bluuebunny/crossref_metadata_2025 huggingface dataset:
Adolescent social withdrawal, parental psychological control, and parental knowledge across seven years: A developmental cascade model
Authors: Lin Hua , Harrist Amanda W. , Lansford Jennifer E. , Pettit Gregory S. , Bates John E. , Dodge Kenneth A.
Published: May 2020

Introduction

Social withdrawal can be problematic for adolescents, increasing the risk of poor self‐efficacy, self‐esteem, and academic achievement, and increased levels of depression and anxiety. This prospective study follows students across adolescence, investigating links between social withdrawal and two types of parenting hypothesized to impact or be reactive to changes in social withdrawal.

Methods

Adolescent social withdrawal and parenting were assessed across seven years in a U.S. sample, beginning when students were in 6th grade and ending in 12th grade. The sample consisted of 534 adolescents (260 girls and 274 boys, 82% Euro‐ and 16% African‐American). Social withdrawal was assessed in four grades using at least two informants (teachers, mothers, and/or adolescents). Mothers' and fathers' psychological control and monitoring‐related knowledge were assessed by adolescents at two time points. A developmental cascade analysis was conducted using structural equation modeling to assess how withdrawal and control‐related parenting impact each other transactionally over time. Analyses included a test for gender differences in the model.

Results

The cascade model revealed that, controlling for previous levels of social withdrawal and parenting, earlier social withdrawal positively predicted psychological control and negatively predicted monitoring knowledge, and earlier parental psychological control—but not monitoring knowledge—predicted later social withdrawal. No adolescent gender differences were identified in the associations between social withdrawal and parental knowledge.

Conclusions

This study offers insight into the mechanisms by which adolescents become more or less withdrawn over time, and suggests psychological control as a point of psychoeducation or intervention for parents.
AI Customer Service: Task Complexity, Problem-Solving Ability, and Usage Intention
Authors: Xu Yingzi , Shieh Chih-Hui , van Esch Patrick , Ling I-Ling
Published: May 2020

Artificial intelligence (AI) in the context of customer service, we define as a technology-enabled system for evaluating real-time service scenarios using data collected from digital and/or physical sources in order to provide personalised recommendations, alternatives, and solutions to customers’ enquiries or problems, even very complex ones. We examined, in a banking services context, whether consumers preferred AI or Human online customer service applications using an experimental design across three field-based experiments. The results show that, in the case of low-complexity tasks, consumers considered the problem-solving ability of AI to be greater than that of human customer service and were more likely to use AI while, conversely, for high-complexity tasks, they viewed human customer service as superior and were more likely to use it than AI. Moreover, we found that perceived problem-solving ability mediated the effects of customers’ service usage intentions (i.e., their preference for AI vs. Human) with task complexity serving as a boundary condition. Here we discuss our research and the results and conclude by offering practical suggestions for banks seeking to reach customers and engage with them more effectively by leveraging the distinctive features of AI customer service.
Low-dose fractionated radiation with induction docetaxel and cisplatin followed by concurrent cisplatin and radiation therapy in locally advanced nasopharyngeal cancer
Authors: Al-Rajhi Nasser M. , Khalil Ehab M. , Ahmad Shoaib , Soudy Hussein , AlGhazi Mohammad , Fatani Doha M. , Memon Muhammed , Abouzied Moheieldin , Khafaga Yasser M.
Published: May 2020

Objective/Background:

To evaluate the efficacy and outcome of adding low-dose fractionated radiotherapy (LDFRT) to induction chemotherapy plus concurrent chemoradiation in locally advanced nasopharyngeal carcinoma (LANPC).

Methods:

A single-institute, phase II–III, prospectively controlled randomized clinical trial was performed at King Faisal Specialist Hospital and Research Centre. Patients aged 18–70 years with WHO type II and III, stage III–IVB nasopharyngeal carcinoma, Eastern Cooperative Oncology Group performance score of 0–2, with adequate hematological, renal, and hepatic function were eligible. In total, 108 patients were enrolled in this trial. All patients received two cycles of induction docetaxel and cisplatin (75 mg/m2 each) chemotherapy on Days 1 and 22, followed by concurrent chemoradiation therapy. Radiation therapy consisted of 70 Gy in 33 fractions, with concurrent cisplatin 25 mg/m2 for 4 days on Days 43 and 64. Patients were randomly assigned to either adding LDFRT (0.5 Gy twice daily 6 hours apart for 2 days) to induction chemotherapy in the experimental arm (54 patients) or induction chemotherapy alone in the control arm (54 patients).

Results:

There was no significant difference in the post-induction response rates (RRs) or in toxicity between the two treatment arms. The 3-year overall survival (OS), locoregional control (LRC), and distant metastases-free survival (DMFS) rates for experimental arm and control arm were 94% versus 93% (p = .8), 84.8% versus 87.5% (p = .58), and 84.1% versus 91.6% (p = .25), respectively.

Conclusion:

The results showed no benefit from adding LDFRT to induction chemotherapy in terms of RR, OS, LRC, and DMFS.
Noninfectious neurologic complications of hematopoietic cell transplantation
Authors: Sheikh Mohammad Abdurrehman , Toledano Michel , Ahmed Sairah , Gul Zartash , Hashmi Shahrukh K.
Published: May 2020

Objective/Background:

Neurological complications occur at a high frequency after hematopoietic cell transplantation (HCT). However, an absence is noted in the published literature as regards the quantification of the exact burden and the outcomes thereof. In this systematic review, we endeavored to detail if the recipients of HCT developed any noninfectious neurological events/complications.

Methods:

According to the PICO criteria, medical literature was searched. Complications that were evaluated included: stroke, peripheral neuropathy, myasthenia gravis, seizures, and posterior reversible encephalopathy syndrome. After strictly defining relevant variables and parameters, data from 173 eligible articles were then extracted accordingly, from the full text for each, for quantitative analysis; additionally, two American Society of Hematology conference abstracts were also subject to data extraction.

Results:

As is evident from the results of the data analysis, an increased frequency of these complications was seen in the HCT recipient population in comparison to the general population. The relative risk ranged from 1.33× to 142× depending on the complication studied.

Conclusion:

These findings demonstrate that the recipients of HCT had a significantly higher risk of neurological complications and that their early recognition can enhance the monitoring of HCT survivors for the early developmental signs of neurological toxicity. This would facilitate timely interventions, thus ensuring a better quality of life.
Hazard control for communicable disease transport at Ornge
Authors: Peddle Michael B. , Smith Justin A.
Published: May 2020

Transporting patients with communicable diseases is common in critical care transport operations. At Ornge, Ontario's critical care transport provider, 13.7% of patients required contact, droplet, or airborne precautions during transport in 2019–2020. Ensuring that staff are protected while transporting patients with communicable diseases must remain a prime directive for medical transport administrators and operators. Success in safety requires a robust system of hazard identification and adherence to generally accepted methods of hazard control. This commentary will discuss some of the administrative and engineering controls, as well as the personal protective equipment (PPE) strategies deployed at Ornge.
Lockdown in a specialised rehabilitation unit: the best of times
Authors: Glancy D. , Reilly L. , Cobbe C. , Glynn M. , Punchoo S. , Foy K.
Published: May 2020

Specialised rehabilitation units offer inpatient multi-disciplinary rehabilitation for individuals with severe and enduring mental illness. A cornerstone of therapy is the work in the community through further education and community organisations. However, coronavirus restrictions have meant that such external supports are no longer available for the duration of the crisis. This has led to opportunities for developing new ways of offering rehabilitation within hospital environments. This article describes some of the new initiatives developed. The benefits of the lockdown for service users are also discussed. Many found the cessation of visits from family members with whom they had an ambivalent relationship helpful. The lockdown improved relationships between patients on the unit and encouraged a greater feeling of community. The lockdown has also emphasised the importance of team self-awareness and an awareness of the nature of the treatments offered.
The challenges of COVID-19 for community pharmacists and opportunities for the future
Authors: Hayden John C. , Parkin Rebecca
Published: May 2020

Pharmacists, like psychiatrists, have modified their practices amidst COVID-19 in order to guarantee care and support to their patients. Designated an essential frontline service, community pharmacists are facing a spectrum of challenges to surmount to ensure patient care continues. These include assisting in the prevention of infection, managing supply chains, preventing stockpiling and provision of evidence-based medical information. However, disasters like COVID-19 disproportionately affect poor and vulnerable populations, and patients with mental health conditions may be among the hardest hit. Pharmacist-level, system-level and regulatory responses have sought to minimise this impact, although there is likely to be a lasting impression on the profession, both good and bad. This article reviews the pandemic-related challenges and responses by pharmacists, as well as forming recommendation for areas of professional support and role expansion, particularly in the case of mental health.
Covid-19, child and adolescent mental health – Croatian (in)experience
Authors: Franic Tomislav , Dodig-Curkovic Katarina
Published: May 2020

The Covid-19 pandemic has caused unseen socio-economic changes all over the world, where enormous efforts are being made to preserve lives and maintain functional health systems. A secondary concern is to mitigate the severe economic consequences of the crisis. Different approaches have been adopted with varying outcomes and experiences. But regardless of the different approaches taken, one thing is common for all societies during this pandemic: fear and anxiety. This fear extends from concerns about the present situation, for the health and well-being of family members and loved ones from Covid-19 infection, to fears relating to how long the crisis will last, to the potential economic consequences of the pandemic (perhaps not seen in our lifetimes) and the ultimate fear of future uncertainty. Across the world, health systems are being faced with unprecedented challenges. At their core, these challenges are the same: how to beat Covid-19. Certainly, there are differences in how individual systems are organized and how they address the main issues arising from the pandemic while not forgetting the ongoing healthcare needs of the general population. In this paper, we share some perspectives from Croatia regarding Child and Adolescent Mental Health services (CAMHs) in these extraordinary circumstances. We give our personal insights on deficiencies in Child and Adolescent Mental Health Services prior to the arrival of Covid-19, which have contributed to difficulties in mitigating and managing the ongoing crisis.
Forensic psychiatry and Covid-19: accelerating transformation in forensic psychiatry
Authors: Kennedy H. G. , Mohan D. , Davoren M.
Published: May 2020

Swift medically led scientifically informed responses to the Covid-19 epidemic nationally have been demonstrably superior to other, non-scientific approaches. In forensic psychiatry and across all psychiatric services, urgent and clinically led responses have underlined redundancies and confusions in the governance of mental health services and a vacuum in policy makers. For the future, a greater emphasis on services for patients with schizophrenia and other severe, enduring mental disorders must aim at reducing standardised mortality ratios, managing risk of violence and improving hard outcomes such as symptomatic remission, functional recovery and forensic recovery of autonomy. This will require more use of information technology at service level and at national level where Scandinavian-style population-based data linkage research must now become legally sanctioned and necessary. A national research and development centre for medical excellence in forensic psychiatry is urgently required and is complimentary to and different from quality management.
RELIGION AND POLITICS IN AFRICA: THREE STUDIES ON NIGERIA
Authors: Salau Mohammed Bashir
Published: May 2020

Until the second half of the twentieth century, the role of religion in Africa was profoundly neglected. There were no university centers devoted to the study of religion in Africa; there was only a handful of scholars who focused primarily on religious studies and most of them were not historians; and there were relatively few serious empirical studies on Christianity, Islam, and African traditional religions. This paucity of rigorous research began to be remedied in the 1960s and by the last decade of the twentieth century, the body of literature on religion in Africa had expanded significantly. The burgeoning research and serious coverage of the role of religion in African societies has initially drawn great impetus from university centers located in the West and in various parts of Africa that were committed to demonstrating that Africa has a rich history even before European contact. Accordingly scholars associated with such university centers have since the 1960s acquired and systematically catalogued private religious manuscripts and written numerous pan-African, regional, national, and local studies on diverse topics including spirit mediumship, witchcraft, African systems of thought, African evangelists and catechists, Mahdism, Pentecostalism, slavery, conversion, African religious diasporas and their impact on host societies, and religion and politics. Although the three works under review here deal with the role of religion in an African context, they mainly contribute to addressing three major questions in the study of religion and politics: How do Islam and other religious orientations shape public support for democracy? What is the primary cause of conflict or religious violence? What strategies should be employed to resolve such conflicts and violence?
Agenda Seeding: How 1960s Black Protests Moved Elites, Public Opinion and Voting
Authors: WASOW OMAR
Published: May 2020

How do stigmatized minorities advance agendas when confronted with hostile majorities? Elite theories of influence posit marginal groups exert little power. I propose the concept of agenda seeding to describe how activists use methods like disruption to capture the attention of media and overcome political asymmetries. Further, I hypothesize protest tactics influence how news organizations frame demands. Evaluating black-led protests between 1960 and 1972, I find nonviolent activism, particularly when met with state or vigilante repression, drove media coverage, framing, congressional speech, and public opinion on civil rights. Counties proximate to nonviolent protests saw presidential Democratic vote share increase 1.6–2.5%. Protester-initiated violence, by contrast, helped move news agendas, frames, elite discourse, and public concern toward “social control.” In 1968, using rainfall as an instrument, I find violent protests likely caused a 1.5–7.9% shift among whites toward Republicans and tipped the election. Elites may dominate political communication but hold no monopoly.
The Role and Regulation of Child Factory Labour During the Industrial Revolution in Australia, 1873–1885
Authors: Johnston Madeleine
Published: May 2020

This study investigates child factory labour in Victoria, the most populous and industrialized colony in Australia in the second half of the nineteenth century. Three sources of primary data are analysed: Royal Commission reports, texts of bills and statutes, and parliamentary and public debates. The findings inform current academic debates by enhancing understanding of the role played by child workers during industrialization. They show that children were low-cost substitutes for adult males and that child labour was central to ongoing industrialization. A wide range of industries and jobs is identified in which children were employed in harsh conditions, in some instances in greater proportions than adults. Following the reports of the Royal Commission, the parliament of Victoria recognized a child labour problem serious enough to warrant regulation. While noting that circumstances were not as severe as in Britain, it passed legislation in 1885 with provisions that offered more protection to children than those in the British factory act of 1878. The legislation also offered more protection than factory laws in other industrializing colonies and countries. The findings throw light on the character of colonial liberal reformers in a wealthy colony who sought to create a better life for white settlers by adopting policies of state intervention.
Power in relations of international organisations: The productive effects of ‘good’ governance norms in global health
Authors: Pantzerhielm Laura , Holzscheiter Anna , Bahr Thurid
Published: May 2020

In recent years, scholarship on international organisations (IO) has devoted increasing attention to the relations in which IOs are embedded. In this article, we argue that the rationalist-institutionalist core of this scholarship has been marked by agentic, repressive understandings of power and we propose an alternative approach to power as productive in and of relations among IOs. To study productive power in IO relations, we develop a theoretical framework centred on the concept of ‘metagovernance norms’ as perceptions about the proper ‘governance of governance’ that are shared among IOs in a governance field. Drawing on discourse theory, we contend that metagovernance norms unfold productive power effects, as dominant notions of how to govern well and effectively (i) fix meanings, excluding alternative understandings and (ii) are inscribed into practices and institutions, hence reshaping inter-organisational relations over time. To illustrate our framework, we trace metagovernance norms in discourses among health IOs since the 1990s. We find a historical transformation from beliefs in the virtues of partnerships, pluralisation, and innovation, towards discursive articulations that emphasise harmonisation, order, and alignment. Moreover, we expose the productive power of metagovernance norms by showing how they were enacted through practices and institutions in the global health field.
The Expiration of Commitments in Adelaide Procter's “Homeward Bound”
Authors: Harrington Emily
Published: May 2020

It has been a long time since the poetry of Adelaide Anne Procter, a favorite of Queen Victoria, captured much interest from readers of poetry, whether they be anthology aficionados, scholars, or students. Now considered a minor poet of the period, she was nevertheless a quintessential poet activist of her day, raising money for and working with the Providence Row Night Refuge, editing and contributing to the English Women's Journal alongside the Langham Place Feminists and the Society for the Employment of Women. She published volumes of her own poems, one of which ran to as many as nineteen editions between 1858 and 1881, and her work was featured regularly in Charles Dickens's periodical Household Words. Her legacy stands as a powerful testimony to the way ideas and tastes change over time. Full of angels, Christmases, quietly suffering children, and pious nuns (she converted to Catholicism in 1851), her poetry is often dismissed as sentimental and clichéd. A glance at her forms reveals many straightforward tetrameters with expected alternating, end-stopped rhymes, an easiness that seems to ally form and content. If Adorno had ever taken the time to read her poetry, he probably would have hated it, not just for its Catholic faith and its frequent focus on sin and redemption, but for its attempt “to work at the level of fundamental attitudes,” typical of committed art. Consider these lines from her frequently anthologized “Homeless,” which asks readers to recognize that their society takes better care of animals, criminals, and commodities than of the homeless poor:

For each man knows the market value

Of silk or woolen or cotton…

But in counting the riches of England

I think our Poor are forgotten.
Fear of Commitment
Authors: Lavery Grace Elisabeth
Published: May 2020

What does it mean to commit? And why are men stereotypically afraid to do it? At some point in the last, say, sixty years, commitment-phobia displaced sexual neurosis as the acceptable euphemism through which men could talk about (or at least be talked about as though they talked about) the obsessive fear of castration that, from Ovid to Freud, took as its sign the phallophagic vagina. Thus, in one of the key contemporary representations of male commitment-phobia, the relationship between Chandler and Janice on Friends, our sympathetic horror derives not from Chandler's having been encompassed by Janice's body but by her postcoital laugh. To surrender, by surrendering to the feminizing procedure of commitment, one's contempt for women; to put oneself in the position where one had no choice but to put up with such a laugh—worse, perhaps, to feel compelled to excuse such a laugh among one's friends: such would be the anxious hypothesis of a heterosexual body magnetized toward feminization, but just as strongly defended from it.
Goal-setting program improves nutrition and physical activity among Supplemental Nutrition Assistance Program eligible adults
Authors: Karamanian V , Zepka B , Ernst A , West C , Grode G , Miller C
Published: May 2020

Objective:

To examine the impact of Nutrition for Life (NFL), a goal-setting nutrition education program, on the knowledge, self-efficacy and behaviour of adults eligible for Supplemental Nutrition Assistance Program-Education.

Design:

NFL was developed using a 4-week goal-setting behavioural strategy focused on nutrition, physical activity and meal planning techniques. A quantitative repeated-measures design using self-reported data was collected at pre- and post-interventions and at 1-week and 1-month follow-ups.

Setting:

Two Federally Qualified Health Centers in Philadelphia, PA, USA.

Participants:

A total of ninety-eight participants enrolled in the intervention; the majority were women (80·2 %), Black/Non-Hispanic (75·0 %) and 45–54 year old (39·6 %).

Results:

Participants showed significant improvement in knowledge, self-efficacy and behaviour. Specifically, mean daily intake for vegetables increased by 0·31 cup (P < 0·05) and for fruits by 0·39 cup (P < 0·01) at 1-week follow-up. Participants also showed healthier behaviour at 1-month follow-up. Planning at least seven meals per week increased from 14·8 to 50 % (P < 0·01), completing at least 30 min of physical activity every day in the last week increased from 16·7 to 36 % (P < 0·01) and consuming water with all meals increased from 39 to 70·6 % (P < 0·01).

Conclusions:

The implementation of a goal-oriented nutrition education program offers a promising approach at achieving positive behaviour change among SNAP-eligible adults.
Embracing Uncertainty: Modeling the Standard Uncertainty in Electron Probe Microanalysis—Part I
Authors: Ritchie Nicholas W. M.
Published: May 2020

This is the first in a series of articles which present a new framework for computing the standard uncertainty in electron excited X-ray microanalysis measurements. This article will discuss the framework and apply it to a handful of simple, but useful, subcomponents of the larger problem. Subsequent articles will handle more complex aspects of the measurement model. The result will be a framework in which sophisticated and practical models of the uncertainty for real-world measurements. It will include many long overlooked contributions like surface roughness and coating thickness. The result provides more than just error bars for our measurements. It also provides a framework for measurement optimization and, ultimately, the development of an expert system to guide both the novice and expert to design more effective measurement protocols.
The White Working Class and the 2016 Election
Authors: Carnes Nicholas , Lupu Noam
Published: May 2020

Academics and political pundits alike attribute rising support for right-wing political options across advanced democracies to the working classes. In the United States, authors claim that the white working class offered unprecedented and crucial support for Donald Trump in the 2016 election. But what is the evidence for this claim? We examine all of the available academic survey data gathered around the election, along with a number of surveys from prior elections. We test four common claims about the white working class in 2016: (1) that most Trump voters were white working-class Americans; (2) that most white working-class voters supported Trump; (3) that unusually large numbers of white working-class voters switched from Obama in 2012 to Trump in 2016; and (4) that white working-class voters were pivotal to Trump’s victory in several swing states. We find that three of the four are not supported by the available data, and the other lacks crucial context that casts doubt on the idea that Trump uniquely appealed to working-class Americans. White working-class Americans have been supporting Republican presidential candidates at higher rates in recent elections, but that process long predates 2016, and narratives that center on Trump’s alleged appeal obscure this important long-term trend.
Longevity trend risk over limited time horizons
Authors: Richards Stephen J. , Currie Iain D. , Kleinow Torsten , Ritchie Gavin P.
Published: May 2020

We consider various aspects of longevity trend risk viewed through the prism of a finite time window. We show the broad equivalence of value-at-risk (VaR) capital requirements at a p-value of 99.5% to conditional tail expectations (CTEs) at 99%. We also show how deferred annuities have higher risk, which can require double the solvency capital of equivalently aged immediate anuities. However, results vary considerably with the choice of model and so longevity trend-risk capital can only be determined through consideration of multiple models to inform actuarial judgement. This model risk is even starker when trying to value longevity derivatives. We briefly discuss the importance of using smoothed models and describe two methods to considerably shorten VaR and CTE run times.
Settling of Immiscible Droplets: A Theoretical Model for the Missing Link Between Microscopic and Outcrop Observations
Authors: Zhang Zhongtian , Wu Benjun , Wang Tao , Hui Hejiu
Published: May 2020

Liquid immiscibility is a critical mechanism to diversify magma compositions. The physical separation of exsolved melt droplets is an essential process in generating new magmas. However, little attention has been paid to this physical process. In this study, we present a new model for segregation of immiscible melt droplets in which exsolution, settling, and coalescence are all considered. The separation of immiscible droplets is similar to that of crystals in magma when the discrete melt exsolves as large (millimeter‐size) droplets and/or when the magma cools slowly. However, when immiscible melt droplets are small (micrometer‐size) and/or magma cools rapidly, coalescence can significantly enhance their separation. The low interfacial tension between coexisting silicate melts leads to the exsolution of extremely small melt droplets. Furthermore, the high viscosity of silica‐rich melt suppresses the coalescence of droplets. Consequently, the separation of highly viscous silica‐rich melt droplets is slow but could have occurred in a slowly cooling magma such as the Skaergaard intrusion. By contrast, the coalescence rate of melt droplets with low viscosity is high. Iron‐rich melt droplets, which have low viscosities, could have been separated from hydrous andesitic melts to form magnetite‐apatite ore deposits at El Laco and Marcona. Furthermore, the viscosities of sulfide and carbonatitic melts are low. Therefore, immiscibility between sulfide and silicate melts may lead to the formation of magmatic sulfide deposits, and immiscibility between carbonatitic and silicate melts can support periodical eruptions of carbonatitic lava.
Cold Cuts: Glaciers Sculpt Steep Peaks
Authors: Waldron Patricia
Published: May 2020

In environments raked by glaciers, tall peaks like Denali still survive, held up by surprisingly thin crust.
Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development
Authors: Hwang Jeong-Ryul , Byeon Yeongseon , Kim Donghwan , Park Sung-Gyoo
Published: May 2020

T cell activation requires extracellular stimulatory signals that are mainly mediated by T cell receptor (TCR) complexes. The TCR recognizes antigens on major histocompatibility complex molecules with the cooperation of CD4 or CD8 coreceptors. After recognition, TCR-induced signaling cascades that propagate signals via various molecules and second messengers are induced. Consequently, many features of T cell-mediated immune responses are determined by these intracellular signaling cascades. Furthermore, differences in the magnitude of TCR signaling direct T cells toward distinct effector linages. Therefore, stringent regulation of T cell activation is crucial for T cell homeostasis and proper immune responses. Dysregulation of TCR signaling can result in anergy or autoimmunity. In this review, we summarize current knowledge on the pathways that govern how the TCR complex transmits signals into cells and the roles of effector molecules that are involved in these pathways.
LncRNA SOX2OT promotes temozolomide resistance by elevating SOX2 expression via ALKBH5-mediated epigenetic regulation in glioblastoma
Authors: Liu Boyang , Zhou Jian , Wang Chenyang , Chi Yajie , Wei Quantang , Fu Zhao , Lian Changlin , Huang Qiongzhen , Liao Chenxin , Yang Zhao , Zeng Huijun , Xu Ningbo , Guo Hongbo
Published: May 2020

Temozolomide (TMZ) resistance is a major cause of recurrence and poor prognosis in glioblastoma (GBM). Recently, increasing evidences suggested that long noncoding RNAs (LncRNAs) modulate GBM biological processes, especially in resistance to chemotherapy, but their role in TMZ chemoresistance has not been fully illuminated. Here, we found that LncRNA SOX2OT was increased in TMZ-resistant cells and recurrent GBM patient samples, and abnormal expression was correlated with high risk of relapse and poor prognosis. Knockdown of SOX2OT suppressed cell proliferation, facilitated cell apoptosis, and enhanced TMZ sensitivity. In addition, we identified that SOX2OT regulated TMZ sensitivity by increasing SOX2 expression and further activating the Wnt5a/β-catenin signaling pathway in vitro and in vivo. Mechanistically, further investigation revealed that SOX2OT recruited ALKBH5, which binds with SOX2, demethylating the SOX2 transcript, leading to enhanced SOX2 expression. Together, these results demonstrated that LncRNA SOX2OT inhibited cell apoptosis, promoted cell proliferation, and TMZ resistance by upregulating SOX2 expression, which activated the Wnt5a/β-catenin signaling pathway. Our findings indicate that LncRNA SOX2OT may serve as a novel biomarker for GBM prognosis and act as a therapeutic target for TMZ treatment.
Correction of the tumor suppressor Salvador homolog-1 deficiency in tumors by lycorine as a new strategy in lung cancer therapy
Authors: Zhao Zhe , Xiang Shufen , Qi Jindan , Wei Yijun , Zhang Mengli , Yao Jun , Zhang Tong , Meng Mei , Wang Xiaohua , Zhou Quansheng
Published: May 2020

Salvador homolog-1 (SAV1) is a tumor suppressor required for activation of the tumor-suppressive Hippo pathway and inhibition of tumorigenesis. SAV1 is defective in several cancer types. SAV1 deficiency in cells promotes tumorigenesis and cancer metastasis, and is closely associated with poor prognosis for cancer patients. However, investigation of therapeutic strategies to target SAV1 deficiency in cancer is lacking. Here we found that the small molecule lycorine notably increased SAV1 levels in lung cancer cells by inhibiting SAV1 degradation via a ubiquitin–lysosome system, and inducing phosphorylation and activation of the SAV1-interacting protein mammalian Ste20-like 1 (MST1). MST1 activation then caused phosphorylation, ubiquitination, and degradation of the oncogenic Yes-associated protein (YAP), therefore inhibiting YAP-activated transcription of oncogenic genes and tumorigenic AKT and NF-κB signal pathways. Strikingly, treating tumor-bearing xenograft mice with lycorine increased SAV1 levels, and strongly inhibited tumor growth, vasculogenic mimicry, and metastasis. This work indicates that correcting SAV1 deficiency in lung cancer cells is a new strategy for cancer therapy. Our findings provide a new platform for developing novel cancer therapeutics.
Nondestructive ultrafast steering of a magnetic vortex by terahertz pulses
Authors: Yu Dongxing , Kang Jiyong , Berakdar Jamal , Jia Chenglong
Published: May 2020

Electric control of magnetic vortex dynamics in a reproducible way on an ultrafast time scale is a key element in the quest for efficient spintronic devices with low-energy consumption. To be useful, the control scheme should ideally be swift, be scalable, be noninvasive, and result in reliable magnetic switching. Such requirements, particularly the reproducibility of altering the vortex chirality and/or polarity, are not yet met by magnetic vortex switching via external magnetic fields, spin-polarized currents, spin waves, or laser pulses. Here, we demonstrate a novel packaged-skyrmion-mediated vortex switching process driven by a simple sequence of picosecond electrical field pulses via magnetoelectric interactions. Both the vortex chirality and polarity show a well-defined reversal behavior. The unambiguous repeated switching between four different magnetic vortex states provides an energy-efficient, highly localized, and coherent control method for nonvolatile magnetic vortex-based information storage and handling.
Raptor determines β-cell identity and plasticity independent of hyperglycemia in mice
Authors: Yin Qinglei , Ni Qicheng , Wang Yichen , Zhang Hongli , Li Wenyi , Nie Aifang , Wang Shu , Gu Yanyun , Wang Qidi , Ning Guang
Published: May 2020

Compromised β-cell identity is emerging as an important contributor to β-cell failure in diabetes; however, the precise mechanism independent of hyperglycemia is under investigation. We have previously reported that mTORC1/Raptor regulates functional maturation in β-cells. In the present study, we find that diabetic β-cell specific Raptor-deficient mice (βRapKOGFP) show reduced β-cell mass, loss of β-cell identity and acquisition of α-cell features; which are not reversible upon glucose normalization. Deletion of Raptor directly impairs β-cell identity, mitochondrial metabolic coupling and protein synthetic activity, leading to β-cell failure. Moreover, loss of Raptor activates α-cell transcription factor MafB (via modulating C/EBPβ isoform ratio) and several α-cell enriched genes i.e. Etv1 and Tspan12, thus initiates β- to α-cell reprograming. The present findings highlight mTORC1 as a metabolic rheostat for stabilizing β-cell identity and repressing α-cell program at normoglycemic level, which might present therapeutic opportunities for treatment of diabetes.
Gravitational-wave asteroseismology with fundamental modes from compact binary inspirals
Authors: Pratten Geraint , Schmidt Patricia , Hinderer Tanja
Published: May 2020

Gravitational waves (GWs) from binary neutron stars encode unique information about ultra-dense matter through characterisic signatures associated with a variety of phenomena including tidal effects during the inspiral. The main tidal signature depends predominantly on the equation of state (EoS)-related tidal deformability parameter Λ, but at late times is also characterised by the frequency of the star’s fundamental oscillation mode (f-mode). In General Relativity and for nuclear matter, Λ and the f-modes are related by universal relations which may not hold for alternative theories of gravity or exotic matter. Independently measuring Λ and the f-mode frequency enables tests of gravity and the nature of compact binaries. Here we present directly measured constraints on the f-mode frequencies of the companions of GW170817. We also show that future GW detector networks will measure f-mode frequencies to within tens of Hz, enabling precision GW asteroseismology with binary inspiral signals alone.
Formation of stable and responsive collective states in suspensions of active colloids
Authors: Bäuerle Tobias , Löffler Robert C. , Bechinger Clemens
Published: May 2020

Many animal species organise into disordered swarms, polarised flocks or swirls to protect from predators or optimise foraging. Previous studies suggest that such collective states are related to a critical point, which could explain their balance between robustness to noise and high responsiveness regarding external perturbations. Here we provide experimental evidence for this idea by investigating the stability of swirls formed by light-responsive active colloids which adjust their individual motion to positions and orientations of neighbours. Because their behaviour can be precisely tuned, controlled changes between different collective states can be achieved. During the transition between stable swirls and swarms we observe a maximum of the group’s susceptibility indicating the vicinity of a critical point. Our results support the idea of system-independent organisation principles of collective states and provide useful strategies for the realisation of responsive yet stable ensembles in microrobotic systems.
Epithelial plasticity can generate multi-lineage phenotypes in human and murine bladder cancers
Authors: Sfakianos John P. , Daza Jorge , Hu Yang , Anastos Harry , Bryant Geoffrey , Bareja Rohan , Badani Ketan K. , Galsky Matthew D. , Elemento Olivier , Faltas Bishoy M. , Mulholland David J.
Published: May 2020

Tumor heterogeneity is common in cancer, however recent studies have applied single gene expression signatures to classify bladder cancers into distinct subtypes. Such stratification assumes that a predominant transcriptomic signature is sufficient to predict progression kinetics, patient survival and treatment response. We hypothesize that such static classification ignores intra-tumoral heterogeneity and the potential for cellular plasticity occurring during disease development. We have conducted single cell transcriptome analyses of mouse and human model systems of bladder cancer and show that tumor cells with multiple lineage subtypes not only cluster closely together at the transcriptional level but can maintain concomitant gene expression of at least one mRNA subtype. Functional studies reveal that tumor initiation and cellular plasticity can initiate from multiple lineage subtypes. Collectively, these data suggest that lineage plasticity may contribute to innate tumor heterogeneity, which in turn carry clinical implications regarding the classification and treatment of bladder cancer.
Constructing chiral bicyclo[3.2.1]octanes via palladium-catalyzed asymmetric tandem Heck/carbonylation desymmetrization of cyclopentenes
Authors: Yuan Zhenbo , Zeng Yuye , Feng Ziwen , Guan Zhe , Lin Aijun , Yao Hequan
Published: May 2020

Transition-metal-catalyzed tandem Heck/carbonylation reaction has emerged as a powerful tool for the synthesis of structurally diverse carbonyl molecules, as well as natural products and pharmaceuticals. However, the asymmetric version was rarely reported, and remains a challenging topic. Herein, we describe a palladium-catalyzed asymmetric tandem Heck/carbonylation desymmetrization of cyclopentenes. Alcohols, phenols and amines are employed as versatile coupling reagents for the construction of multifunctional chiral bicyclo[3.2.1]octanes with one all-carbon quaternary and two tertiary carbon stereogenic centers in high diastereo- and enantioselectivities. This study represents an important progress in both the asymmetric tandem Heck/carbonylation reactions and enantioselective difunctionalization of internal alkenes.
Density-dependence tips the change of plant–plant interactions under environmental stress
Authors: Zhang Ruichang , Tielbörger Katja
Published: May 2020

Facilitation studies typically compare plants under differential stress levels with and without neighbors, while the density of neighbors has rarely been addressed. However, recent empirical studies indicate that facilitation may be density-dependent too and peak at intermediate neighbor densities. Here, we propose a conceptual model to incorporate density-dependence into theory about changes of plant–plant interactions under stress. To test our predictions, we combine an individual-based model incorporating both facilitative response and effect, with an experiment using salt stress andArabidopsis thaliana. Theoretical and experimental results are strikingly consistent: (1) the intensity of facilitation peaks at intermediate density, and this peak shifts to higher densities with increasing stress; (2) this shift further modifies the balance between facilitation and competition such that the stress-gradient hypothesis applies only at high densities. Our model suggests that density-dependence must be considered for predicting plant–plant interactions under environmental change.
Glycopeptide epitope facilitates HIV-1 envelope specific humoral immune responses by eliciting T cell help
Authors: Sun Lina , Paschall Amy V. , Middleton Dustin R. , Ishihara Mayumi , Ozdilek Ahmet , Wantuch Paeton L. , Aceil Javid , Duke Jeremy A. , LaBranche Celia C. , Tiemeyer Michael , Avci Fikri Y.
Published: May 2020

The inherent molecular complexity of human pathogens requires that mammals evolved an adaptive immune system equipped to handle presentation of non-conventional MHC ligands derived from disease-causing agents, such as HIV-1 envelope (Env) glycoprotein. Here, we report that a CD4+ T cell repertoire recognizes a glycopeptide epitope on gp120 presented by MHCII pathway. This glycopeptide is strongly immunogenic in eliciting glycan-dependent cellular and humoral immune responses. The glycopeptide specific CD4+ T cells display a prominent feature of Th2 and Th17 differentiation and exert high efficacy and potency to help Env trimer humoral immune responses. Glycopeptide-induced CD4+ T cell response prior to Env trimer immunization elicits neutralizing antibody development and production of antibodies facilitating uptake of immunogens by antigen-presenting cells. Our identification of gp120 glycopeptide–induced, T cell–specific immune responses offers a foundation for developing future knowledge-based vaccines that elicit strong and long-lasting protective immune responses against HIV-1 infection.
Long-term alterations in brain and behavior after postnatal Zika virus infection in infant macaques
Authors: Raper Jessica , Kovacs-Balint Zsofia , Mavigner Maud , Gumber Sanjeev , Burke Mark W. , Habib Jakob , Mattingly Cameron , Fair Damien , Earl Eric , Feczko Eric , Styner Martin , Jean Sherrie M. , Cohen Joyce K. , Suthar Mehul S. , Sanchez Mar M. , Alvarado Maria C. , Chahroudi Ann
Published: May 2020

Zika virus (ZIKV) infection has a profound impact on the fetal nervous system. The postnatal period is also a time of rapid brain growth, and it is important to understand the potential neurobehavioral consequences of ZIKV infection during infancy. Here we show that postnatal ZIKV infection in a rhesus macaque model resulted in long-term behavioral, motor, and cognitive changes, including increased emotional reactivity, decreased social contact, loss of balance, and deficits in visual recognition memory at one year of age. Structural and functional MRI showed that ZIKV-infected infant rhesus macaques had persistent enlargement of lateral ventricles, smaller volumes and altered functional connectivity between brain areas important for socioemotional behavior, cognitive, and motor function (e.g. amygdala, hippocampus, cerebellum). Neuropathological changes corresponded with neuroimaging results and were consistent with the behavioral and memory deficits. Overall, this study demonstrates that postnatal ZIKV infection in this model may have long-lasting neurodevelopmental consequences.
Peripheral nerve resident macrophages share tissue-specific programming and features of activated microglia
Authors: Wang Peter L. , Yim Aldrin K. Y. , Kim Ki-Wook , Avey Denis , Czepielewski Rafael S. , Colonna Marco , Milbrandt Jeffrey , Randolph Gwendalyn J.
Published: May 2020

Whereas microglia are recognized as fundamental players in central nervous system (CNS) development and function, much less is known about macrophages of the peripheral nervous system (PNS). Here, by comparing gene expression across neural and conventional tissue-resident macrophages, we identified transcripts that were shared among neural resident macrophages as well as selectively enriched in PNS macrophages. Remarkably, PNS macrophages constitutively expressed genes previously identified to be upregulated by activated microglia during aging, neurodegeneration, or loss of Sall1. Several microglial activation-associated and PNS macrophage-enriched genes were also expressed in spinal cord microglia at steady state. We further show that PNS macrophages rely on IL-34 for maintenance and arise from both embryonic and hematopoietic precursors, while their expression of activation-associated genes did not differ by ontogeny. Collectively, these data uncover shared and unique features between neural resident macrophages and emphasize the role of nerve environment for shaping PNS macrophage identity.
Real-time terahertz imaging with a single-pixel detector
Authors: Stantchev Rayko Ivanov , Yu Xiao , Blu Thierry , Pickwell-MacPherson Emma
Published: May 2020

Terahertz (THz) radiation is poised to have an essential role in many imaging applications, from industrial inspections to medical diagnosis. However, commercialization is prevented by impractical and expensive THz instrumentation. Single-pixel cameras have emerged as alternatives to multi-pixel cameras due to reduced costs and superior durability. Here, by optimizing the modulation geometry and post-processing algorithms, we demonstrate the acquisition of a THz-video (32 × 32 pixels at 6 frames-per-second), shown in real-time, using a single-pixel fiber-coupled photoconductive THz detector. A laser diode with a digital micromirror device shining visible light onto silicon acts as the spatial THz modulator. We mathematically account for the temporal response of the system, reduce noise with a lock-in free carrier-wave modulation and realize quick, noise-robust image undersampling. Since our modifications do not impose intricate manufacturing, require long post-processing, nor sacrifice the time-resolving capabilities of THz-spectrometers, their greatest asset, this work has the potential to serve as a foundation for all future single-pixel THz imaging systems.