Miracle-dz/UniFAR-FTUs huggingface dataset:
Preference about Laws for the Legal Recognition of Same-Sex Relationships in Taiwanese People Before and After Same-Sex Marriage Referenda: A Facebook Survey Study

This study examined the factors related to the preference about laws to legalize same-sex relationships in participants of the first wave of a survey (Wave 1, 23 months before the same-sex marriage referendum) and the second wave of a survey (Wave 2, 1 week after the same-sex marriage referendum) in Taiwan. The data of 3286 participants in Wave 1 and 1370 participants in Wave 2 recruited through a Facebook advertisement were analyzed. Each participant completed an online questionnaire assessing their attitude toward the legal recognition of same-sex relationships, preference about laws to legalize same-sex relationships (establishing same-sex couple laws outside the Civil Code vs. changing the Civil Code to include same-sex marriage laws), belief in the importance of legalizing same-sex relationships, and perceived social attitudes toward the legal recognition of same-sex relationships. The results revealed that those who did not support legalizing same-sex relationships were more likely to prefer establishing same-sex couple laws outside the Civil Code than those who supported the legalization. The form of law preferred to legalize same-sex relationships significantly changed between Wave 1 and Wave 2. Multiple factors, including gender, age, sexual orientation, belief in the importance of legalizing same-sex relationships to human rights and the social status of sexual minorities, and perceived peers’ and families’ attitudes toward the legal recognition of same-sex relationships, were significantly associated with the preference of laws, although these associations varied among heterosexual and non-heterosexual participants and at various stages of the survey.
Specific Lhc Proteins Are Bound to PSI or PSII Supercomplexes in the Diatom Thalassiosira pseudonana1[OPEN]

The diatom Thalassiosira pseudonana shows a specific organization of the antenna complexes linked to PSI and PSII, whereby higher oligomeric antenna complexes are only weakly connected. Despite the ecological relevance of diatoms, many aspects of their photosynthetic machinery remain poorly understood. Diatoms differ from the green lineage of oxygenic organisms by their photosynthetic pigments and light-harvesting complex (Lhc) proteins, the latter of which are also called fucoxanthin-chlorophyll proteins (FCP). These are composed of three groups of proteins: Lhcf as the main group, Lhcr that are PSI associated, and Lhcx that are involved in photoprotection. The FCP complexes are assembled in trimers and higher oligomers. Several studies have investigated the biochemical properties of purified FCP complexes, but limited knowledge is available about their interaction with the photosystem cores. In this study, isolation of stable supercomplexes from the centric diatom Thalassiosira pseudonana was achieved. To preserve in vivo structure, the separation of thylakoid complexes was performed by native PAGE and sucrose density centrifugation. Different subpopulations of PSI and PSII supercomplexes were isolated and their subunits identified. Analysis of Lhc antenna composition identified Lhc(s) specific for either PSI (Lhcr 1, 3, 4, 7, 10–14, and Lhcf10) or PSII (Lhcf 1–7, 11, and Lhcr2). Lhcx6_1 was reproducibly found in PSII supercomplexes, whereas its association with PSI was unclear. No evidence was found for the interaction between photosystems and higher oligomeric FCPs, comprising Lhcf8 as the main component. Although the subunit composition of the PSII supercomplexes in comparison with that of the trimeric FCP complexes indicated a close mutual association, the higher oligomeric pool is only weakly associated with the photosystems, albeit its abundance in the thylakoid membrane.
PDI-Mediated Reduction of Disulfide Bond on PSD95 Increases Spontaneous Seizure Activity by Regulating NR2A–PSD95 Interaction in Epileptic Rats Independent of S-Nitrosylation

Postsynaptic density-95 (PSD95), a major scaffolding protein, is critical in coupling N-methyl-D-aspartate receptor (NMDAR) to cellular signaling networks in the central nervous system. A couple of cysteine residues in the N-terminus of PSD95 are potential sites for disulfide bonding, S-nitrosylation and/or palmitoylation. Protein disulfide isomerase (PDI) reduces disulfide bonds (S-S) to free thiol (-SH) on various proteins. However, the involvement of PDI in disulfide bond formation/S-nitrosylation of PSD95 and its role in epilepsy are still unknown. In the present study, acute seizure activity significantly increased the bindings of PDI to NR2A, but not to PSD95, while it decreased the NR2A–PSD95 binding. In addition, pilocarpine-induced seizures increased the amount of nitrosylated (SNO-) thiols, not total (free and SNO-) thiols, on PSD95. Unlike acute seizure, spontaneous seizing rats showed the increases in PDI–PSD95 binding, total- and SNO-thiol levels on PSD95, and NR2A–PSD95 interaction. PDI siRNA effectively reduced spontaneous seizure activity with decreases in total thiol level on PSD95 and NR2A–PSD95 association. These findings indicate that PDI-mediated reduction of disulfide-bond formations may facilitate the NR2A–PSD95 binding and contribute to spontaneous seizure generation in epileptic animals.
Shunting Inhibition Improves Synchronization in Heterogeneous Inhibitory Interneuronal Networks with Type 1 Excitability Whereas Hyperpolarizing Inhibition Is Better for Type 2 Excitability

Abstract All-to-all homogeneous networks of inhibitory neurons synchronize completely under the right conditions; however, many modeling studies have shown that biological levels of heterogeneity disrupt synchrony. Our fundamental scientific question is “how can neurons maintain partial synchrony in the presence of heterogeneity and noise? ” A particular subset of strongly interconnected interneurons, the PV+ fast-spiking (FS) basket neurons, are strongly implicated in γ oscillations and in phase locking of nested γ oscillations to theta. Their excitability type apparently varies between brain regions: in CA1 and the dentate gyrus they have type 1 excitability, meaning that they can fire arbitrarily slowly, whereas in the striatum and cortex they have type 2 excitability, meaning that there is a frequency thresh old below which they cannot sustain repetitive firing. We constrained the models to study the effect of excitability type (more precisely bifurcation type) in isolation from all other factors. We use sparsely connected, heterogeneous, noisy networks with synaptic delays to show that synchronization properties, namely the resistance to suppression and the strength of theta phase to γ amplitude coupling, are strongly dependent on the pairing of excitability type with the type of inhibition. Shunting inhibition performs better for type 1 and hyperpolarizing inhibition for type 2. γ Oscillations and their nesting within theta oscillations are thought to subserve cognitive functions like memory encoding and recall; therefore, it is important to understand the contribution of intrinsic properties to these rhythms.
Identification and Quantification of Transient Receptor Potential Vanilloid 1 (TRPV1) in Equine Articular Tissue

Simple summary Osteoarthritis is affecting several species including the horse. Transient receptor potential vanilloid 1 (TRPV1)—also known as the ‘chili receptor’—is currently being investigated as a target for treating osteoarthritis in humans. To evaluate whether it could be a potential target in treating osteoarthritis in horses, we collected synovial membrane samples from healthy horse joints and horse joints with joint disease to investigate the expression of the TRPV1. Laboratory analysis showed that TRPV1 is present in horse joints, and that the levels might be elevated in diseased joints, even at a chronic state of disease. This means that TRPV1 could be used as a potential target for osteoarthritis treatment in horses. Future studies in this area will not only be beneficial to horses and their owners, but more knowledge about TRPV1, the mode of action, and possible side effects will also benefit translation into human osteoarthritis research. Abstract Joint pain and osteoarthritis (OA) are some of the most common causes of lameness in horses, and most of the available treatments focus on symptomatic relief without a disease-modifying effect. TRPV1 is a potential target for treating joint diseases, including OA, and the present study aims to investigate if the TRPV1 receptor is present in equine articular tissue and determine whether the number of receptors is upregulated in joint inflammation. Metacarpo/metatarsophalangeal (MCP/MTP) joints from 15 horses euthanised for reasons unrelated to this study were included. Based on synovial fluid analysis, macroscopic evaluation, and magnetic resonance imaging (MRI), joints were divided into two groups: healthy joints and joints with pathology. ELISA analysis was performed on synovial tissue harvested from all joints. TPRV1 was found in all joints. The mean concentration of TRPV1 compared to total protein in healthy joints (8.4 × 10−7 ng/mL) and joints with pathology (12.9 × 10−7 ng/mL) differed significantly (p = 0.01, t-test with Welch correction). Quantitative real-time reverse transcriptase PCR analysis was performed on RNA isolates from synovial tissue from all joints. TRPV1 mRNA expression ratio normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in healthy joints (0.16 (SD: 0.19)) and joints with pathology (0.24 (SD: 0.14)) did not differ significantly (p = 0.43, t-test with Welch correction). mRNA expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) was very low for both groups. In conclusion, TRPV1 was detected both on mRNA and the protein level, with a higher expression of TRPV1 in samples from joints with pathology. Future studies will determine the clinical potential of equine TRPV1 as a target in the management of joint pain and inflammation.
A Systematic Methodology to Evaluate Prediction Models for Driving Style Classification

Identifying driving styles using classification models with in-vehicle data can provide automated feedback to drivers on their driving behavior, particularly if they are driving safely. Although several classification models have been developed for this purpose, there is no consensus on which classifier performs better at identifying driving styles. Therefore, more research is needed to evaluate classification models by comparing performance metrics. In this paper, a data-driven machine-learning methodology for classifying driving styles is introduced. This methodology is grounded in well-established machine-learning (ML) methods and literature related to driving-styles research. The methodology is illustrated through a study involving data collected from 50 drivers from two different cities in a naturalistic setting. Five features were extracted from the raw data. Fifteen experts were involved in the data labeling to derive the ground truth of the dataset. The dataset fed five different models (Support Vector Machines (SVM), Artificial Neural Networks (ANN), fuzzy logic, k-Nearest Neighbor (kNN), and Random Forests (RF)). These models were evaluated in terms of a set of performance metrics and statistical tests. The experimental results from performance metrics showed that SVM outperformed the other four models, achieving an average accuracy of 0.96, F1-Score of 0.9595, Area Under the Curve (AUC) of 0.9730, and Kappa of 0.9375. In addition, Wilcoxon tests indicated that ANN predicts differently to the other four models. These promising results demonstrate that the proposed methodology may support researchers in making informed decisions about which ML model performs better for driving-styles classification.
Improving Clinical Islet Transplantation Outcomes

Transplantation of islets purified from donor pancreata is one of only a few clinical strategies that can reverse type 1 diabetes (T1D) and restore glycemic control (1–3). Significant progress has been made by improving transplantation strategies in areas including immune suppressive regimes, islet quality, transplanted β-cell mass and purity, and donor selection (4–6). However, while improved metabolic control and reduced glycemic side effects such as hypoglycemia persist long term in the majority of T1D patients, insulin independence beyond 1 year is only achieved in a minority of cases (2). Early loss of islet mass upon portal vein infusion is believed to have a major negative impact (7). Recurrence of insulitis, the hallmark of T1D immunopathogenesis leading to autoimmune mediated β-cell destruction, and islet allograft rejection pose additional therapeutic hurdles (8,9). Recently, neutrophils were suggested as part of the innate immune system contributing to development of T1D (10). Chemokines produced by distressed islet tissue attract leukocytes to the site of implantation (Fig. 1). The chemokine CXCL8, produced by recruited and resident macrophages, attracts neutrophils carrying its receptors CXCR1/2 to the lesion. In this issue of Diabetes Care , Piemonti and colleagues (11) now report the results of a phase 3 clinical trial assessing whether interference in homing of leukocytes to the implanted islet graft using reparixin, a small molecule that interferes with CXCR1/2 signaling, may improve transplantation outcome. The rationale for this strategy is outstanding. Early studies in mice and humans were very encouraging. Treatment with reparixin prevented and reversed autoimmune diabetes in NOD mice and improved graft survival …
Ephrin or not? Six tough questions on Eph targeting

ABSTRACT Introduction: The Eph-ephrin is a cell-cell communication system generating a forward signal in cell expressing Eph receptors and a reverse signal in ephrin-ligand expressing cells. While clearly involved in the insurgence and progression of cancer, the understanding of the molecular mechanisms regulated by this system needs development; this is a hurdle to the development of therapeutic strategies that can target the Eph receptors and/or their ephrin ligands. Areas covered: We have taken the opportunity to share some key questions on the most effective strategies to target the Eph-ephrin system. This article is based on our experience of the field and therefore is a Perspective and not comprehensive examination of the literature. Expert opinion: Targeting of the Eph-ephrin system has emerged as a potentially valuable approach for cancer therapy. Pharmacological tools have been reported in the last 15 years and these include forward signaling blockers such as kinases inhibitors and antagonists of forward and reverse signaling. Also, biologics including antibodies and recombinant proteins have been developed and some have reached early clinical stages. Data deem the Eph-ephrin system as a signaling axis that is an elusive target. A better understanding of the basic pharmacology behind the activity of available agents and a comprehensive knowledge of the ephrin biology are necessary. We are looking forward to knowing the opinion of the readers.
Perioperative Transfusions and Venous Thromboembolism

In this prospective registry study of >480 000 children, we propose an association between perioperative RBC transfusions and postoperative VTE in children, infants, and neonates. BACKGROUND AND OBJECTIVES: Annual incidence of venous thromboembolism (VTE) including postoperative VTE in hospitalized children is rising significantly. A growing body of evidence supports the role of red blood cells (RBCs) in pathologic thrombosis. In this study, we examined the association of perioperative RBC transfusion with postoperative VTE in pediatric patients. METHODS: The pediatric databases of the American College of Surgeons’ National Surgical Quality Improvement Project from 2012 to 2017 were used. Multivariable logistic regression was used to examine the association between perioperative RBC transfusion status and the development of new or progressive VTE within 30 days of surgery. The analyses were age stratified, as follows: neonates (≤28 days), infants (>28 days and <1 year), and children (≥1 year). RESULTS: In this study, we included 20 492 neonates, 79 744 infants, and 382 862 children. Postoperative development of VTE was reported in 99 (0.48%) neonates, 147 (0.2%) infants, and 374 (0.1%) children. In all age groups, development of VTE was significantly more common among patients with a perioperative RBC transfusion than patients without a perioperative RBC transfusion (neonates: adjusted odds ratio [aOR] = 4.1, 95% confidence interval [CI] = 2.5–6.7; infants: aOR = 2.4, 95% CI = 1.7–3.6; children: aOR = 2.2, 95% CI = 1.7–2.9). Among children who received an intra- or postoperative transfusion, the weight-based volume of RBCs (mL/kg) transfused was associated with postoperative VTE in a dose-dependent manner: second tertile (odds ratio = 2.3, 95% CI = 1.3–4.1) and third tertile (odds ratio = 4.1, 95% CI = 2.3–7.4) versus first tertile. CONCLUSIONS: Perioperative RBC transfusions are independently associated with development of new or progressive postoperative VTE in children, infants, and neonates. These findings need further validation in prospective studies and emphasize the need for evidence-based perioperative pediatric blood transfusion decisions.
Sensitive fluorometric determination of quinclorac residues in rice

ABSTRACT Rice is one of the most important foods in the world due to its high nutritional value and production. Quinclorac, a selective herbicide, is one of the most detected pesticide residues in rice crops according to pesticide monitoring studies. Common methods for the determination of quinclorac in rice are very time-consuming and labour-intensive, so it is important to develop alternative sensitive and simple analytical methods able to detect quinclorac in food samples. Here we propose a fluorometric method for the screening of this herbicide at excitation/emission wavelengths of 238/358 nm/nm, respectively. A modified QuEChERS method was selected for sample treatment due to its simplicity and high recovery yields. The proposed method presents a detection limit of 2.5 ng mL−1 and satisfactory precision. Recovery experiments were performed in different kinds of rice (white and brown) at or below the Maximum Residue Limit established in European Union (5 mg kg−1), obtaining values close to 100%. All these characteristics ensure that the proposed method fulfils the requirements for its application in food control. GRAPHICAL ABSTRACT
Myelofibrosis biology and contemporary management

Myelofibrosis is an enigmatic myeloproliferative neoplasm, despite noteworthy strides in understanding its genetic underpinnings. Driver mutations involving JAK2, CALR or MPL in 90% of patients mediate constitutive JAK‐STAT signaling which, in concert with epigenetic alterations (ASXL1, DNMT3A, SRSF2, EZH2, IDH1/2 mutations), play a fundamental role in disease pathogenesis. Aberrant immature megakaryocytes are a quintessential feature, exhibiting reduced GATA1 protein expression and secreting a plethora of pro‐inflammatory cytokines (IL‐1 ß, TGF‐ß), growth factors (b‐FGF, PDGF, VEGF) in addition to extra cellular matrix components (fibronectin, laminin, collagens). The ensuing disrupted interactions amongst the megakaryocytes, osteoblasts, endothelium, stromal cells and myofibroblasts within the bone marrow culminate in the development of fibrosis and osteosclerosis. Presently, prognostic assessment tools for primary myelofibrosis (PMF) are centered on genetics, with incorporation of cytogenetic and molecular information into the mutation‐enhanced (MIPSS 70‐plus version 2.0) and genetically‐inspired (GIPSS) prognostic scoring systems. Both models illustrate substantial clinical heterogeneity in PMF and serve as the crux for risk‐adapted therapeutic decisions. A major challenge remains the dearth of disease‐modifying drugs, whereas allogeneic transplant offers the chance of long‐term remission for some patients. Our review serves to synopsise current appreciation of the pathogenesis of myelofibrosis together with emerging management strategies.
OP07 Might ambulance service organisational culture affect ambulance non conveyance rates?

Background Ambulance services are experiencing increasing demand for response to emergency calls. In response, they have increased the proportion of patients not conveyed to an emergency department (ED). Alternatives to transporting patients to an ED include the provision of telephone advice only (‘hear and treat’), treatment at the scene (‘see and treat’) and transport to another facility (‘see and convey elsewhere’). There is considerable variation in the rates of different types of non-conveyance, and in non-conveyance overall, between ambulance services in England. Understanding of the reasons for this variation has been limited and relatively unexplored. We will explore if there is variability in perceptions of the organisational culture within each individual ambulance service and show this in the context of non conveyance rates. Methods We undertook 50 qualitative telephone interviews with ambulance service providers and commissioners in the 10 larger ambulance services in England, to identify factors that may explain variation in rates of ambulance non-conveyance. Data was analysed using a Framework model. Results Amongst interviewees there was variation in the perceptions they held regarding the organisational culture of the ambulance service which they were employed by. Recent management restructuring within the ambulance service, perception of management support across the organisation, motivation of the organisation to undertake non conveyance, and perceptions of support for staff undertaking non conveyance varied across the 10 ambulance services. We will present this qualitative data alongside routine data identifying non conveyance rates in each service, and explore whether organisational culture appears to be related to ambulance non conveyance rates. Implications Organisational culture is a complex issue but one which is potentially modifiable. Building a greater understanding of ambulance service organisational culture and how this relates to ambulance non conveyance may help identify ways of improving service delivery across all ambulance services.
Modeling Favipiravir Antiviral Efficacy Against Emerging Viruses: From Animal Studies to Clinical Trials

In 2014, our research network was involved in the evaluation of favipiravir, an anti‐influenza polymerase inhibitor, against Ebola virus. In this review, we discuss how mathematical modeling was used, first to propose a relevant dosing regimen in humans, and then to optimize its antiviral efficacy in a nonhuman primate (NHP) model. The data collected in NHPs were finally used to develop a model of Ebola pathogenesis integrating the interactions among the virus, the innate and adaptive immune response, and the action of favipiravir. We conclude the review of this work by discussing how these results are of relevance for future human studies in the context of Ebola virus, but also for other emerging viral diseases for which no therapeutics are available.