradation in this canine model of OA at the early developmental stage.
Lean body mass wasting and toxicity in early breast cancer patients receiving anthracyclines

Background Sarcopenia refers to the reduction of both volume and number of skeletal muscle fibers. Lean body mass loss is associated with survival, quality of life and tolerance to treatment in cancer patients. The aim of our study is to analyse the association between toxicities and sarcopenia in early breast cancer patients receiving adjuvant treatment. Materials and Methods Breast cancer patients who have received anthracycline-based adjuvant treatment were retrospectively enrolled. CT scan images performed before, during and after adjuvant chemotherapy were used to evaluate lean body mass at third lumbar vertebra level with the software Slice Omatic V 5.0. Results 21 stage I–III breast cancer patients were enrolled. According to the skeletal muscle index at third lumbar vertebra cut-off ≤38.5 cm2/m2, 8 patients (38.1%) were classified as sarcopenic before starting treatment, while 10 patients (47.6%) were sarcopenic at the end of treatment. A lower baseline L3 skeletal muscle index is associated with G3-4 vs G0-2 toxicities (33.4 cm2/m2 (31.1–39.9) vs 40.5 cm2/m2 (33.4–52.0), p = 0.028). Similarly skeletal muscle cross sectional area was significantly lower in patients with G3-4 toxicities (86.7 cm2 (82.6–104.7) vs 109.0 cm2 (83.3–143.9), p = 0.017). L3 skeletal muscle index is an independent predictor of severe toxicity (p = 0.0282) in multivariate analysis. Conclusion Lean body mass loss is associated with higher grade of toxicity in early breast cancer patients receiving adjuvant chemotherapy.
Trust and Distrust in Two-sided Markets: An Example in the Sharing Economy

Mobile applications and Internet-based platforms continuously foster the rise of the sharing economy business model that can nowadays be found in various industries. In this paper, we focus on potential customers in the ridesharing industry. We use the setting of ‘BlaBlaCar’, a popular ridesharing platform, to investigate the implications of ‘trust’ and ‘distrust’ on the users’ intention to engage in a sharing encounter. In particular, we extend the research model by Mittendorf (2017) which investigates the influence of trust and risk in the sharing economy. In this regard, we differentiate between the platform and the sharing partners, while incorporating both trust and distrust. Our study employs survey data (n = 238) and structural equation modeling (PLS-SEM). Our results provide empirical evidence that trust and distrust have unequal effects on the respective user intention, which contributes to the understanding of two-sided market platforms. Academic and practical implications are discussed.
Self-affirmation enhances processing of negative stimuli among threat-prone individuals

Abstract Self-affirmation reduces defensive responding to self-threats. The present study extended beyond self-threats to assess affirmation’s influence on responses to negative emotional pictures as measured by the late positive potential (LPP), an event-related potential in the encephalogram that reflects motivational significance. Participants completed a trait measure of behavioral inhibition system (BIS) sensitivity. Then they affirmed (or did not affirm) a core personal value before viewing a series of emotionally evocative pictures. Affirming a core value increased LPP responses to negative emotional pictures among individuals higher in BIS. Self-affirmation thus appeared to alter the motivational significance of negative pictures among threat-prone individuals, consistent with a reduction in the defensive avoidance of aversive stimuli. These findings suggest that affirming values may influence responses associated with basic (non-self) motivational systems among individuals sensitive to threat.
β-Cyclodextrin Covalent Organic Framework for Selective Molecular Adsorption.

Covalent organic frameworks (COF) are complex functional systems constructed with atomic precision by linking well-defined building blocks through robust covalent bonds. β-cyclodextrin (β-CD) is a most employed supramolecule which bears a hydrophobic cavity guiding molecular specific recognitions. Building COF with asymmetric β-CD linkers is challenging and has never been reported. Here, β-CD COF is grown with heptakis(6-amino-6-deoxy)-β-CD and terephthalaldehyde in green solvents of water and ethanol at room temperature. The COF is characterized by powder X-ray diffraction, which matches well with the simulated crystal structure. Weaving β-CD into a framework through reticular chemistry allows the integration of a large amount of β-CD units (50 mol %), much higher than β-CD polymers. The β-CD COF has larger surface area, more uniform pore size, and higher thermal stability than the non-crystalline β-CD polymer produced by the same reagents. Finally, the β-CD COF holds abundant specific interaction sites enabling selective molecular adsorption.
Extracting Actionable Knowledge from Domestic Violence Discourses on Social Media

Respect for human rights is the cornerstone of strong communities, based on the principles of dignity, equality, and recognition of inherent value of each individual. Domestic Violence, ranging from physical abuse to emotional manipulation, is worldwide considered as the violation of the elementary rights to which all human beings are entitled to. As one might expect, the consequences for its victims are often severe, far-reaching, and long-lasting, causing major health, welfare, and economic burden. Domestic Violence is also one of the most prevailing forms of violence, and due to the social stigma surrounding the issue particularly challenging to address. With the emergence and expansion of Social Media, the substantial shift in the support-seeking and the support-provision pattern has been observed. The initial barriers in approaching healthcare professionals, i.e. personal reservations, or safety concerns, have been effectively addressed by virtual environments. Social Media platforms have quickly become crucial networking hubs for violence survivors as well as at-risk individuals to share experiences, raise concerns, offer advice, or express sympathy. As a result, the specialized support services groups have been established with the aim of pro-active reach-out to potential victims in time-critical situations. Given the high-volume, highvelocity and high-variety of Social Media data, the manual posts evaluation has not only become inefficient, but also unfeasible in the long-term. The conventional automated approaches reliant on pre-defined lexicons, and hand-crafted feature engineering proved limited in their classification performance capability when exposed to the challenging nature of Social Media discourse. At the same time, Deep Learning the state-of-the-art sub-field of Machine Learning has shown remarkable results on text classification tasks. Given its relative recency and algorithmical complexity, the implementation of Deep Learningbased models has been vastly under-utilised in practical applications. In particular, no prior work has addressed the problem of fine-grained user-generated content classification with Deep Learning in Domestic Violence domain. The study introduces novel 3-part framework aimed at (i) binary detection of critical situations; (ii) multi-class content categorization; and (ii) Abuse Types and Health Issues extraction from Social Media discourse. The classification performance of state-of-the-art models is improved through the domain-specific word embeddings development, capable of precise relationships between the words recognition. The prevalent patterns of abuse, and the associated health conditions are efficiently extracted to shed the light on violence scale and severity from directly affected individuals. The approach proposed marks a step forward towards effective prevention and mitigation of violence within the society.
An automated planning strategy for near real-time adaptive proton therapy in prostate cancer

Proton therapy plans are very sensitive to anatomical changes such as density changes along the pencil-beam paths and changes in organ shape and location. Previously, we developed a restoration method which compensates for density changes along the pencil-beam paths but which is unable to adapt for anatomical changes. This study’s purpose is to develop and evaluate an automated method for adaptation of IMPT plans in near real-time to the anatomy of the day. We developed an automated treatment plan adaptation method using (1) a restoration of spot positions (Bragg peaks) by adapting the energies to the new water equivalent path lengths; and (2) a spot addition to fully cover the target of the day, followed by a fast reference point method optimization of the spot weights resulting in a Pareto optimal plan for the daily anatomy. The method was developed and evaluated using 8-10 repeat CT scans of 11 prostate cancer patients, prescribing 55 Gy(RBE) (seminal vesicles and lymph nodes) with a boost to 74 Gy(RBE) (prostate). Applying the automated adaptation method resulted in a clinically acceptable target coverage (V95% 98% and V107% 2%) for 96% of the scans after a single iteration of adding 2500 spots. The other scans obtained target coverages with V95% 98% and 2 < V107% 5%. When using two spot-addition iterations, all scans obtained clinically acceptable results. Compared to the restoration method the adaptation lowered the mean dose to rectum and bladder with median values of 6.2 Gy(RBE) and 4.7 Gy(RBE) respectively. The largest improvements were obtained for V45Gy(RBE) for both rectum and bladder, with median differences of 10.3%-point and 10.8%-point respectively, and maximum differences up to 22%-point. The two adaptation steps took on average 7.3 s and 1.7 min respectively. No user interaction was needed, making this fast and fully automated method a first step towards online adaptive proton therapy.