bluuebunny/crossref_metadata_2025_split huggingface dataset:
m6A demethylase ALKBH5 promotes tumor cell proliferation by destabilizing IGF2BPs target genes and worsens the prognosis of patients with non-small cell lung cancer
Authors: Tsuchiya Kazuo , Yoshimura Katsuhiro , Iwashita Yuji , Inoue Yusuke , Ohta Tsutomu , Watanabe Hirofumi , Yamada Hidetaka , Kawase Akikazu , Tanahashi Masayuki , Ogawa Hiroshi , Funai Kazuhito , Shinmura Kazuya , Suda Takafumi , Sugimura Haruhiko 
Published: July 2021

AbstractThe modification of N6-methyladenosine (m6A) in RNA and its eraser ALKBH5, an m6A demethylase, play important roles across various steps of human carcinogenesis. However, the involvement of ALKBH5 in non-small cell lung cancer (NSCLC) development remains to be completely elucidated. The current study revealed that the expression of ALKBH5 were increased in NSCLC and increased expression of ALKBH5 worsened the prognosis of patients with NSCLC. In vitro study revealed that ALKBH5 knockdown suppressed cell proliferation ability of PC9 and A549 cells as well as promoted G1 arrest and increased the number of apoptotic cells. Furthermore, ALKBH5 overexpression increased the cell proliferation ability of the immortalized cell lines. Microarray analysis and western blotting revealed that the expression of CDKN1A or TIMP3 were increased by ALKBH5 knockdown. These alterations were offset by a double knockdown of both ALKBH5 and one of the IGF2BPs. The decline of mRNAs was, at least partly, owing to the destabilization of these mRNAs by one of the IGF2BPs. In conclusions, the ALKBH5–IGF2BPs axis promotes cell proliferation and tumorigenicity, which in turn causes the unfavorable prognosis of NSCLC.
Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states
Authors: Al-Dalahmah Osama , Argenziano Michael G. , Kannan Adithya , Mahajan Aayushi , Furnari Julia , Paryani Fahad , Boyett Deborah , Save Akshay , Humala Nelson , Khan Fatima , Li Juncheng , Lu Hong , Sun Yu , Tuddenham John F. , Goldberg Alexander R. , Dovas Athanassios , Banu Matei A. , Sudhakar Tejaswi , Bush Erin , Lassman Andrew B. , McKhann Guy M. , Gill Brian J. A. , Youngerman Brett , Sisti Michael B. , Bruce Jeffrey N. , Sims Peter A. , Menon Vilas , Canoll Peter 
Published: July 2021

AbstractGlioblastoma (GBM) is an aggressive diffusely infiltrating neoplasm that spreads beyond surgical resection margins, where it intermingles with non-neoplastic brain cells. This complex microenvironment harboring infiltrating glioma and non-neoplastic brain cells is the origin of tumor recurrence. Thus, understanding the cellular and molecular features of the glioma microenvironment is therapeutically and prognostically important. We used single-nucleus RNA sequencing (snRNAseq) to determine the cellular composition and transcriptional states in primary and recurrent glioma and identified three compositional ‘tissue-states’ defined by the observed patterns of cohabitation between neoplastic and non-neoplastic brain cells. These comprise states enriched in A) neurons and non-neoplastic glia, B) reactive astrocytes and inflammatory cells, and C) proliferating tumor cells. The tissue states also showed distinct associations with the different transcriptional states of GBM cells. Spatial transcriptomics revealed that the cell-types/transcriptional-states associated with each tissue state colocalize in space. Tissue states are clinically significant because they correlate with radiographic, histopathologic, and prognostic features. Importantly, we found that our compositionally-defined tissue states are enriched in distinct metabolic pathways. One such pathway is fatty acid biosynthesis, which was enriched in tissue state B – a state enriched in recurrent glioblastoma and associated with shorter overall survival- and composed of astrocyte-like/mesenchymal glioma cells, reactive astrocytes, and monocyte-like myeloid cells. We showed that treating acute slices of GBM with a fatty acid synthesis inhibitor is sufficient to deplete the transcriptional signature of tissue state B. Our findings define a novel compositional approach to analyze glioma-infiltrated tissue which allows us to discover prognostic and targetable features, paving the way to new mechanistic and therapeutic discoveries.
Chronic CNS Pathology is Associated with Abnormal Collagen Deposition and Fibrotic-like Changes
Authors: Macapagal Daphne Palacios , Cann Jennifer , Cresswell Georgia , Zerrouki Kamelia , Dacosta Karma , Wang Jingya , Connor Jane , Davidson Todd S. 
Published: July 2021

AbstractMultiple sclerosis is a chronic debilitating disease of the CNS. The relapsing remitting form of the disease is driven by CNS directed inflammation. However, in the progressive forms of the disease, inflammation has abated and the underlying pathology is less well understood. In this paper, we show that chronic lesions in progressive MS are associated with fibrotic changes, a type of pathology that has previously not thought to occur in the CNS. In an animal model of chronic MS, late stage disease contains no inflammatory infiltrates and is instead characterized by collagen deposition that is histologically similar to fibrosis. In human MS samples, chronic, but not acute lesions, are devoid of inflammatory infiltrates and instead contain significant collagen deposition. Furthermore, we demonstrate that both mouse and human astrocytes are the cellular source of collagen. These results suggest that anti-fibrotic therapy may be beneficial in the treatment of progressive MS.
Comparative transcriptomics of tropical woody plants supports fast and furious strategy along the leaf economics spectrum in lianas
Authors: Sezen U. Uzay , Worthy Samantha J. , Umaña Maria N. , Davies Stuart J. , McMahon Sean M. , Swenson Nathan G. 
Published: July 2021

AbstractLianas, climbing woody plants, influence the structure and function of tropical forests. Climbing traits have evolved multiple times, including ancestral groups such as gymnosperms and pteridophytes, but the genetic basis of the liana strategy is largely unknown. Here, we use a comparative transcriptomic approach for 47 tropical plant species, including ten lianas of diverse taxonomic origins, to identify genes that are consistently expressed or downregulated only in lianas. Our comparative analysis of full-length transcripts enabled the identification of a core interactomic network common to lianas. Sets of transcripts identified from our analysis reveal features related to functional traits pertinent to leaf economics spectrum in lianas, include upregulation of genes controlling epidermal cuticular properties, cell wall remodeling, carbon concentrating mechanism, cell cycle progression, DNA repair and a large suit of downregulated transcription factors and enzymes involved in ABA-mediated stress response as well as lignin and suberin synthesis. All together, these genes are known to be significant in shaping plant morphologies through responses such as gravitropism, phyllotaxy and shade avoidance.
Area-based conservation planning in Japan: protected area network effectiveness to the post-2020 Global Biodiversity Framework
Authors: Shiono Takayuki , Kubota Yasuhiro , Kusumoto Buntarou 
Published: July 2021

ABSTRACTTo reframe the imperfect review processes of nation-scale actions on area-based conservation through protected area (PA) networks, we first created novel infrastructure to visualize nation-level biodiversity information in Japan. We then assessed the performance of the existing PA network relative to land exploitation pressure and evaluated conservation effectiveness of PA expansion for the post-2020 Global Biodiversity Framework. The Zonation algorithm was used to spatially prioritize conservation areas to minimize biodiversity loss and the extinction risk for 8,500 Japanese vascular plant and vertebrate species under constraints of the existing PA network and land use. The spatial pattern of the identified priority areas, which were considered candidate areas for expansion of the current PA network, was influenced by land-use types according to the mask layers of non-PAs, and low-, middle-, and high-ranked PAs. The current PA network reduced the aggregate extinction risk of multiple species by 36.6%. Indeed, the percentage of built-up areas in the existing PAs was in general smaller than that in the areas surrounding PAs. Notably, high-ranked PAs fully restrained built-up pressure (0.037% per 10 years), whereas low-ranked PAs in the national park and wild-life protection areas did not (1.845% per 10 years). Conservation effects were predicted to substantially improve by expansion of high-ranked (legally strict) PAs into remote non-PAs without population/socio-economic activities, or expansion of medium-ranked PAs into agriculture forestry satoyama and urban areas. A 30% land conservation target was predicted to decrease extinction risk by 74.1% when PA expansion was implemented across remote areas, satoyama, and urban areas; moreover, PA connectivity almost doubled compared with the existing PA network. In contrast, a conventional scenario showed that placing national parks in state-owned and non-populated areas would reduce extinction risk by only 4.0%. The conservation prioritization analyses demonstrated an effectiveness of using a comprehensive conservation approach that reconciles land-sparing protection and land-sharing conservation in other effective area-based conservation measures (OECM) in satoyama and urban green spaces. Our results revealed that complementary inclusion of various PAs interventions related to their governance and land-use planning plays a critical role in effectively preventing biodiversity loss and makes it more feasible to achieve ambitious conservation targets.
Linking individual differences in cognitive control and perception: Meta-perception in older and younger adults
Authors: Klever Lena , Mamassian Pascal , Billino Jutta 
Published: July 2021

AbstractVisual perception is not only shaped by sensitivity, but also by confidence, i.e. the ability to estimate the accuracy of a visual decision. There is robust evidence that younger observers have access to a reliable measure of their own uncertainty when making visual decisions. This metacognitive ability might be challenged during aging due to increasing sensory noise and decreasing cognitive control resources. We investigated age effects on visual confidence using a confidence forced-choice paradigm. We determined discrimination thresholds for trials in which perceptual judgements were indicated as confident and for those in which they were declined as confident. Younger adults (19-38 years) showed significantly lower discrimination thresholds than older adults (60-78 years). In both age groups, perceptual performance was linked to confidence judgements, but overall results suggest reduced confidence efficiency in older adults. However, we observed substantial variability of confidence effects across all particpants. This variability was closely linked to individual differences in cognitive control capacities, i.e. executive function. Our findings provide evidence for age-related differences in meta-perceptual efficiency that present a specific challenge to perceptual performance in old age. We propose that these age effects are primarily mediated by cognitive control resources, supporting their crucial role for metacognitive efficiency.
SARS-CoV-2 promotes microglial synapse elimination in human brain organoids
Authors: Samudyata  , Oliveira Ana Osório , Malwade Susmita , de Sousa Nuno Rufino , Goparaju Sravan K , Lekander Jessica Gracias , Orhan Funda , Steponaviciute Laura , Schalling Martin , Sheridan Steven D , Perlis Roy H. , Rothfuchs Antonio , Sellgren Carl M. 
Published: July 2021

ABSTRACTNeuropsychiatric manifestations are common in both the acute and post-acute phase of SARS-CoV-2 infection, but the mechanisms of these effects are unknown. In a newly established brain organoid model with innately developing microglia, we demonstrate that SARS-CoV-2 infection causes an extensive cell death and loss of post-synaptic termini. Despite limited neurotropism and a decelerating viral replication, we observe a threefold increase in microglial engulfment of postsynaptic termini after SARS-CoV-2 exposure. We define the microglial responses to SARS-CoV-2 infection by single cell transcriptomic profiling and observe an upregulation of interferon-responsive genes as well as genes promoting migration and synaptic stripping. To a large extent, SARS-CoV-2 exposed microglia display a transcriptomic profile previously observed in neurodegenerative disorders characterized by early a synapse loss and an increased incident risk after a Covid-19 infection. Our results reveal that brain organoids infected with SARS-CoV-2 display disruption in circuit integrity via microglia-mediated synapse elimination and identifies a potential novel mechanism contributing to cognitive impairments in patients recovering from Covid-19.
Talent management practices: perception of registered nurses in Malawian public hospitals
Authors: Dzimbiri George Lewis , Molefakgotla Alex Molefi 
Published: July 2021

PurposeThe purpose of this study is to investigate nurses’ perception towards the current application of talent management practices in Malawian public hospitals. It further explores whether significant differences exist between the registered nurses’ perceptions of the current application of talent management practices based on their demographic factors.Design/methodology/approachThe study employed a quantitative research approach, using a cross-sectional survey strategy. An adapted version of Human Capital Index (HCI) questionnaire with 45-items was administered amongst 947 registered nurses in four public hospitals. Eventually, 580 responses, representing 61.2 per cent were found to be acceptable for analysis. Stata version-16 software programme was used to analyse the data.FindingsFindings of the study demonstrated that talent management practices are currently poorly applied amongst the nurses. Substantial gaps existed between the current applications versus the importance of talent management practices. Significant differences exist between the nurses perceptions of talent management practices based on their marital status.Research limitations/implicationsThe study only focused on a single perspective (registered nurses) and a single area (Malawian public hospitals) – an issue that disregarded different views (e.g. doctors, hospital administrators, hospital directors and other hospital staff). Furthermore, the results of this study cannot be generalised to other public and private hospitals settings because the data were collected from central hospitals only.Practical implicationsPractically, this study highlights the problematic areas of talent management practices hence the need for effective talent management for nurses.Social implicationsThe study has huge social implications in that the results will inform best practices for public hospitals thereby improving welfare of the patients and society at large.Originality/valueThe study contributes to new knowledge on nurses’ perception towards the application of talent management practices within the Malawian health sector and presents a valid and reliable measure to assess their perception.
Omnichannel promotions and their effect on customer satisfaction
Authors: Blom Angelica , Lange Fredrik , Hess Ronald L. 
Published: July 2021

Purpose
This paper aims to investigate whether customer satisfaction varies when presented with different types of omnichannel promotions (shopping goal-congruent vs shopping goal-incongruent and monetary vs non-monetary promotions) and if the effect on satisfaction is mediated by service excellence. In addition, this paper examines whether consumers respond differently to these promotions when shopping for utilitarian or hedonic products or when they have an inherent utilitarian or hedonic shopping motivation.

Design/methodology/approach
Two online shopping scenario experiments are conducted. Study 1 (n = 1,034) differentiates effects of omnichannel promotions between hedonic and utilitarian product categories. Study 2 (n = 345) contrasts hedonic and utilitarian shopping motivation in the same product category.

Findings
The findings in this paper demonstrate positive effects from both presenting a shopping goal congruent and a monetary promotion in an omnichannel setting on customer satisfaction. The positive effects are explained by service excellence and are demonstrated to be attenuated in the hedonic product category and for consumers with a hedonic shopping motivation.

Research limitations/implications
The effect of omnichannel promotions was demonstrated using a scenario-based experimental approach, future research should use field experiments.

Practical implications
The findings in this paper demonstrate practical implications for a retailer who wishes to optimize its omnichannel promotion strategy across channels and touchpoints.

Originality/value
To date there is little directions for retailers on how to optimize their omnichannel promotion strategy. This paper contributes to research and practice by demonstrating that shopping goal-congruent promotions (vs in-congruent) and monetary promotions (vs non-monetary) increase customer satisfaction more in an omnichannel context. The effects are enhanced for utilitarian (vs hedonic) products/shopping motivation.
Budgetary restrictions and ethical behaviours in a hospital context – evidence from general surgeons
Authors: Silva Cristina Piedade , Sousa Rita Martins de 
Published: July 2021

Purpose
The purpose of this paper is to study how budgetary constraints can have ethical implications on patient treatment options.

Design/methodology/approach
By applying a qualitative methodological approach (interviews) and participant observation, this paper studies the behaviour of surgeons in scenarios of financial restriction.

Findings
The empirical findings show that despite the conflict between the economy and the leges artis, surgeons maintain the ethical and deontological principles of their profession with fair rules of orientation.

Practical implications
The importance of this study can be realised by its continuity. One of the authors is already implicated on a wider research to investigate the influence of the economic scarcity of resources on general surgeons’ ethical behaviours.

Social implications
This paper is a contribution to understanding the rules that restrain the activities of surgeons. Politicians sometimes do not have a full understanding of the pressures that the medical profession faces in their day-to-day activities. Currently, with the addition of problems relate to COVID-19, politicians and populations seem to better understand the importance of the Serviço Nacional de Saúde (SNS), This paper hopes that this understanding will be not only a conjectural moment.

Originality/value
In conjunction with the economic recession that began in the first decade of this century, health institutions have long faced budgetary constraints that condition their material and human resources and correspondingly shape the scope of health professional activities. Until now, it has not been studied the impact of economic crises on the ethical behaviour of Portuguese surgeons. Therefore, this research is a first step and a useful contribution to understanding the rules that can restrain (or not) the ethical conduct of these health professionals.
Cultivating coffee experiences in the Eje Cafetero, Colombia
Authors: Bowen Robert 
Published: July 2021

Purpose
This paper aims to investigate the potential for developing a unique coffee tourism experience in the Eje Cafetero region of Colombia, considering unique local traditions of coffee production, as well as local tourism infrastructure.

Design/methodology/approach
With the aim of observing coffee tourism experiences in-place, this paper uses an analytical auto-ethnographic methodology, where the researcher observes the coffee tourism experience, considering both the tourism providers and tourists. This represents an emerging method in tourism research with data collected through a reflective diary and photographic documentation.

Findings
Coffee tourism has already established itself in the Eje Cafetero region, and with increasing tourism in Colombia, there is potential for further interest in coffee tourism in the region. With an established infrastructure and positive reputation for coffee, Colombia is well placed to provide various coffee tourism offerings, including unique experiences based on local traditions.

Originality/value
Coffee tourism is an under-researched area, with few studies based on primary data to understand the potential for coffee tourism experiences. This study advances knowledge on this while also promoting innovative auto-ethnographic research methods. Findings help places understand how to leverage competitive advantage through unique offerings.
Advances in robotic prostheses
Authors: Bogue Rob 
Published: July 2021

Purpose
This paper aims to provide details of recent advances in robotic prostheses with the emphasis on the control and sensing technologies.

Design/methodology/approach
Following a short introduction, this paper first discusses the main robotic prosthesis control strategies. It then provides details of recent research and developments using non-invasive and invasive brain–computer interfaces (BCIs). These are followed by examples of studies that seek to confer robotic prostheses with sensory feedback. Finally, brief conclusions are drawn.

Findings
A significant body of research is underway involving electromyographic and BCI technologies, often in combination with advanced data processing and analysis schemes. This has the potential to yield robotic prostheses with advanced capabilities such as greater dexterity and sensory feedback.

Originality/value
This illustrates how electromyographic, BCI, signal processing and sensor technologies are being used to create robotic prostheses with enhanced functionality.
A new approach for hybrid (PID + MRAC) adaptive controller applied to two-axes McKibben muscle manipulator: a mechanism for human-robot collaboration
Authors: Bomfim Marcelo Henrique Souza , Lima II Eduardo José , Monteiro Neemias Silva , Sena Vinícius Avelino 
Published: July 2021

Purpose
This paper aims to present a new approach, called hybrid model reference adaptive controller or H-MRAC, for the hybrid controller (proportional-integral-derivative [PID + MRAC]) that will be used to control the position of a pneumatic manipulator.

Design/methodology/approach
It was developed a McKibben muscle using nautical mesh, latex and high-density polyethene connectors and it was constructed an elbow manipulator with two degrees of freedom, driven by these muscles. Then it was presented the H-MRAC control law based on the phenomenological characteristics of the plant, aiming at fast response and low damping. Lyapunov's theory was used as the project methodology, which ensures asymptotic stability for the control system.

Findings
It was developed a precise control system for a pneumatic manipulator and the results were compared to previous research.

Research limitations/implications
In collaborative robotics, human and machine occupy the same workspace. This research promotes the development of safer and more complacent mechatronic systems in the event of collisions.

Practical implications
As a practical implication, the research allows the substitution of electric motors by McKibben muscles in industrial robots with high accuracy.

Social implications
The pneumatic manipulator will make the human-robot physical interaction safer as it can prevent catastrophic collisions causing victims or equipment breakdown.

Originality/value
When compared to results in the literature, the present research showed a 37.51% and 36.74% lower global error in position tracking than MRAC and Adaptive proportional-integral-derivative (A-PID), respectively, validating its effectiveness.