bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Hawaii public education programme for rat lungworm disease prevention
Authors: Howe Kathleen , Bernal Lydi Morgan , Brewer Frances Kinslow , Millikan Deborah , Jarvi Susan 
Published: August 2020

AbstractEducation is essential for lowering cases of Angiostrongyliasis in Hawaii. A professional development course on rat lungworm disease (RLWD) prevention was offered to Hawaii K-12 teachers during the 2018–2019 school year. Fourteen teachers, 11 from Hawaii Island and three from Maui, representing grades K, 2, 6–8, and 10−12, completed workshops and activities and received course credit. Teachers reached 652 students and educated 86 teachers and staff and approximately 900 community members including parents. A pre-course survey showed 55% of teachers agreed to a basic understanding of rat lungworm and its impact on Hawaii; this increased to 100% post-course. A sixth-grade class was the first to document the arrival of a highly competent intermediate host of the rat lungworm in a new location, an important discovery that initiated community awareness and control efforts. Six, 1-day workshops were held in 2018–2019, each on one of the main Hawaiian Islands. These were attended by 106 participants including teachers, community educators, and interested individuals from agencies, non-profits, businesses and the private sector. Of participants surveyed, 100% responded the workshop improved their overall understanding of RLWD. Efforts are being made to continue these programmes.
RSA reactivity to parent-child conflict as a predictor of dysregulated emotion and behavior in daily life
Authors: Byrd Amy L. , Vine Vera , Beeney Joseph E. , Scott Lori N. , Jennings J. Richard , Stepp Stephanie D. 
Published: August 2020

AbstractBackgroundIndividual variability in tonic (resting) and phasic (reactivity) respiratory sinus arrhythmia (RSA) may underlie risk for dysregulated emotion and behavior, two transdiagnostic indicators that permeate most psychological disorders in youth. The interaction between tonic and phasic RSA may specify unique physiological profiles during the transition to adolescence. The current study utilized clinically referred youth (Mage= 12.03;s.d.= 0.92) to examine baseline RSA, RSA reactivity, and their interaction as predictors of dysregulated emotion and behavior in daily life.MethodParticipants were 162 youth (47% female; 60% minority) in psychiatric treatment for any mood or behavior problem. RSA was assessed during three, 2-minute baselines and an 8-minute parent-child conflict discussion task. Dysregulated emotion and behavior were assessed during a 4-day ecological momentary assessment protocol that included 10 time-based prompts over a long weekend.ResultsGreater RSA withdrawal to the conflict was associated with dysregulated basic emotion (sadness, anger, nervousness, stress) in daily life. Two distinct interactions also emerged, such that baseline RSA was related to dysregulated complex emotion (shame, guilt, loneliness, emptiness) and dysregulated behavior as a function of RSA reactivity to conflict. Lower baseline RSA and greater RSA withdrawal were associated with dysregulated complex emotion, while higher baseline RSA and greater RSA withdrawal were associated with dysregulated behavior.ConclusionsFindings point to physiological profiles that increase the risk of dysregulated emotion and behavior during the transition to adolescence. Excessive RSA withdrawal uniquely, and in combination with baseline RSA, increased risk for dysregulation in daily life, underscoring the role of autonomic stress responding as a risk factor for psychopathology.
From Social Investment to Investing in the Social: Insiders’ Perceptions, Experiences, and Expectations
Authors: POSTAN-AIZIK DASSI , STRIER RONI 
Published: August 2020

AbstractSocial investment is a policy approach intended to promote the social inclusion of excluded individuals and groups, mainly through labour market participation and long-term human capital development. Since the 1980’s this approach has spread from Europe worldwide and is now regarded as the latest shift from both ‘traditional’ welfare and the unrestrained neoliberal policy implemented under the austerity regime of the last decades. Most social investment studies focus on the social and economic impacts of policy at the macro-level. This article takes a different perspective to examine how members of excluded communities experience social investment policy in their daily lives. The study analyzes qualitative data collected from a purposive sample of 96 participants from excluded communities in the North of Israel. Findings indicate that participants strongly support social investment ideas of inclusion via human capital development and the labour market. However, their experiences in both areas point to continued struggles with social mechanisms that marginalize them and reinforce multigenerational exclusion. Findings affirm critique of social investment when implemented without major structural changes. The study implications for policy suggest that, without such changes, the paradigmatic promises of social investment may further entrench social exclusion by replicating discriminatory and oppressive practices.
EU mental health governance and citizen participation: a global governmentality perspective
Authors: Edquist Kristin 
Published: August 2020

AbstractOver the last three decades, a system of European Union mental health governance (EUMHG) emerged, via instruments including strategies for action, joint actions, pacts and high-level expert groups. It sponsored multiple projects, initiatives and research, and involved state, non-state and European institutional actors. This paper attempts to understand how EUMHG operated and the structure of political relations within it, attending especially to opportunities for citizen participation. It adopts a global governmentality approach that focuses on practices and discourses. It finds that EUMHG practices including benchmarks, best practices and risk-thinking reinforced larger EU policy goals of market-optimisation, and that the central discourses of de-institutionalisation (DI) and community mental health (CMH) shifted meaning over time, first apprehending mental health as a public-health goal, then targeting mental ill-health as a burden to states. Finally, it finds that non-governmental organisations' (NGOs) work within EUMHG rendered them both objects and subjects of government. Through these dynamics, citizens usually were positioned outside governance, and NGO identities were altered, though CMH's transformative potential remained. Citizen participation in EUMHG was heavily conditioned. NGO and citizen power will need vigilant protection in any future EUMHG.
Galectin-3 favours tumour metastasis via the activation of β-catenin signalling in hepatocellular carcinoma
Authors: Song Mengjia , Pan Qiuzhong , Yang Jieying , He Junyi , Zeng Jianxiong , Cheng Shaoyan , Huang Yue , Zhou Zi-Qi , Zhu Qian , Yang Chaopin , Han Yulong , Tang Yan , Chen Hao , Weng De-Sheng , Xia Jian-Chuan 
Published: August 2020

Abstract
Background
High probability of metastasis limited the long-term survival of patients with hepatocellular carcinoma (HCC). Our previous study revealed that Galectin-3 was closely associated with poor prognosis in HCC patients.

Methods
The effects of Galectin-3 on tumour metastasis were investigated in vitro and in vivo, and the underlying biological and molecular mechanisms involved in this process were evaluated.

Results
Galectin-3 showed a close correlation with vascular invasion and poor survival in a large-scale study in HCC patients from multiple sets. Galectin-3 was significantly involved in diverse metastasis-related processes in HCC cells, such as angiogenesis and epithelial-to-mesenchymal transition (EMT). Mechanistically, Galectin-3 activated the PI3K-Akt-GSK-3β-β-catenin signalling cascade; the β-catenin/TCF4 transcriptional complex directly targeted IGFBP3 and vimentin to regulate angiogenesis and EMT, respectively. In animal models, Galectin-3 enhanced the tumorigenesis and metastasis of HCC cells via β-catenin signalling. Moreover, molecular deletion of Galectin-3-β-catenin signalling synergistically improved the antitumour effect of sorafenib.

Conclusions
The Galectin-3-β-catenin-IGFBP3/vimentin signalling cascade was determined as a central mechanism controlling HCC metastasis, providing possible biomarkers for predicating vascular metastasis and sorafenib resistance, as well as potential therapeutic targets for the treatment of HCC patients.
Identifying proteins bound to native mitotic ESC chromosomes reveals chromatin repressors are important for compaction
Authors: Djeghloul Dounia , Patel Bhavik , Kramer Holger , Dimond Andrew , Whilding Chad , Brown Karen , Kohler Anne-Céline , Feytout Amelie , Veland Nicolas , Elliott James , Bharat Tanmay A. M. , Tarafder Abul K. , Löwe Jan , Ng Bee L. , Guo Ya , Guy Jacky , Huseyin Miles K. , Klose Robert J. , Merkenschlager Matthias , Fisher Amanda G. 
Published: August 2020

AbstractEpigenetic information is transmitted from mother to daughter cells through mitosis. Here, to identify factors that might play a role in conveying epigenetic memory through cell division, we report on the isolation of unfixed, native chromosomes from metaphase-arrested cells using flow cytometry and perform LC-MS/MS to identify chromosome-bound proteins. A quantitative proteomic comparison between metaphase-arrested cell lysates and chromosome-sorted samples reveals a cohort of proteins that were significantly enriched on mitotic ESC chromosomes. These include pluripotency-associated transcription factors, repressive chromatin-modifiers such as PRC2 and DNA methyl-transferases, and proteins governing chromosome architecture. Deletion of PRC2, Dnmt1/3a/3b or Mecp2 in ESCs leads to an increase in the size of individual mitotic chromosomes, consistent with de-condensation. Similar results were obtained by the experimental cleavage of cohesin. Thus, we identify chromosome-bound factors in pluripotent stem cells during mitosis and reveal that PRC2, DNA methylation and Mecp2 are required to maintain chromosome compaction.
HIF-1α and HIF-2α differently regulate tumour development and inflammation of clear cell renal cell carcinoma in mice
Authors: Hoefflin Rouven , Harlander Sabine , Schäfer Silvia , Metzger Patrick , Kuo Fengshen , Schönenberger Désirée , Adlesic Mojca , Peighambari Asin , Seidel Philipp , Chen Chia-yi , Consenza-Contreras Miguel , Jud Andreas , Lahrmann Bernd , Grabe Niels , Heide Danijela , Uhl Franziska M. , Chan Timothy A. , Duyster Justus , Zeiser Robert , Schell Christoph , Heikenwalder Mathias , Schilling Oliver , Hakimi A. Ari , Boerries Melanie , Frew Ian J. 
Published: August 2020

AbstractMutational inactivation of VHL is the earliest genetic event in the majority of clear cell renal cell carcinomas (ccRCC), leading to accumulation of the HIF-1α and HIF-2α transcription factors. While correlative studies of human ccRCC and functional studies using human ccRCC cell lines have implicated HIF-1α as an inhibitor and HIF-2α as a promoter of aggressive tumour behaviours, their roles in tumour onset have not been functionally addressed. Herein we show using an autochthonous ccRCC model that Hif1a is essential for tumour formation whereas Hif2a deletion has only minor effects on tumour initiation and growth. Both HIF-1α and HIF-2α are required for the clear cell phenotype. Transcriptomic and proteomic analyses reveal that HIF-1α regulates glycolysis while HIF-2α regulates genes associated with lipoprotein metabolism, ribosome biogenesis and E2F and MYC transcriptional activities. HIF-2α-deficient tumours are characterised by increased antigen presentation, interferon signalling and CD8+ T cell infiltration and activation. Single copy loss of HIF1A or high levels of HIF2A mRNA expression correlate with altered immune microenvironments in human ccRCC. These studies reveal an oncogenic role of HIF-1α in ccRCC initiation and suggest that alterations in the balance of HIF-1α and HIF-2α activities can affect different aspects of ccRCC biology and disease aggressiveness.
Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains
Authors: La Sala Grégory , Michiels Camille , Kükenshöner Tim , Brandstoetter Tania , Maurer Barbara , Koide Akiko , Lau Kelvin , Pojer Florence , Koide Shohei , Sexl Veronika , Dumoutier Laure , Hantschel Oliver 
Published: August 2020

AbstractThe transcription factor STAT3 is frequently activated in human solid and hematological malignancies and remains a challenging therapeutic target with no approved drugs to date. Here, we develop synthetic antibody mimetics, termed monobodies, to interfere with STAT3 signaling. These monobodies are highly selective for STAT3 and bind with nanomolar affinity to the N-terminal and coiled-coil domains. Interactome analysis detects no significant binding to other STATs or additional off-target proteins, confirming their exquisite specificity. Intracellular expression of monobodies fused to VHL, an E3 ubiquitin ligase substrate receptor, results in degradation of endogenous STAT3. The crystal structure of STAT3 in complex with monobody MS3-6 reveals bending of the coiled-coil domain, resulting in diminished DNA binding and nuclear translocation. MS3-6 expression strongly inhibits STAT3-dependent transcriptional activation and disrupts STAT3 interaction with the IL-22 receptor. Therefore, our study establishes innovative tools to interfere with STAT3 signaling by different molecular mechanisms.
Deployable CRISPR-Cas13a diagnostic tools to detect and report Ebola and Lassa virus cases in real-time
Authors: Barnes Kayla G. , Lachenauer Anna E. , Nitido Adam , Siddiqui Sameed , Gross Robin , Beitzel Brett , Siddle Katherine J. , Freije Catherine A. , Dighero-Kemp Bonnie , Mehta Samar B. , Carter Amber , Uwanibe Jessica , Ajogbasile Fehintola , Olumade Testimony , Odia Ikponmwosa , Sandi John Demby , Momoh Mambu , Metsky Hayden C. , Boehm Chloe K. , Lin Aaron E. , Kemball Molly , Park Daniel J. , Branco Luis , Boisen Matt , Sullivan Brian , Amare Mihret F. , Tiamiyu Abdulwasiu B. , Parker Zahra F. , Iroezindu Michael , Grant Donald S. , Modjarrad Kayvon , Myhrvold Cameron , Garry Robert F. , Palacios Gustavo , Hensley Lisa E. , Schaffner Stephen F. , Happi Christian T. , Colubri Andres , Sabeti Pardis C. 
Published: August 2020

AbstractRecent outbreaks of viral hemorrhagic fevers (VHFs), including Ebola virus disease (EVD) and Lassa fever (LF), highlight the urgent need for sensitive, deployable tests to diagnose these devastating human diseases. Here we develop CRISPR-Cas13a-based (SHERLOCK) diagnostics targeting Ebola virus (EBOV) and Lassa virus (LASV), with both fluorescent and lateral flow readouts. We demonstrate on laboratory and clinical samples the sensitivity of these assays and the capacity of the SHERLOCK platform to handle virus-specific diagnostic challenges. We perform safety testing to demonstrate the efficacy of our HUDSON protocol in heat-inactivating VHF viruses before SHERLOCK testing, eliminating the need for an extraction. We develop a user-friendly protocol and mobile application (HandLens) to report results, facilitating SHERLOCK’s use in endemic regions. Finally, we successfully deploy our tests in Sierra Leone and Nigeria in response to recent outbreaks.
Development and validation of a sample entropy-based method to identify complex patient-ventilator interactions during mechanical ventilation
Authors: Sarlabous Leonardo , Aquino-Esperanza José , Magrans Rudys , de Haro Candelaria , López-Aguilar Josefina , Subirà Carles , Batlle Montserrat , Rué Montserrat , Gomà Gemma , Ochagavia Ana , Fernández Rafael , Blanch Lluís 
Published: August 2020

AbstractPatient-ventilator asynchronies can be detected by close monitoring of ventilator screens by clinicians or through automated algorithms. However, detecting complex patient-ventilator interactions (CP-VI), consisting of changes in the respiratory rate and/or clusters of asynchronies, is a challenge. Sample Entropy (SE) of airway flow (SE-Flow) and airway pressure (SE-Paw) waveforms obtained from 27 critically ill patients was used to develop and validate an automated algorithm for detecting CP-VI. The algorithm’s performance was compared versus the gold standard (the ventilator’s waveform recordings for CP-VI were scored visually by three experts; Fleiss’ kappa = 0.90 (0.87–0.93)). A repeated holdout cross-validation procedure using the Matthews correlation coefficient (MCC) as a measure of effectiveness was used for optimization of different combinations of SE settings (embedding dimension, m, and tolerance value, r), derived SE features (mean and maximum values), and the thresholds of change (Th) from patient’s own baseline SE value. The most accurate results were obtained using the maximum values of SE-Flow (m = 2, r = 0.2, Th = 25%) and SE-Paw (m = 4, r = 0.2, Th = 30%) which report MCCs of 0.85 (0.78–0.86) and 0.78 (0.78–0.85), and accuracies of 0.93 (0.89–0.93) and 0.89 (0.89–0.93), respectively. This approach promises an improvement in the accurate detection of CP-VI, and future study of their clinical implications.
Comprehensive metabolomic analysis of first-trimester serum identifies biomarkers of early-onset hypertensive disorder of pregnancy
Authors: Kyozuka Hyo , Fukuda Toma , Murata Tsuyoshi , Endo Yuta , Kanno Aya , Yasuda Shun , Yamaguchi Akiko , Ono Miho , Sato Akiko , Hashimoto Koichi , Fujimori Keiya 
Published: August 2020

AbstractHypertensive disorders of pregnancy (HDP) lead to the death of approximately 30,000 women annually, and the identification of biomarkers to predict their onset before symptom occurrence is crucial. Here, we aimed to identify the first-trimester maternal serum biomarkers for predicting early-onset HDP via a comprehensive metabolomic analysis. This study was conducted by the Fukushima Regional Center as an adjunct study to the Japan Environment and Children’s Study. The study comprised 12 patients with early-onset HDP and 12 control subjects with healthy pregnancy whose medical background information was matched with that of the patients by propensity-score matching. Capillary electrophoresis and mass spectrometry-based quantitative analysis of charged metabolites were performed with the first-trimester maternal serum samples. Welch’st-test was used to analyse metabolite peak areas in the two groups. A total of 166 charged metabolites were identified. The peak area of N-dimethylglycine and S-methylcysteine was significantly higher in the first-trimester serum of patients with early-onset HDP than in the controls. Conversely, the peak area of munic acid was significantly decreased in the serum of patients with early-onset HDP. Although we identified potential biomarkers for the prediction and diagnosis of early-onset HDP, no clear marker was identified because of a low statistical power.
2-Nitroimidazoles induce mitochondrial stress and ferroptosis in glioma stem cells residing in a hypoxic niche
Authors: Koike Naoyoshi , Kota Ryuichi , Naito Yoshiko , Hayakawa Noriyo , Matsuura Tomomi , Hishiki Takako , Onishi Nobuyuki , Fukada Junichi , Suematsu Makoto , Shigematsu Naoyuki , Saya Hideyuki , Sampetrean Oltea 
Published: August 2020

AbstractUnder hypoxic conditions, nitroimidazoles can replace oxygen as electron acceptors, thereby enhancing the effects of radiation on malignant cells. These compounds also accumulate in hypoxic cells, where they can act as cytotoxins or imaging agents. However, whether these effects apply to cancer stem cells has not been sufficiently explored. Here we show that the 2-nitroimidazole doranidazole potentiates radiation-induced DNA damage in hypoxic glioma stem cells (GSCs) and confers a significant survival benefit in mice harboring GSC-derived tumors in radiotherapy settings. Furthermore, doranidazole and misonidazole, but not metronidazole, manifested radiation-independent cytotoxicity for hypoxic GSCs that was mediated by ferroptosis induced partially through blockade of mitochondrial complexes I and II and resultant metabolic alterations in oxidative stress responses. Doranidazole also limited the growth of GSC-derived subcutaneous tumors and that of tumors in orthotopic brain slices. Our results thus reveal the theranostic potential of 2-nitroimidazoles as ferroptosis inducers that enable targeting GSCs in their hypoxic niche.
The ancient roots of nicotianamine: diversity, role, regulation and evolution of nicotianamine-like metallophores
Authors: Laffont Clémentine , Arnoux Pascal 
Published: August 2020

AbstractNicotianamine (NA) is a metabolite synthesized by all plants, in which it is involved in the homeostasis of different micronutrients such as iron, nickel or zinc. In some plants it also serves as a precursor of phytosiderophores, which are used for extracellular iron scavenging. Previous studies have also established the presence of NA in filamentous fungi and some mosses, whereas an analogue of NA was inferred in an archaeon. More recently, opine-type metallophores with homology to NA were uncovered in bacteria, especially in human pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa or Yersinia pestis, synthesizing respectively staphylopine, pseudopaline and yersinopine. Here, we review the current state of knowledge regarding the discovery, biosynthesis, function and regulation of these metallophores. We also discuss the genomic environment of the cntL gene, which is homologous to the plant NA synthase (NAS) gene, and plays a central role in the synthesis of NA-like metallophores. This reveals a large diversity of biosynthetic, export and import pathways. Using sequence similarity networks, we uncovered that these metallophores are widespread in numerous bacteria thriving in very different environments, such as those living at the host–pathogen interface, but also in the soil. We additionally established a phylogeny of the NAS/cntL gene and, as a result, we propose that this gene is an ancient gene and NA, or its derivatives, is an ancient metallophore that played a prominent role in metal acquisition or metal resistance. Indeed, our phylogenetic analysis suggests an evolutionary model where the possibility to synthesize this metallophore was present early in the appearance of life, although it was later lost by most living microorganisms, unless facing metal starvation such as at the host–pathogen interface or in some soils. According to our model, NA then re-emerged as a central metabolite for metal homeostasis in fungi, mosses and all known higher plants.
Verhaltenssüchte in der ICD-11
Authors: Rumpf Hans-Jürgen , Brandt Dominique 
Published: August 2020

Zusammenfassung
Ziel Der Beitrag stellt die Verortung von Verhaltenssüchten in
der ICD-11 dar und gibt einen Ausblick auf die zukünftige
Entwicklung.
Methodik Sichtung der Literatur
Ergebnisse Auf Basis von Expertenmeetings der Weltgesundheitsorganisation
(WHO) wurde ein Vorschlag entwickelt, auf Basis dessen die Gambling und Gaming
Disorder in die aktuelle Fassung der International Classification of Diseases
(ICD-11) aufgenommen wurden. Beide Störungen werden mit den gleichen 3
Kernmerkmalen beschrieben (Kontrollverlust, Priorität im Leben und
Fortsetzung trotz negativer Konsequenzen) und erfordern darüber hinaus
das Vorliegen einer funktionalen Beeinträchtigung. Eine Reihe von
Studien belegt die klinische Relevanz dieser Entscheidung. Darüber
hinaus lassen sich weitere spezifizierte Verhaltenssüchte kodieren,
wobei nach Sichtung der Literatur insbesondere Buying-Shopping Disorder,
Pornografy Use Disorder und Social Networks Use Disorder hierfür
geeignet erscheinen.
Schlussfolgerung Insbesondere bei der Computerspielstörung ist zu
erwarten, dass die Aufnahme in die ICD-11 die Entwicklung von Diagnostik,
Prävention und Therapie diese Störung fördert. Unter
Federführung der WHO werden derzeit diagnostische Verfahren für
beide Störungen entwickelt, um Standardinstrumente bereit zu
stellen.