bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR/Cas9‐mediated whole genomic wide knockout screening identifies mitochondrial ribosomal proteins involving in oxygen‐glucose deprivation/reperfusion resistance
Authors: Guan Xinjie , Zhang Hainan , Qin Haiyun , Chen Chunli , Hu Zhiping , Tan Jieqiong , Zeng Liuwang 
Published: July 2020

AbstractRecanalization therapy by intravenous thrombolysis or endovascular therapy is critical for the treatment of cerebral infarction. However, the recanalization treatment will also exacerbate acute brain injury and even severely threatens human life due to the reperfusion injury. So far, the underlying mechanisms for cerebral ischaemia‐reperfusion injury are poorly understood and effective therapeutic interventions are yet to be discovered. Therefore, in the research, we subjected SK‐N‐BE(2) cells to oxygen‐glucose deprivation/reperfusion (OGDR) insult and performed a pooled genome‐wide CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR‐associated protein 9) knockout screen to discover new potential therapeutic targets for cerebral ischaemia‐reperfusion injury. We used Metascape to identify candidate genes which might involve in OGDR resistance. We found that the genes contributed to OGDR resistance were primarily involved in neutrophil degranulation, mitochondrial translation, and regulation of cysteine‐type endopeptidase activity involved in apoptotic process and response to oxidative stress. We then knocked down some of the identified candidate genes individually. We demonstrated that MRPL19, MRPL32, MRPL52 and MRPL51 inhibition increased cell viability and attenuated OGDR‐induced apoptosis. We also demonstrated that OGDR down‐regulated the expression of MRPL19 and MRPL51 protein. Taken together, our data suggest that genome‐scale screening with Cas9 is a reliable tool to analyse the cellular systems that respond to OGDR injury. MRPL19 and MRPL51 contribute to OGDR resistance and are supposed to be promising targets for the treatment of cerebral ischaemia‐reperfusion damage.
Diagnostic and therapeutic potential of exosomes in Alzheimer’s disease
Authors: Soares Martins Tânia , Trindade Dário , Vaz Margarida , Campelo Inês , Almeida Martim , Trigo Guilherme , da Cruz e Silva Odete A. B. , Henriques Ana Gabriela 
Published: July 2020

AbstractExosomes are small extracellular vesicles released by almost all cell types in physiological and pathological conditions. The exosomal potential to unravel disease mechanisms, or to be used as a source of biomarkers, is being explored, in particularly in the field of neurodegenerative diseases. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world and exosomes appear to have a relevant role in disease pathogenesis. This review summarizes the current knowledge on exosome contributions to AD as well as their use as disease biomarker resources or therapeutic targets. The most recent findings with respect to both protein and miRNA biomarker candidates for AD, herein described, highlight the state of the art in this field and encourage the use of exosomes derived from biofluids in clinical practice in the near future.
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Only some attempts at meaning making are successful: The role of change‐relatedness and positive implications for the self
Authors: Huang Manxia , Schmiedek Florian , Habermas Tilmann 
Published: July 2020

AbstractObjectiveAlthough meaning making and specifically autobiographical reasoning are expected to relate to well‐being, findings tend to be mixed. Attempts at meaning making do not always lead to meaning made. We aimed to disentangle these complex relationships and also explore the role of level of education.MethodNinety participants (mean age 36.73 years,SD = 7.27; 74.4% women, 25.6% men) who had experienced the loss of a parent through death, going missing, or Alzheimer's disease narrated this loss, a sad, a turning point, and a self‐defining memory, and completed questionnaires assessing depression, trauma symptoms, and protracted grief. Three aspects of autobiographical reasoning (quantity, valence, and change‐relatedness of self‐event connections) were related to meaning made (sophistication of meaning making) and symptom level.ResultsYears of education correlated both with positive implications of autobiographical reasoning and with meaning made. The quantity, positivity, and change‐relatedness of attempts at meaning making (self‐event connections) predicted accomplished meaning made, and positivity alone predicted less prolonged grief.ConclusionsAdapting the life story after a loss such that change of the self is acknowledged and positive change can be constructed helps finding meaning and lowering protracted grief. These changes in narrative identity are supported by more years of education.
Sleep disturbances and disability following work‐related injury and illness: Examining longitudinal relationships across three follow‐up waves
Authors: Fan Jonathan K. , Sim Malcolm , Lilley Rebbecca , Wong Imelda S. , Smith Peter M. 
Published: July 2020

SummaryDespite the high burden of sleep disturbances among the general population, there is limited information on prevalence and impact of poor sleep among injured workers. This study: (a) estimated the prevalence of sleep disturbance following work‐related injury; and (b) examined the longitudinal association between sleep disturbances and disability/functioning, accounting for reciprocal relationships and mental illness. Longitudinal survey data were collected from workers' compensation claimants with a time‐loss claim in Victoria, Australia (N = 700). Surveys were conducted at baseline, 6 months and 12 months. Sleep disturbance was measured using the Patient‐Reported Outcomes Measurement Information System (PROMIS) questionnaire. Disability/functioning was based on self‐reported activity limitations, participation restrictions and emotional functioning. Path models examined the association between disability/functioning and sleep. Mean sleep disturbance T‐scores were 55.2 (SD 11.4) at 6 months, with 36.4% of the sample having a T‐score of 60+. Longitudinal relationships were observed between disability (specifically, emotional functioning) and sleep disturbances across successive follow‐up waves. For example, each unit increase in T2 emotional functioning (five‐point scale) was associated with a 1.1 unit increase in T3 sleep disturbance (approximately 29–76 scale). Cross‐lagged path models found evidence of a reciprocal relationship between disability and sleep, although adjustment for mental illness attenuated the estimates to the null. In conclusion, sleep disturbances are common among workers' compensation claimants with work injuries/illnesses. Given the links between some dimensions of disability, mental health and sleep disturbances, the findings have implications for the development of interventions that target the high prevalence of sleep problems among working populations.
Normal utilization rate in the Sraffa framework
Authors: Huang Biao 
Published: July 2020

AbstractThis paper deals with the normal utilization rate in the Sraffa framework. It further presents two arguments about the utilization controversy surrounding the neo‐Kaleckian theory of growth and distribution: First, it shows that the normal utilization rate is generally not independent of demand and the growth rate, and this result does not rely on the neo‐classical production function and other restrictive assumptions. Second, it argues that endogenizing the normal utilization rate is not a general solution for the utilization controversy.
Visualising virulence factors: Trichophyton benhamiaes subtilisins demonstrated in a guinea pig skin ex vivo model
Authors: Baumbach Christina‐Marie , Michler Jule Kristin , Nenoff Pietro , Uhrlaß Silke , Schrödl Wieland 
Published: July 2020

AbstractBackgroundDermatophytoses rank among the most frequent communicable diseases in humans, and the zoonotic transmission is increasing. The zoophilic dermatophyte Trichophyton (T.) benhamiae is nowadays one of the main causes of tinea faciei et corporis in children. However, scientific data on molecular pathomechanisms and specific virulence factors enabling this ubiquitous occurrence are scarce.ObjectivesTo study tissue invasion and the expression of important virulence factors of T. benhamiae, isolates that were recovered from two groups of hosts (humans vs. guinea pigs (GP)) using an ex vivo skin model.MethodsAfter confirmation of species identity by ITS sequencing, CFU suspensions of dermatophyte isolates (n = 20) were applied to the skin infection model and cultured. Employing specific immunofluorescence staining techniques, the expression of subtilisin 3 and 6 and metallocarboxypeptidase A was analysed. The general mode of invasion was explored. Results were compared with biopsies of naturally infected GP.ResultsAll isolates were successfully recovered and proliferated well after application to the infection model. Progressive invasion of hyphae through all skin structures and destruction of explants were observed with early events being comparable to natural infection. An increasing expression of the examined virulence factors towards the end of culture was noticed but no difference between the two groups of isolates.ConclusionsFor the first time, important in vivo markers of dermatophytosis were visualised immunohistochemically in an ex vivo skin infection model and in skin biopsies of GP naturally infected with T. benhamiae. More research on the underlying pathomechanisms of dermatophyte infection is urgently needed.
Antidermatophytic activity of synthetic peptides: Action mechanisms and clinical application as adjuvants to enhance the activity and decrease the toxicity of Griseofulvin
Authors: Souza Pedro F. N. , Lima Patrícia G. , Freitas Cleverson D. T. , Sousa Daniele O. B. , Neto Nilton A. S. , Dias Lucas P. , Vasconcelos Ilka M. , Freitas Larissa B. N. , Silva Rafael G. G. , Sousa Jeanlex S. , Silva Ayrles F. B. , Oliveira Jose T. A. 
Published: July 2020

AbstractBackgroundDermatophytes belonging to the Trichophyton genus are important human pathogens, but they have developed resistance to griseofulvin, the most common antifungal drug used to treat dermatophytosis.ObjectiveThis study was aimed to evaluate the antidermatophytic activity of synthetic peptides, as well as mechanisms of action and synergistic effect with griseofulvin.MethodsScanning electron microscopy (SEM), atomic force microscopy (AFM) and fluorescence microscopy (FM) were employed to understand the activity and the mechanism of action of peptides.ResultsHere we report that synthetic peptides at 50 μg/mL, a concentration 20‐fold lower than griseofulvin, reduced the microconidia viability of T. mentagrophytes and T. rubrum by 100%, whereas griseofulvin decreased their viability by only 50% and 0%, respectively. The action mechanism of peptides involved cell wall damage, membrane pore formation and loss of cytoplasmic content. Peptides also induced overproduction of reactive oxygen species (ROS) and enhanced the activity of griseofulvin 10‐fold against both fungi, suggesting synergistic effects, and eliminated the toxicity of this drug to human erythrocytes. Docking analysis revealed ionic and hydrophobic interactions between peptides and griseofulvin, which may explain the decline of griseofulvin toxicity when mixed with peptides.ConclusionTherefore, our results strongly suggest six peptides with high potential to be employed alone as new drugs or as adjuvants to enhance the activity and decrease the toxicity of griseofulvin.
Endothelin‐1 in the pathophysiology of obesity and insulin resistance
Authors: Jenkins Haley N. , Rivera‐Gonzalez Osvaldo , Gibert Yann , Speed Joshua S. 
Published: July 2020

SummaryThe association between plasma endothelin‐1 (ET‐1) and obesity has been documented for decades, yet the contribution of ET‐1 to risk factors associated with obesity is not fully understood. In 1994, one of first papers to document this association also noted a positive correlation between plasma insulin and ET‐1, suggesting a potential contribution of ET‐1 to the development of insulin resistance. Both endogenous receptors for ET‐1, ETA and ETB are present in all insulin‐sensitive tissues including adipose, liver and muscle, and ET‐1 actions within these tissues suggest that ET‐1 may be playing a role in the pathogenesis of insulin resistance. Further, antagonists for ET‐1 receptors are clinically approved making these sites attractive therapeutic targets. This review focuses on known mechanisms through which ET‐1 affects plasma lipid profiles and insulin signalling in these metabolically important tissues and also identifies gaps in our understanding of ET‐1 in obesity‐related pathophysiology.
Preparing for sperm‐targeted contraception: College students’ perceptions and intentions related to non‐hormonal intravas injectable gel
Authors: Buck Kirstin A. , Stadick Jessica L. , Frazier Marian L. 
Published: July 2020

AbstractObjectiveThe objective of the study was to evaluate college students’ perceptions and behavioral intentions related to a new long‐acting reversible contraceptive (LARC) for people with penises: non‐hormonal intravas injectable gel (NH‐IVIG).Design and SampleData collection utilized predictive constructs from the theory of planned behavior. An online questionnaire surveyed undergraduates (ages 18–24 years) at a Midwestern, liberal arts college (N = 460).ResultsOf potential NH‐IVIG users, 28.6% of males and 51.4% of females reported being overall likely to use or encourage its usage. The top three hypothetical NH‐IVIG promoters were low cost, reversibility, and infrequent administration. High cost, new product uncertainties, plus administration via injection for the males, were the most frequently cited NH‐IVIG deterrents. A majority of potential users indicated intentions to use protective barriers or other contraceptives simultaneously with NH‐IVIG; females were more likely overall. Most respondents (males, 90.4%; females, 98.5%) agreed all sexual partners should be equally responsible for contraception. Over half trusted both males and females to use contraception, but females were significantly more trusted and trusting.ConclusionUnderstanding factors influencing NH‐IVIG usage can direct initiatives for sperm‐targeted LARCs to mitigate risk behaviors and optimize public health promotion.
From Accountants to Detectives: How Nuclear Safeguards Inspectors Make Knowledge at the International Atomic Energy Agency
Authors: Weichselbraun Anna 
Published: July 2020

AbstractThe International Atomic Energy Agency (IAEA) verifies state compliance with the Nuclear Nonproliferation Treaty through nuclear safeguards. The agency's legitimacy derives from the convincing display of technical authority. The politics of nuclear things, however, constantly threaten to undermine this authority. Nuclear safeguards are made legibly authoritative and credibly technical through bureaucratic objectivity. This epistemic logic and practice is widely shared by projects of technocratic governance in the liberal international order. After the discovery of Iraq's secret nuclear weapons program, the IAEA transformed its accounting‐based knowledge practices. However, these transformations into more detective‐like ways of knowing call into question the presumed technical purity of safeguards reports. This article unearths the historical origins of safeguards as bureaucratically objective knowledge and demonstrates its enduring legacy at the IAEA, as its bureaucrats and diplomats attempt to manage the tension between effectiveness and credibility.
Improving and standardizing protocols for alkaline protease quantification in fish
Authors: Nolasco‐Soria Héctor 
Published: July 2020

AbstractAssessing the activity of alkaline protease is a common procedure in many biological, physiological and nutritional studies, including the maturation and digestive capacity of the digestive tract, in gastric and non‐gastric fish species. After reviewing the available literature on fish digestive alkaline proteases published during a time span of ten years (2008–2018), it has been detected some possible methodological and/or interpretative inconsistencies in this kind of studies when quantifying alkaline protease activity and concluded that special attention should be paid on: (i) the proper preparation of intestine and pyloric caeca extracts, (ii) the use of the proper reaction conditions at the normal range of physiological pH values and temperature and (iii) the proper quantification of the number of peptide bonds hydrolysed for alkaline protease unit calculation. The implementation of these recommendations and the proposal of more suitable (previously tested) methodological steps will promote the standardization of feasible alkaline protease analytical procedures, as well as improve the reliability of comparative studies between different fish species of aquacultural importance, dealing with the alkaline proteolytic enzymes.
Is backing grounding?
Authors: Sjölin Wirling Ylwa 
Published: July 2020

AbstractSeparatists are grounding theorists who hold that grounding relations and metaphysical explanations are distinct, yet intimately connected in the sense that grounding relations back metaphysical explanations, just as causal relations back causal explanations. But Separatists have not elaborated on the nature of the ‘backing’ relation. In this paper, I argue that backing is a form of (partial) grounding. In particular, backing has many of the properties commonly attributed to grounding, and taking backing to be partial grounding allows Separatists to make the most of their position vis‐à‐vis their Unionist opponents.
Births and the City: Urban Cycles and Increasing Socio‐Spatial Heterogeneity in a Low‐Fertility Context
Authors: Salvati Luca 
Published: July 2020

AbstractAnalysis of fertility trends along urban gradients contributes to assess socio‐demographic change at larger scales and the new geography of metropolitan growth at smaller scales. At larger scales, urban fertility was systematically lower than rural fertility; at smaller scales, suburbs were found to have higher fertility than central districts and the neighbouring rural areas. However, fertility divides have rarely been re‐contextualised in a long‐term perspective, considering the influence of exogenous factors that change over time with urban cycles. Assuming that spatial fertility variations are contextual to the development stage of a given region, the present study goes beyond the traditional ‘urban‐suburban‐rural’ divide and provides a long‐term vision that integrates small‐scale fertility variations and city life cycles. The study investigates spatial trends in a fertility index along a cycle from urbanisation to re‐urbanisation in a low‐fertility European context (Athens, Greece) using a multi‐scale analysis framework. The empirical findings of this study demonstrate that rural fertility was systematically lower than urban fertility apart from a short time interval (1950s). Fertility in urban locations was the highest during earlier stages of urbanisation. In suburban locations, fertility increased during late suburbanisation, stabilising (or declining slightly) with counter‐urbanisation. Re‐urbanisation was associated with a greater spatial heterogeneity in fertility rates. By documenting a differential response of fertility to urban cycles, our study re‐frames the relationship between natural population dynamics and metropolitan transitions, concluding that regional fertility divides are temporary outcomes of a specific ensemble of socio‐economic forces underlying a given urban model.
Severe COVID‐19 in a patient with chronic graft‐versus‐host disease after hematopoietic stem cell transplant successfully treated with ruxolitinib
Authors: Saraceni Francesco , Scortechini Ilaria , Mancini Giorgia , Mariani Marianna , Federici Irene , Gaetani Mariana , Barbatelli Paolo , Minnucci Maria Luisa , Bagnarelli Patrizia , Olivieri Attilio 
Published: July 2020

AbstractGraft‐versus‐host disease (GVHD) is a common complication of hematopoietic stem cell transplant, which is known to be mediated by cytotoxic T‐cell effectors and dysregulated inflammatory cytokines. Similarly, the lung injury observed in severe COVID‐19 cases appears to be related to a massive production of pro‐inflammatory cytokines. The selective JAK1/2 inhibitor ruxolitinib has shown promising results in the context of GVHD, and different trials are currently underway in patients with severe COVID‐19; nevertheless, no clinical observation of safety or efficacy of treatment with ruxolitinib in this context has been published yet. We describe a first case of severe COVID‐19 developed after hematopoietic stem cell transplantation in a patient with a concomitant chronic GVHD (cGVHD), in which a treatment with ruxolitinib was administered with good tolerance and positive outcome.
Characteristics and serological patterns of COVID‐19 convalescent plasma donors: optimal donors and timing of donation
Authors: Li Ling , Tong Xunliang , Chen Hanwei , He Rui , Lv Qilu , Yang Ru , Zhao Lei , Wang Jue , Xu Haixia , Liu Chuanqiao , Chen Guoan , Chen Sitian , Li Chenyue , Qiao Jiajia , Yang Juntao , Wu Yanyun , Liu Zhong 
Published: July 2020

BACKGROUNDThe lack of effective treatments against the 2019 coronavirus disease (COVID‐19) has led to the exploratory use of convalescent plasma for treating COVID‐19. Case reports and case series have shown encouraging results. This study investigated SARS‐CoV‐2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection.METHODSRecovered COVID‐19 patients, aged 18‐55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS‐CoV‐2 N‐specific IgM, IgG, and S‐RBD‐specific IgG levels were measured by enzyme‐linked immunosorbent assay (ELISA).RESULTSWhereas levels of N‐specific IgM antibody declined after recovery, S‐RBD‐specific and N‐specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5°C or lasting longer than 3 days exhibited higher levels of S‐RBD‐specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S‐RBD‐specific IgG titer of ≥1:160 and 78% had a titer of ≥1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C, 100% had an S‐RBD‐specific IgG titer of ≥1:160 and 93% had a titer of ≥1:640.CONCLUSIONThis study indicates that the S‐RBD‐specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID‐19 symptoms. We recommend the following selection criteria for optimal donation of COVID‐19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S‐RBD‐specific IgG titers.