bluuebunny/crossref_metadata_2025_split huggingface dataset:
Random clonal expansion as a limiting factor in transplantable in vivo CRISPR/Cas9 screens
Authors: Lee Tet Woo , Hunter Francis W. , Wilson William R. , Jamieson Stephen M.F. 
Published: November 2021

AbstractTransplantable in vivo CRISPR/Cas9 knockout screens, in which cells are transduced in vitro and inoculated into mice to form tumours in vivo, offer the opportunity to evaluate gene function in a cancer model that incorporates the multicellular interactions of the tumour microenvironment. In this study, we sought to develop a head and neck squamous cell carcinoma (HNSCC) tumour xenograft model for whole-genome screens that could maintain high gRNA representation during tumour initiation and progression. To achieve this, we sought early-passage HNSCC cell lines with a high frequency of tumour initiation-cells, and identified the pseudodiploid UT-SCC-54C line as a suitable model from 23 HNSCC lines tested based on a low tumourigenic dose for 50% takes (TD50) of 1100 cells in NSG mice. On transduction with the GeCKOv2 whole-genome gRNA library (119,461 unique gRNAs), high (80-95%) gRNA representation was maintained in early (up to 14 d) UT-SCC-54C tumours in NSG mice, but not in UT-SCC-74B tumours (TD50=9200). However, loss of gRNA representation was observed in UT-SCC-54C tumours following growth for 38-43 days, which correlated with a large increase in bias among gRNA read counts due to stochastic expansion of clones in the tumours. Applying binomial thinning simulations revealed that the UT-SCC-54C model would have 40-90% statistical power to detect drug sensitivity genes with log2 fold change effect sizes of 1-2 in early tumours with gRNA libraries of up to 10,000 gRNAs and modest group sizes of 5 tumours. In large tumours, this model would have had 45% power to detect log2 fold change effect sizes of 2-3 with libraries of 2,000 gRNAs and 14 tumours per group. Based on our findings, we conclude that gRNA library size, sample size and tumour size are all parameters that can be individually optimised to ensure transplantable in vivo CRISPR screens can successfully evaluate gene function.
The gradient model of brain organization in decisions involving ‘empathy for pain’
Authors: Labek Karin , Sittenberger Elisa , Kienhöfer Valerie , Rabl Luna , Messina Irene , Schurz Matthias , Stingl Julia C. , Viviani Roberto 
Published: November 2021

AbstractInfluential models of cortical organization propose a close relationship between heteromodal association areas and highly connected hubs in the default mode network. The ‘gradient model’ of cortical organization proposes a close relationship between these areas and highly connected hubs in the default mode network, a set of cortical areas deactivated by demanding tasks. Here, we used a decision-making task and representational similarity analysis with classic ‘empathy for pain’ stimuli to probe the relationship between high-level representations of imminent pain in others and these areas. High-level representations were co-localized with task deactivations or the transitions from activations to deactivations. These loci belonged to two groups: those that loaded on the high end of the principal cortical gradient and were associated by meta-analytic decoding with the default mode network, and those that appeared to accompany functional repurposing of somatosensory cortex in the presence of visual stimuli. In contrast to the nonspecific meta-analytic decoding of these loci, low-level representations, such as those of body parts involved in pain or of pain itself, were decoded with matching topics terms. These findings suggest that task deactivations may set out cortical areas that host high-level representations. We anticipate that an increased understanding of the cortical correlates of high-level representations may improve neurobiological models of social interactions and psychopathology.
Sex differences in choice-based thermal nociceptive tasks in adult rats
Authors: Bourgeois JR , Kopec AM 
Published: November 2021

ABSTRACTInterest in the role of sex as a biological variable continues to increase, including a mandate for the study of both sexes in NIH-funded research. Choice-based thermal nociceptive tests allow for the study of a more spontaneous response to thermal stimuli and avoidance behavior compared to traditional nociceptive assays, and their usage has been increasing in recent years. However, to date no comparison of naïve male and female responses to such tests has been published. As sex differences are known to exist in both human chronic pain conditions and rodent models of nociception, it is critical to understand the impact of sex on any nociceptive assay. Herein, we examined the effect of sex on two choice-based thermal nociceptive tests, the thermal gradient test and the temperature place preference test, in adult rats. We report that marked sex differences exist in responses to these tests. Namely, the activation of a 10° C-to-47° C thermal gradient results in an increase in time spent in the 10° C zone in females, compared to a reduction in males. In a temperature place preference test pairing a surface temperature of 22° C with either 5° C, 10° C, 47° C, or 50° C, males spent less than 50% of their time in every non-22° C zone, but in females this was only observed when testing 50° C. Together, these results suggest that male rats show more avoidance behavior to non-ambient temperatures when given free access to multiple zones, including at temperatures which are milder than those typically used to evoke a nociceptive response in traditional hot and cold plate tests.
Hippocampal-Prefrontal cortex network dynamics predict performance during retrieval in a context-guided object memory task
Authors: Morici JF , Weisstaub NV , Zold CL 
Published: November 2021

AbstractRemembering life episodes is a complex process that requires the interaction between multiple brain areas. It is thought that contextual information provided by the hippocampus (HPC) can trigger the recall of a past event through the activation of medial prefrontal cortex (mPFC) neuronal ensembles, but the underlying mechanisms remain poorly understood. Indeed, little is known about how the vHPC and mPFC are coordinated during a contextual-guided recall of an object recognition memory. To address this, we performed electrophysiological recordings in behaving rats during the retrieval phase of the object-in-context memory task (OIC). Coherence, phase locking and theta amplitude correlation analysis showed an increase in vHPC-mPFC LFP synchronization in the theta range when animals explore contextually mismatched objects. Moreover, we identified ensembles of putative pyramidal cells in the mPFC that encode specific object-context associations. Interestingly, the increase of vHPC-mPFC synchronization during exploration of the contextually mismatched object and the preference of mPFC incongruent object neurons predicts the animals’ performance during the resolution of the OIC task. Altogether, these results identify changes in vHPC-mPFC synchronization and mPFC ensembles encoding specific object-context associations likely involved in the recall of past events.
Neuronal activity in the human amygdala and hippocampus enhances emotional memory encoding
Authors: Qasim Salman E. , Mohan Uma R. , Stein Joel M. , Jacobs Joshua 
Published: November 2021

SummaryEmotional events comprise our strongest and most valuable memories, yet it is unknown how the brain prioritizes emotional information for storage. Here, we examined the neural basis of this prioritization using direct brain recording, deep brain stimulation, and psychometric assessment, with human subjects performing an episodic memory task in which they showed improved performance for emotional stimuli. During the task, high-frequency activity (HFA), a correlate of neuronal spiking activity, increased in both the hippocampus and amygdala when subjects successfully encoded emotionally arousing stimuli. Applying inhibitory electrical stimulation to these regions decreased HFA and specifically reversed the enhancement of memory for emotional stimuli, indicating that neuronal activity in the amygdalohippocampal circuit has a direct role in prioritizing emotional memories. Finally, we found abnormal patterns of amygdalohippocampal HFA in depressed individuals which correlated with a bias for negative memories in these subjects. Going forward, targeted modulation that upregulates neuronal excitation in the amygdalohippocampal circuit may have a causal and translational role in modulating emotional memory.
Archetypal Analysis for Population Genetics
Authors: Gimbernat-Mayol Julia , Montserrat Daniel Mas , Bustamante Carlos D. , Ioannidis Alexander G. 
Published: November 2021

AbstractThe estimation of genetic clusters using genomic data has application from genome-wide association studies (GWAS) to demographic history to polygenic risk scores (PRS) and is expected to play an important role in the analyses of increasingly diverse, large-scale cohorts. However, existing methods are computationally-intensive, prohibitively so in the case of nationwide biobanks. Here we explore Archetypal Analysis as an efficient, unsupervised approach for identifying genetic clusters and for associating individuals with them. Such unsupervised approaches help avoid conflating socially constructed ethnic labels with genetic clusters by eliminating the need for exogenous training labels. We show that Archetypal Analysis yields similar cluster structure to existing unsupervised methods such as ADMIXTURE and provides interpretative advantages. More importantly, we show that since Archetypal Analysis can be used with lower-dimensional representations of genetic data, significant reductions in computational time and memory requirements are possible. When Archetypal Analysis is run in this fashion, it takes several orders of magnitude less compute time than the current standard, ADMIXTURE. Finally, we demonstrate uses ranging across datasets from humans to canids.Author summaryThis work introduces a method that combines the singular value decomposition (SVD) with Archetypal Analysis to perform fast and accurate genetic clustering by first reducing the dimensionality of the space of genomic sequences. Each sequence is described as a convex combination (admixture) of archetypes (cluster representatives) in the reduced dimensional space. We compare this interpretable approach to the widely used genetic clustering algorithm, ADMIXTURE, and show that, without significant degradation in performance, Archetypal Analysis outperforms, offering shorter run times and representational advantages. We include theoretical, qualitative, and quantitative comparisons between both methods.
Impact of the COVID-19 pandemic on the malaria burden in northern Ghana: Analysis of routine surveillance data
Authors: Heuschen Anna-Katharina , Abdul-Mumin Alhassan , Adokiya Martin Nyaaba , Lu Guangyu , Jahn Albrecht , Razum Oliver , Winkler Volker , Müller Olaf 
Published: November 2021

AbstractIntroductionThe COVID-19 pandemic and its collateral damage severely impact health systems globally and risk to worsen the malaria situation in endemic countries. Malaria is a leading cause of morbidity and mortality in Ghana. This study aims to analyze routine surveillance data to assess possible effects on the malaria burden in the first year of the COVID-19 pandemic in the Northern Region of Ghana.MethodsMonthly routine data from the District Health Information Management System II (DHIMS2) of the Northern Region of Ghana were analyzed. Overall outpatient department visits and malaria incidence rates from the years 2015 to 2019 were compared to the corresponding data of the year 2020.ResultsCompared to the corresponding periods of the years 2015 to 2019, overall visits and malaria incidence in pediatric and adult outpatient departments in northern Ghana decreased in March and April 2020, when major movement and social restrictions were implemented in response to the pandemic. Incidence slightly rebounded afterwards in 2020 but stayed below the average of the previous years. Data from inpatient departments showed a similar but more pronounced trend when compared to outpatient departments. In pregnant women, however, malaria incidence in outpatient departments increased after the first COVID-19 wave.DiscussionThe findings from this study show that the COVID-19 pandemic affects the malaria burden in health facilities of Ghana, with declines in in- and outpatient rates. Pregnant women may experience reduced access to intermittent preventive malaria treatment and insecticide treated nets, resulting in subsequent higher malaria morbidity. Further data from other African countries, particularly on community-based studies, are needed to fully determine the impact of the pandemic on the malaria situation.
A cross-sectional study exploring the justification of opportunistic breast cancer screening in Thailand
Authors: Lerttiendamrong Bhoowit , Satapongpeera Lertpong , Vongsaisuwon Mawin 
Published: November 2021

AbstractObjectiveBreast cancer is currently the most common malignant disease in Thailand. The present study aims to evaluate the most beneficial method of breast cancer screening in different breast densities by analyzing the benefits of screening mammography with additional breast ultrasonography classified by breast density.Method49 middle-aged and elderly Bangkokian women who had undergone both mammography and ultrasonography were picked at random for analysis. BI-RADS scores were assigned based on mammography results alone and based on combined mammography and ultrasonography results. Concordance/discordance rates between the 2 radiographic techniques were compared in women stratified based on their breast densities.ResultsAll of our participants were given a score between BIRADS 1 and 3, while over 40% of participants are in the BIRADS 2 category. 60% of subjects with extremely dense breasts benefit from screening mammography with additional breast ultrasonography, while only 50% of samples with heterogeneous density and 34.21% samples with heterogeneous fibroglandular breasts benefit from the extra intervention.ConclusionOur study concludes that women with higher breast density are more likely to benefit from screening using ultrasonography in addition to mammography as opposed to mammography screening alone. We recommend both mammography and ultrasonography for initial breast cancer screening. For follow-up visits, we suggest the screening method in accordance with breast density, using ultrasonography alone for women with high breast densities and mammography for women with heterogeneously dense breasts.
Deficits in planned hospital care for vulnerable adolescents in England during the COVID-19 pandemic: analysis of linked administrative data
Authors: Grath-Lone Louise Mc , Etoori David , Gilbert Ruth , Harron Katie , Woodman Jenny , Blackburn Ruth 
Published: November 2021

AbstractPlanned hospital care (outpatient attendances and planned hospital admissions) was disrupted during the pandemic, but we lack evidence on which groups of young people were most impacted. We aimed to describe differences in planned care for vulnerable adolescents receiving children’s social care (CSC) services or special educational needs (SEN) support during the pandemic, relative to their peers. Using the ECHILD Database (linked de-identified administrative health, education and social care records for all children in England), we examined changes in planned hospital care from 23 March to 31 December 2020 for secondary school pupils in Years 7 to 11 (N=3,030,235). There were large deficits in planned care for adolescents overall, which disproportionately affected the 21% receiving SEN support or CSC services who bore 25% of the outpatient attendance deficit and 37% of the planned admissions deficit. These findings indicate a need for targeted ‘catch-up’ funding and resources, particularly for vulnerable groups.
Mapping SOX9 transcriptional dynamics during multi-lineage differentiation of human mesenchymal stem cells
Authors: Govindaraj Kannan , Khurana Sakshi , Karperien Marcel , Post Janine N. 
Published: November 2021

AbstractThe master transcription factor SOX9 is a key player during chondrocyte differentiation, cartilage development, homeostasis and disease. Modulation of SOX9 and its target gene expression is essential during chondrogenic, osteogenic and adipogenic differentiation of human mesenchymal stem cells (hMSCs). However, lack of sufficient knowledge about the signaling interplay during differentiation remains one of the main reasons preventing successful application of hMSCs in regenerative medicine. We previously showed that Transcription Factor – Fluorescence Recovery After Photobleaching (TF-FRAP) can be used to study SOX9 dynamics at the single cell level. We showed that changes in SOX9 dynamics are linked to its transcriptional activity. Here, we investigated SOX9 dynamics during differentiation of hMSCs into the chondrogenic, osteogenic and adipogenic lineages. We show that there are clusters of cells in hMSCs with distinct SOX9 dynamics, indicating that there are a number of subpopulations present in the heterogeneous hMSCs. SOX9 dynamics data at the single cell resolution revealed novel insights about its activity in these subpopulations (cell types). In addition, the response of SOX9 to differentiation stimuli varied in these subpopulations. Moreover, we identified donor specific differences in the number of cells per cluster in undifferentiated hMSCs, and this correlated to their differentiation potential.
Understanding the mental health experiences of adult men with intellectual disabilities in Singapore
Authors: Ee Jonathan , Lim Jan Mei , Stenfert Kroese Biza , Rose John 
Published: November 2021

Purpose
This study aims to explore the experiences of people with intellectual disabilities in Singapore receiving inpatient mental health treatment. To date, there has not been any research that examines the views and experiences of this population in Singapore. The research examines how the participants view their mental health problems and their experiences of the services they received.

Design/methodology/approach
A qualitative design was chosen to address the research question. Six adult men with intellectual disabilities were recruited from the tertiary hospital and interviewed. The transcripts of these interviews were analysed using interpretative phenomenological analysis.

Findings
Four super-ordinate themes were identified; awareness of mental health problems; yearn for a life outside the ward; interacting with other people and finding purpose.

Originality/value
The participants reported that they struggled with being segregated from their families and communities following an inpatient admission. They were able to report on the emotional difficulties that they experienced and hoped to find employment after their discharge from the hospital. They talked about reconstructing their self-identity and forming friendships to cope with their hospital stay. This research is one of its kind carried out in a non-western society and the findings are discussed in the light of how mental health professionals can best support people with intellectual disabilities during their inpatient treatment.
Semi-analytical finite element method for simulating chemical dissolution-front instability problems in fluid-saturated porous media
Authors: Zhao Chongbin , Hobbs B.E. , Ord Alison 
Published: November 2021

PurposeThe objective of this paper is to develop a semi-analytical finite element method for solving chemical dissolution-front instability problems in fluid-saturated porous media.Design/methodology/approachThe porosity, horizontal and vertical components of the pore-fluid velocity and solute concentration are selected as four fundamental unknown variables for describing chemical dissolution-front instability problems in fluid-saturated porous media. To avoid the use of numerical integration, analytical solutions for the property matrices of a rectangular element are precisely derived in a purely mathematical manner. This means that the proposed finite element method is a kind of semi-analytical method. The column pivot element solver is used to solve the resulting finite element equations of the chemical dissolution-front instability problem.FindingsThe direct use of horizontal and vertical components of the pore-fluid velocity as fundamental unknown variables can improve the accuracy of the related numerical solution. The column pivot element solver is useful for solving the finite element equations of a chemical dissolution-front instability problem. The proposed semi-analytical finite element method can produce highly accurate numerical solutions for simulating chemical dissolution-front instability problems in fluid-saturated porous media.Originality/valueAnalytical solutions for the property matrices of a rectangular element are precisely derived for solving chemical dissolution-front instability problems in fluid-saturated porous media. The proposed semi-analytical finite element method provides a useful way for understanding the underlying dynamic mechanisms of the washing land method involved in the contaminated land remediation.
Bean There: coffee as a vehicle for change
Authors: Thomson Richard , Hofmeyr Katherine , Bowen Amanda 
Published: November 2021

Case overview
At midnight on Thursday, 26 March 2020, the South African government ordered a three-week lockdown in response to the COVID-19 pandemic and subsequently extended this lockdown for a further two weeks until the end of April 2020. Among other measures, businesses not classed as “essential” had to cease operation. This meant that Jonathan Robinson, founder of the Bean There Coffee Company had to close his trendy Cape Town and Milpark coffee shops, as well as the company’s hospitality and corporate business. At the same time, Bean There’s costs increased by 25%, as the rand: dollar exchange rate worsened substantially. A glimmer of hope was that the company was able to continue roasting coffee and supplying its retail clients. Unlike most captains of industry, Robinson was not driven by the bottom line and clamouring shareholders. His corporate strategy was driven by a single, simple purpose: to achieve ethical sustainability aspirations while still running a profitable business. The question for him now, however, was how to ensure that his company could survive in the short term, so that it could achieve these goals in the longer term, and whether he could take this opportunity to think about whether his business was best positioned to achieve these goals when things returned to normal.

Expected learning outcomes
The learning outcomes are as follows: conduct a thorough analysis of a specific company and its industry, including its markets, competitors, and other aspects of the internal and external business environment, using a range of tools, including a Business Model Canvas (BMC), SWOT analysis and PESTLE analysis; analyse and explain the market outlook of a company; identify and analyse a company’s competitors; discuss and explain a detailed implementation plan showing the way forward for a company, considering its current challenges, including integrating a range of conceptual and analytical fields of knowledge to assess a management dilemma, and arrive at a creative and innovative management solution; and be able to present information and defend substantial insights and solutions to a management dilemma in oral and written modes, appropriate in standard for both the academic and business communities to analyse and appreciate.

Complexity academic level
Postgraduate Diploma in Management, MBA, Masters in Management, Executive Education.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 11: Strategy.