Miracle-dz/UniFAR-FTUs huggingface dataset:
Signal Transduction by Reactive Oxygen and Nitrogen Species (Eds Henry J. Forman, Jon Fukuto and Martine Torres)

All organisms living aerobically are continually exposed to metabolites of oxygen. These metabolites, known as reactive oxygen species (ROS), include the superoxide anion (O2 ), hydroxyl radical, and hydrogen peroxide. Normally such species are eliminated through a delicate redox balance involving antioxidants such as glutathione and a variety of phase II enzymes such as NAD(P)H. However if this balance is disturbed, accumulation of ROS can lead to a variety of diseases including cancer, diabetes, and Alzheimer’s. ROS and reactive nitrogen species (RNS) are however not simply unwanted metabolic by-products of oxygen metabolism, as they are also involved in the process of shuttling information within cells—so-called signal transduction. The first such species unequivocally demonstrated to be involved in signal transduction was the free radical nitric oxide (NO) in the process of vasodilation, though its role in neurotransmission, inhibition of platelet aggregation, and post-translational modification of proteins, amongst others has been subsequently demonstrated. Potential roles for many of the ROS and RNS detected in cells, predominantly in the processes of cellular proliferation, differentiation, and apoptosis, have since been postulated. The elucidation of the biochemical roles these short-lived species (1–1000 ns) play in organisms, and the mechanisms by which they are created and destroyed, is a complex and multidisciplinary task. The aim of this excellent 400-page book is to give the current (to mid-2002) understanding of many aspects of ROS and RNS in signal transduction and disease processes. The book is divided into three sections covering basic chemical principles of ROS and RNS signalling (5 chapters), more thorough discussion covering various specific processes of ROS and RNS signalling (9 chapters), and the physiology and pathophysiology resulting from these processes (6 chapters). The initial chapters provide a good framework for understanding the subsequent chapters’more specific discussions, though each chapter is a complete whole and can be read in isolation. A book with 20 chapters, each written by different authors, is bound to have some repetition, and that occurs in this work as well. Chemists may find the lack of molecular structures annoying, and a list of abbreviations would also have been useful. However the main problem with this book is the inadequate index which lists, for a limited selection of keywords, only the pages upon which they occur and not their context. This is particularly frustrating for a volume that will be a very useful reference work for some time for those working in the field or in related areas.
Analysis of inappropriate prescribing in elderly patients of the Swiss HIV Cohort Study reveals gender inequity.

BACKGROUND The extent of inappropriate prescribing observed in geriatric medicine has not been thoroughly evaluated in people ageing with HIV. We determined the prevalence of and risk factors for inappropriate prescribing in individuals aged ≥75 years enrolled in the Swiss HIV Cohort Study. METHODS Retrospective review of medical records was performed to gain more insights into non-HIV comorbidities. Inappropriate prescribing was screened using the Beers criteria, the STOPP/START criteria and the Liverpool drug-drug interactions (DDIs) database. RESULTS For 175 included individuals, the median age was 78 years (IQR 76-81) and 71% were male. The median number of non-HIV comorbidities was 7 (IQR 5-10). The prevalence of polypharmacy and inappropriate prescribing was 66% and 67%, respectively. Overall, 40% of prescribing issues could have deleterious consequences. Prescribing issues occurred mainly with non-HIV drugs and included: incorrect dosage (26%); lack of indication (21%); prescription omission (drug not prescribed although indicated) (17%); drug not appropriate in elderly individuals (18%) and deleterious DDIs (17%). In the multivariable logistic regression, risk factors for prescribing issues were polypharmacy (OR: 2.5; 95% CI: 1.3-4.7), renal impairment (OR: 2.7; 95% CI: 1.4-5.1), treatment with CNS-active drugs (OR: 2.1; 95% CI: 1.1-3.8) and female sex (OR: 8.3; 95% CI: 2.4-28.1). CONCLUSIONS Polypharmacy and inappropriate prescribing are highly prevalent in elderly people living with HIV. Women are at higher risk than men, partly explained by sex differences in the occurrence of non-HIV comorbidities and medical care. Medication reconciliation and periodic review of prescriptions by experienced physicians could help reduce polypharmacy and inappropriate prescribing in this vulnerable, growing population.
A Ten Years Monitoring of Chlorofluorocarbons at the Antarctica: Results and Perspectives

Abstract Chlorofluorocarbons are man-made long lasting atmospheric pollutants of great environmental concern, responsible for important global change phenomena. Recently, they were replaced by hydrogenated halocarbons that, even if less persistent, do not lack in environmental impact. Atmospheric concentrations of these compounds were measured in Antarctica by gas chromatography. The extremely low atmospheric mixing ratios of these compounds require a pre-concentration step of the air sample on suitable adsorbent in order to meet the sensitivity of the analytical method Results obtained analyzing air samples collected in Antarctica since 1988 for the determination of CFC-12 and CFC-11 are reported, together with data concerning the less abundant species.
Acclimation of leaf photosynthesis and respiration to warming in field-grown wheat.

Climate change and future warming will significantly affect crop yield. The capacity of crops to dynamically adjust physiological processes (i.e. acclimate) to warming might improve overall performance. Understanding and quantifying the degree of acclimation in field crops could ensure better parameterization of crop and Earth System models and predictions of crop performance. We hypothesized that for field-grown wheat, when measured at a common temperature (25°C), crops grown under warmer conditions would exhibit acclimation, leading to enhanced crop performance and yield. Acclimation was defined as: (i) decreased rates of net photosynthesis at 25°C (A25 ) coupled with lower maximum carboxylation capacity (Vcmax 25 ); (ii) reduced leaf dark respiration at 25°C (both in terms of O2 consumption, Rdark _O2 25 ; and CO2 efflux, Rdark _CO2 25 ); and (iii) lower Rdark _CO2 25 :Vcmax 25 . Field experiments were conducted over two seasons with 20 wheat genotypes, sown at three different planting dates, to test these hypotheses. Leaf-level CO2 based traits (A25 , Rdark _CO2 25 , and Vcmax 25 ) did not show the classic acclimation responses that we hypothesized; by contrast, the hypothesized changes in Rdark_ O2 were observed. These findings have implications for predictive crop models that assume similar temperature response among these physiological processes, and for predictions of crop performance in a future warmer world. This article is protected by copyright. All rights reserved.
Modeling Conversational Structure to improve Conversational Question Answering

Students often gain knowledge by asking questions via conversation. In a conversation of two people asking and answering questions based on a context, although the questions can be very vague, human can still understand the vague question given the conversation history. In this project, we work on the task Conversational Question Answering (CoQA). We want to understand the question and context better by implicitly and explicitly modeling the structure of dialogue history. We found dialogue history aware context representation is very useful for answer prediction, while the history aware question embedding did not affect the overall performance. Our best model achieved 76 . 9 F1 score on development set.
Single crystalline GaSe/WSe2 heterointerfaces grown by van der Waals epitaxy. II. Junction characterization

The junction properties of GaSe/WSe2 heterointerfaces grown by van der Waals epitaxy have been characterized by photoelectron spectroscopy and surface photovoltage measurements (SPV). The surfaces of p‐WSe2 substrates doped with Se excess convert to n doping during annealing at T≥720 K, leading to a SPV of 330 mV. Deposited p GaSe forms an n‐p heterodiode opposing the p‐n homodiode within the substrate. Promising results are obtained for n‐WSe2/p‐GaSe heterointerfaces with SPV of at least 0.3 eV. The valence band and conduction band offsets are 0.6 and 0.2±0.1 eV, respectively, in accordance with the Anderson model of heterojunction formation.
Public Response to a Social Media Tobacco Prevention Campaign: Content Analysis

Background Prior research suggests that social media–based public health campaigns are often targeted by countercampaigns. Objective Using reactance theory as the theoretical framework, this research characterizes the nature of public response to tobacco prevention messages disseminated via a social media–based campaign. We also examine whether agreement with the prevention messages is associated with comment tone and nature of the contribution to the overall discussion. Methods User comments to tobacco prevention messages, posted between April 19, 2017 and July 12, 2017, were extracted from Twitter, Facebook, and Instagram. Two coders categorized comments in terms of tone, agreement with message, nature of contribution, mentions of government agency and regulation, promotional or spam comments, and format of comment. Chi-square analyses tested associations between agreement with the message and tone of the public response and the nature of contributions to the discussions. Results Of the 1242 comments received (Twitter: n=1004; Facebook: n=176; Instagram: n=62), many comments used a negative tone (42.75%) and disagreed with the health messages (39.77%), while the majority made healthy contributions to the discussions (84.38%). Only 0.56% of messages mentioned government agencies, and only 0.48% of the comments were antiregulation. Comments employing a positive tone (84.13%) or making healthy contributions (69.11%) were more likely to agree with the campaign messages (P=0.01). Comments employing a negative tone (71.25%) or making toxic contributions (36.26%) generally disagreed with the messages (P=0.01). Conclusions The majority of user comments in response to a tobacco prevention campaign made healthy contributions. Our findings encourage the use of social media to promote dialogue about controversial health topics such as smoking. However, toxicity was characteristic of comments that disagreed with the health messages. Managing negative and toxic comments on social media is a crucial issue for social media–based tobacco prevention campaigns to consider.
Clinical relevance of NKT cells and soluble MIC-A in Hodgkin lymphoma

Abstract Previous studies demonstrated that the majority of Hodgkin lymphoma (HL) patients achieve response after treatment, while 5% become refractory. Studies analyzing the role of lymphocyte subsets in peripheral blood are limited. This investigation sought to evaluate peripheral blood lymphocyte subsets and soluble MHC class I chain-related proteins A and B (sMIC-A/B) and their correlation with survival in patients with newly diagnosed HL. The study recruited 36 patients and 72 healthy donors. HL patients showed a decrease in CD4, B, monocytes, NK, and NKT cells; and an increase in γ-δ T cells and soluble MIC-A serum levels. Higher values of s-MIC-A >100 ng/mL and NKT cells >40 µL correlated with poor overall survival (OS). In conclusion, in HL peripheral blood CD4 T and B cells, monocytes, NK, and NKT cells were decreased, while s-MIC-A and γ-δ T cells increased. Higher values of s-MIC-A and NKT cells correlated with poor survival.
Nanoparticles in pregnancy: the next frontier in reproductive therapeutics.

BACKGROUND Nanotechnology involves the engineering of structures on a molecular level. Nanomedicine and nano-delivery systems have been designed to deliver therapeutic agents to a target site or organ in a controlled manner, maximizing efficacy while minimizing off-target effects of the therapeutic agent administered. In both reproductive medicine and obstetrics, developing innovative therapeutics is often tempered by fears of damage to the gamete, embryo or developing foetus or of negatively impacting a woman's reproductive potential. Thus, nanomedicine delivery systems may provide alternative targeted intervention strategies, treating the source of the disease and minimizing long-term consequences for the mother and/or her foetus. OBJECTIVE AND RATIONALE This review summarizes the current state of nanomedicine technology in reproductive medicine and obstetrics, including safety, potential applications, future directions and the hurdles for translation. SEARCH METHODS A comprehensive electronic literature search of PubMed and Web of Science databases was performed to identify studies published in English up until February 2020. Relevant keywords were used to obtain information regarding use of nanoparticle technology in fertility and gene therapy, early pregnancy complications (ectopic pregnancy and gestational trophoblastic disease) and obstetric complications (preeclampsia, foetal growth restriction, preterm birth and gestational diabetes) and for selective treatment of the mother or foetus. Safety of specific nanoparticles to the gamete, embryo and foetus was also investigated. OUTCOMES Pre-clinical research in the development of nanoparticle therapeutic delivery is being undertaken in many fields of reproductive medicine. Non-hormonal-targeted nanoparticle therapy for fibroids and endometriosis may provide fertility-sparing medical management. Delivery of interventions via nanotechnology provides opportunities for gene manipulation and delivery in mammalian gametes. Targeting cytotoxic treatments to early pregnancy tissue provides an alternative approach to manage ectopic pregnancies and gestational trophoblastic disease. In pregnancy, nanotherapeutic delivery offers options to stably deliver silencing RNA and microRNA inhibitors to the placenta to regulate gene expression, opening doors to novel genetic treatments for preeclampsia and foetal growth restriction. Restricting delivery of teratogenic drugs to the maternal compartment (such as warfarin) may reduce risks to the foetus. Alternatively, targeted delivery of drugs to the foetus (such as those to treat foetal arrythmias) may minimize side effects for the mother. WIDER IMPLICATIONS We expect that further development of targeted therapies using nanoparticles in a reproductive setting has promise to eventually allow safe and directed treatments for conditions impacting the health and reproductive capacity of women and for the management of pregnancy and serious pregnancy complications.
Urinary metabolite quantitative trait loci in children and their interaction with dietary factors.

Human metabolism is influenced by genetic and environmental factors. Previous studies have identified over 23 loci associated with more than 26 urine metabolites levels in adults, known as urinary metabolite quantitative trait loci or metabQTLs. The aim of the present study is the identification for the first time of urinary metabQTLs in children and their interaction with dietary patterns. Association between genome-wide genotyping data and 44 urine metabolite levels measured by 1H NMR was tested in 996 children from the Human Early Life Exposome (HELIX) project. Twelve statistically significant urine metabQTLs were identified, involving 11 unique loci and 10 different metabolites. Comparison with previous findings in adults revealed that six metabQTLs were already known, one had been described in serum and three involved the same locus as other reported metabQTLs but different urinary metabolites. The remaining two metabQTLs represent novel urine metabolite-locus associations, reported for the first time in this study (SNP rs12575496 for taurine, and the missense SNP rs2274870 for 3-hydroxyisobutyrate). Moreover, it was found that urinary taurine levels were affected by the combined action of genetic variation and dietary patterns of meat intake, as well as by the interaction of this SNP with beverage intake dietary patterns. Overall, we identified 12 urinary metabQTLs in children, including two novel associations. While a substantial part of the identified loci affected urinary metabolite levels both in children and in adults, the metabQTL for taurine seemed to be specific to children and interacted with dietary patterns.
Mitral annulus disjunction is associated with adverse outcome in Marfan and Loeys–Dietz syndromes

Abstract Aims We aimed to assess the prevalence of mitral annulus disjunction (MAD) and to explore the association with aortic disease and mitral valve surgery in patients with Marfan syndrome (MFS) and Loeys–Dietz syndrome (LDS). Methods and results We included consecutive MFS patients fulfilling Revised Ghent Criteria and LDS patients fulfilling Loeys–Dietz Revised Nosology. MAD was identified by echocardiography and was quantified as the longitudinal distance from the ventricular myocardium to the hinge point of the posterior mitral leaflet. Aortic events were defined as aortic dissection or prophylactic aortic surgery. We recorded the need of mitral valve surgery including mitral valve repair or replacement. We included 168 patients (103 with MFS and 65 with LDS). The prevalence of MAD was 41%. MAD was present in all age groups. Aortic events occurred in 112 (67%) patients (27 with dissections and 85 with prophylactic surgical interventions). Patients with MAD were younger at aortic event than those without MAD (log rank = 0.02) Patients with aortic events had greater MAD distance in posterolateral wall [8 (7–10) mm vs. 7 (6–8) mm, P = 0.04]. Mitral events occurred more frequently in patients with MAD (P < 0.001). Conclusion MAD was highly prevalent in patients with MFS and LDS. MAD was a marker of severe disease including aortic events at younger age and need of mitral valve surgery. Screening patients with MFS an LDS for MAD may provide prognostic information and may be relevant in planning surgical intervention. Detection of MAD in patients with MFS and LDS may infer closer clinical follow-up from younger age.
Pennsylvania coordinated specialty care programs for first‐episode psychosis: 6‐ and 12‐month outcomes

Pennsylvania (PA) first‐episode psychosis (FEP) program evaluation is a statewide initiative, supported by the PA Office of Mental Health and Substance Abuse Services (PA‐OMHSAS) and administered by PA Early Intervention Center/Heads Up, which evaluates fidelity and outcomes of PA Coordinated Specialty Care (CSC) programs. Programs participate in standard computerized measures of CSC outcomes using centralized informatics. The aims of the current report are to describe implementation of this core battery for program evaluation in PA and to present 6‐ and 12‐month outcomes.
Treatment targets in SLE: remission and low disease activity state

Abstract Treat-to-target strategies have changed the approach to management of many chronic conditions, with improvements in patient outcomes. The key to success of treat to target is the availability of validated treatment endpoints, which have been difficult to derive for SLE, a condition notorious for its heterogeneity. This review will focus on the development and validation of the definitions of remission in SLE framework and the lupus low disease activity state. Lupus low disease activity state is more attainable than remission, with a stepwise concentric relationship between the target states indicating increasing stringency. Both lupus low disease activity state and definitions of remission in SLE remission have been proven to be associated with reduction in disease flares, reduced risk of accrual of irreversible end organ damage, and improvement in patient reported outcomes. These endpoints have therefore provided the key for the development of a treat-to-target approach in clinical practice in SLE and for the design of future clinical trials.
Evidence for BMP‐mediated specification of primordial germ cells in an indirect‐developing hemichordate

Primordial germ cells (PGCs) are specified during development by either one of two major mechanisms, the preformation mode or the inductive mode. Because the inductive mode is widely employed by many bilaterians and early branching metazoan lineages, it has been postulated as an ancestral mechanism. However, among the deuterostome species that have been studied, invertebrate chordates use the preformation mode, while many vertebrate and echinoderm species are known to utilize an inductive mechanism, thus leaving the evolutionary history of PGC specification in the deuterostome lineage unclear. Hemichordates are the sister phylum of echinoderms, and together they form a clade called Ambulacraria that represents the closest group to the chordates. Thus, research in hemichordates is highly informative for resolving this issue. In this study, we investigate the developmental process of PGCs in an indirect‐developing hemichordate, Ptychodera flava. We show that maternal transcripts of the conserved germline markers vasa, nanos, and piwi1 are ubiquitously distributed in early P. flava embryos, and these genes are coexpressed specifically in the dorsal hindgut starting from the gastrula stage. Immunostaining revealed that Vasa protein is concentrated toward the vegetal pole in early P. flava embryos, and it is restricted to cells in the dorsal hindgut of gastrulae and newly hatched larvae. The Vasa‐positive cells later contribute to the developing trunk coeloms of the larvae and eventually reside in the adult gonads. We further show that bone morphogenetic protein (BMP) signaling is required to activate expression of the germline determinants in the gastrula hindgut, suggesting that PGC specification is induced by BMP signaling in P. flava. Our data support the hypothesis that the inductive mode is a conserved mechanism in Ambulacraria, which might even trace back to the common ancestor of Deuterostomes.
Stepwise crosstalk between aberrant Nf1, Tp53 and Rb signalling pathways induces gliomagenesis in zebrafish

Abstract The molecular pathogenesis of glioblastoma indicates that RTK/Ras/PI3K, RB and TP53 pathways are critical for human gliomagenesis. Here, several transgenic zebrafish lines with single or multiple deletions of nf1, tp53 and rb1 in astrocytes, were established to genetically induce gliomagenesis in zebrafish. In the mutant with a single deletion, we found only the nf1 mutation low-efficiently induced tumour incidence, suggesting that the Nf1 pathway is critical for the initiation of gliomagenesis in zebrafish. Combination of mutations, nf1;tp53 and rb1;tp53 combined knockout fish, showed much higher tumour incidences, high-grade histology, increased invasiveness, and shortened survival time. Further bioinformatics analyses demonstrated the alterations in RTK/Ras/PI3K, cell cycle, and focal adhesion pathways, induced by abrogated nf1, tp53, or rb1, were probably the critical stepwise biological events for the initiation and development of gliomagenesis in zebrafish. Gene expression profiling and histological analyses showed the tumours derived from zebrafish have significant similarities to the subgroups of human gliomas. Furthermore, temozolomide treatment effectively suppressed gliomagenesis in these glioma zebrafish models, and the histological responses in temozolomide-treated zebrafish were similar to those observed in clinically treated glioma patients. Thus, our findings will offer a potential tool for genetically investigating gliomagenesis and screening potential targeted anti-tumour compounds for glioma treatment.