bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of COVID-19 on mortality in coastal Kenya: a longitudinal open cohort study
Authors: Otiende M , Nyaguara A , Bottomley C , Walumbe D , Mochamah G , Amadi D , Nyundo C , Kagucia EW , Etyang AO , Adetifa IMO , Brand SPC , Maitha E , Chondo E , Nzomo E , Aman R , Mwangangi M , Amoth P , Kasera K , Ng’ang’a W , Barasa E , Tsofa B , Mwangangi J , Bejon P , Agweyu A , Williams TN , Scott JAG 
Published: October 2022

ABSTRACTBackgroundThere is uncertainty about the mortality impact of the COVID-19 pandemic in Africa because of poor ascertainment of cases and limited national civil vital registration. We analysed excess mortality from 1stJanuary 2020-5thMay 2022 in a Health and Demographic Surveillance Study in Coastal Kenya where the SARS-CoV-2 seroprevalence reached 75% among adults in March 2022 despite vaccine uptake of only 17%.MethodsWe modelled expected mortality in 2020-2022 among a population of 306,000 from baseline surveillance data between 2010-2019. We calculated excess mortality as the ratio of observed/expected deaths in 5 age strata for each month and for each national wave of the pandemic. We estimated cumulative mortality risks as the total number of excess deaths in the pandemic per 100,000 population. We investigated observed deaths using verbal autopsy.FindingWe observed 16,236 deaths among 3,410,800 person years between 1stJanuary 2010 and 5thMay 2022. Across 5 waves of COVID-19 cases during 1st April 2020-16thApril 2022, population excess mortality was 4.1% (95% PI -0.2%, 7.9%). Mortality was elevated among those aged ≥65 years at 14.3% (95% PI 7.4%, 21.6%); excess deaths coincided with wave 2 (wild-type), wave 4 (Delta) and wave 5 (Omicron BA1). Among children aged 1-14 years there was negative excess mortality of -20.3% (95% PI -29.8%, -8.1%). Verbal autopsy data showed a transient reduction in deaths from acute respiratory infections in 2020 at all ages. For comparison with other studies, cumulative excess mortality risk for January 2020-December 2021, age-standardized to the Kenyan population, was 47.5/100,000.InterpretationNet excess mortality during the pandemic was substantially lower in Coastal Kenya than in many high income countries. However, adults, aged ≥65 years, experienced substantial excess mortality suggesting that targeted COVID-19 vaccination of older persons may limit further COVID-19 deaths by protecting the residual pool of naive individuals.FundingWellcome Trust
Recombinant Human Proteoglycan 4 (rhPRG4) Downregulates TNFα-Stimulated NFκB Activity and FAT10 Expression in Human Corneal Epithelial Cells
Authors: Menon Nikhil G , Suhail Yasir , Goyal Ruchi , Du Wenqiang , Tanguay Adam P , Jay Gregory D. , Ghosh Mallika , Kshitiz  , Schmidt Tannin A 
Published: October 2022

AbstractDry Eye Disease (DED) is a complex pathology affecting millions of people with significant impact on quality of life. Corneal inflammation, including via the NFκB pathway, plays a key etiological role in DED. Recombinant human proteoglycan 4 (rhPRG4) has been shown to be a clinically effective treatment for DED that has anti-inflammatory effects in corneal epithelial cells, but the underlying mechanism is still not understood. Our goal was to understand if rhPRG4 affects TNFα-stimulated inflammatory activity in corneal epithelial cells. We treated hTERT-immortalized corneal epithelial (hTCEpi) cells ±TNFα ±rhPRG4 and performed Western blotting on cell lysate and RNA sequencing. Bioinformatics analysis revealed that rhPRG4 had a significant effect on TNFα-mediated inflammation with potential effects on matricellular homeostasis. rhPRG4 reduced activation of key inflammatory pathways and decreased expression of transcripts for key inflammatory cytokines, interferons, interleu-kins, and transcription factors. TNFα treatment significantly increased phosphorylation and nuclear translocation of p65, and rhPRG4 significantly reduced both these effects. RNA sequencing identified FAT10, which has not been studied in the context of DED, as a key pro-inflammatory transcript increased by TNFα and decreased by rhPRG4. These results were confirmed at the protein level. In summary, rhPRG4 is able to downregulate NFκB activity in hTCEpi cells, suggesting a potential biological mechanism by which it may act as a therapeutic for DED.
Is brightfield all you need for mechanism of action prediction?
Authors: Gupta Ankit , Harrison Philip J , Wieslander Håkan , Rietdijk Jonne , Puigvert Jordi Carreras , Georgiev Polina , Wählby Carolina , Spjuth Ola , Sintorn Ida-Maria 
Published: October 2022

AbstractFluorescence staining techniques, such as Cell Painting, together with fluorescence microscopy have proven invaluable for visualizing and quantifying the effects that drugs and other perturbations have on cultured cells. However, fluorescence microscopy is expensive, time-consuming, and labor-intensive, and the stains applied can be cytotoxic, interfering with the activity under study. The simplest form of microscopy, brightfield microscopy, lacks these downsides, but the images produced have low contrast and the cellular compartments are difficult to discern. Nevertheless, by harnessing deep learning, these brightfield images may still be sufficient for various predictive purposes. In this study, we compared the predictive performance of models trained on fluorescence images to those trained on brightfield images for predicting the mechanism of action (MoA) of different drugs. We also extracted CellProfiler features from the fluorescence images and used them to benchmark the performance. Overall, we found comparable and correlated predictive performance for the two imaging modalities. This is promising for future studies of MoAs in time-lapse experiments.
Human serum induces daptomycin tolerance inEnterococcus faecalisand viridans group streptococci
Authors: Tickle Alicia R. H. , Ledger Elizabeth V. K. , Edwards Andrew M. 
Published: October 2022

AbstractDaptomycin is a membrane-targeting lipopeptide antibiotic used in the treatment of infective endocarditis caused by multidrug-resistant Gram-positive bacteria such asStaphylococcus aureus, enterococci and viridans group streptococci. Despite demonstrating excellentin vitroactivity and a low prevalence of resistant isolates, treatment failure is a significant concern, particularly for enterococcal infection. We have shown recently that human serum triggers daptomycin tolerance inS. aureus, but it was not clear if a similar phenotype occurred in other major infective endocarditis pathogens. We found thatEnterococcus faecalis, Streptococcus gordoniiorStreptococcus mutansgrown under standard laboratory conditions were efficiently killed by daptomycin, whereas bacteria pre-incubated in human serum survived exposure to the antibiotic, with >99% cells remaining viable. Incubation of enterococci or streptococci in serum led to peptidoglycan accumulation, as shown by increased incorporation of the fluorescent D-amino analogue HADA. Inhibition of peptidoglycan accumulation using the antibiotic fosfomycin resulted in a >10-fold reduction in serum-induced daptomycin tolerance, demonstrating the important contribution of the cell wall to the phenotype. We also identified a small contribution to daptomycin tolerance inE. faecalisfrom cardiolipin synthases, although this may reflect the inherent susceptibility of cardiolipin-deficient mutants. In summary, serum-induced daptomycin tolerance is a consistent phenomenon between Gram-positive infective endocarditis pathogens, but it may be mitigated using currently available antibiotic combination therapy.
Matrix Softening Controls Stretch-Induced Cellular Memory and Fibroblast Activation
Authors: Hong Yuan , Peng Xiangjun , Yu Haomin , Jafari Mohammad , Shakiba Delaram , Huang Yuxuan , Qu Chengqing , Melika Ermia E. , Tawadros Andrew K. , Mujahid Aliza , Sandler Jacob , Pryse Kenneth M. , Sacks Justin M. , Elson Elliot L. , Genin Guy M. , Alisafaei Farid 
Published: October 2022

AbstractMechanical stretching of living tissues can activate long-lived changes in tissue cells such as fibroblasts, increasing their contractility and initiating phenotypic transformations. Increased mechanical stimulus typically leads to monotonically increasing activation of fibroblasts cultured in 2D, but activation levels are difficult to predict for cells in 3D fibrous tissues, leading to variable outcomes in procedures such as skin grafting. Here we report that the source of this variation is cell-extracellular matrix (ECM) interactions and their variation with the duration and magnitude of applied stretch, and present a model that can predict the degree to which stretch will either increase or decrease long-term activation levels of fibroblasts cultured within a stretched, three-dimensional collagen matrix. Combining experimental and mathematical approaches across multiple scales, we show that the viscoplasticity of the ECM regulates this nonmonotonic, long-term cell activation. Results demonstrate that feedback between cell and ECM determines how cells retain memory of mechanical stretch.
An optimized Tet-On system for conditional control of gene expression in sea urchins
Authors: Khor Jian Ming , Ettensohn Charles A. 
Published: October 2022

AbstractSea urchins and other echinoderms are important experimental models for studying developmental processes. The lack of approaches for conditional gene perturbation, however, has made it challenging to investigate the late developmental functions of genes that have essential roles during early embryogenesis and genes that have diverse functions in multiple tissues. The doxycycline-controlled Tet-On system is a widely used molecular tool for temporally and spatially regulated transgene expression. Here, we optimized the Tet-On system to conditionally induce gene expression in sea urchin embryos. Using this approach, we explored the roles the MAPK signaling plays in skeletogenesis by expressing genes that perturb the pathway specifically in primary mesenchyme cells (PMCs) during later stages of development. We demonstrated the wide utility of the Tet-On system by applying it to a second sea urchin species and in cell types other than the PMCs. Our work provides a robust and flexible platform for the spatio-temporal regulation of gene expression in sea urchins, which will considerably enhance the utility of this prominent model system.
HDAC8-mediated inhibition of EP300 drives a neural crest-like transcriptional state that increases melanoma brain metastasis
Authors: Emmons Michael F. , Bennett Richard L. , Riva Alberto , Zhang Chao , Macaulay Robert , Dupéré-Richér Daphne , Fang Bin , Seto Edward , Koomen John M. , Li Jiannong , Chen Y. Ann , Forsyth Peter A. , Licht Jonathan D. , Smalley Keiran S.M. 
Published: October 2022

AbstractMelanomas are heterogeneous and adopt multiple transcriptional states that can confer an invasive phenotype and resistance to therapy. Little is known about the epigenetic drivers of these cell states, limiting our ability to regulate melanoma heterogeneity and tumor progression. Here we identify stress-induced HDAC8 activity as the driver of a neural crest stem cell (NCSC)-like transcriptional state that increased the formation of melanoma brain metastases (MBM). Exposure of melanocytes and melanoma cells to multiple different stresses led to HDAC8 activation, a switch to a NCSC gene expression signature and the adoption of an amoeboid, invasive phenotype. This cell state enhanced the survival of melanoma cells under shear stress conditions and increased the formation of metastases in the brain. scRNA-seq analyses showed that HDAC8 expression was correlated with the NCSC cell state in clinical MBM specimens. ATAC-Seq and ChIP-Seq analysis showed HDAC8 to alter chromatin structure by increasing H3K27ac and accessibility at c-Jun binding sites without changing global histone acetylation. The increased accessibility of Jun binding sites was paralleled by decreased H3K27ac and accessibility at MITF binding sites and loss of melanoma-lineage gene expression. Mass spectrometry-based acetylomics demonstrated that HDAC8 deacetylated the histone acetyltransferase (HAT) EP300 leading to its enzymatic inactivation. This, in turn, led to an increased binding of EP300 to Jun-transcriptional sites and decreased binding to MITF-transcriptional sites. Increased expression of EP300 decreased invasion and increased the sensitivity of melanoma cells to multiple stresses while inhibition of EP300 function increased invasion and resistance to stress. We identified HDAC8 as a novel mediator of transcriptional co-factor inactivation and chromatin accessibility that increases MBM development.
Coil shape defects prediction algorithm for hot strip rolling based on Siamese semi-supervised DAE-CNN model
Authors: Jing Fengwei , Zhang Mengyang , Li Jie , Xu Guozheng , Wang Jing 
Published: October 2022

Purpose
Coil shape quality is the external representation of strip product quality, and it is also a direct reflection of strip production process level. This paper aims to predict the coil shape results in advance based on the real-time data through the designed algorithm.

Design/methodology/approach
Aiming at the strip production scale and coil shape application requirements, this paper proposes a strip coil shape defects prediction algorithm based on Siamese semi-supervised denoising auto-encoder (DAE)-convolutional neural networks. The prediction algorithm first reconstructs the information eigenvectors using DAE, then combines the convolutional neural networks and skip connection to further process the eigenvectors and finally compares the eigenvectors with the full connect neural network and predicts the strip coil shape condition.

Findings
The performance of the model is further verified by using the coil shape data of a steel mill, and the results show that the overall prediction accuracy, recall rate and F-measure of the model are significantly better than other commonly used classification models, with each index exceeding 88%. In addition, the prediction results of the model for different steel grades strip coil shape are also very stable, and the model has strong generalization ability.

Originality/value
This research provides technical support for the adjustment and optimization of strip coil shape process based on the data-driven level, which helps to improve the production quality and intelligence level of hot strip continuous rolling.
Stifled from the start: biased allocation of developmental opportunities and the underrepresentation of lesbian women and gay men in leadership
Authors: Webster Jennica R. , Adams Gary A. 
Published: October 2022

PurposeThe goal of this study was to help explain the underrepresentation of lesbian women and gay men (LG) in senior leadership positions by examining bias in the allocation of developmental opportunities (sponsorship/coaching and challenging work assignments). It further sought to test stigma-by-association as one reason for the biased allocation of developmental opportunities.Design/methodology/approachAn online experimental vignette study (N = 273) using a 2 (target gender: male vs female) by 2 (sexual orientation: LG vs heterosexual) design was conducted.FindingsLG workers were less likely to be allocated developmental opportunities than heterosexual workers overall and relative to their same-sex heterosexual counterparts. Further, lesbian women were least likely to be allocated developmental opportunities. These effects also operated indirectly via participants concerns about stigma-by-association.Originality/valueSexual orientation and gender identity minority workers remain underrepresented in senior leadership positions and oftentimes despite having better objective qualifications. Research has begun examining bias in leader selection. This study, however, directs attention to the biased allocation of developmental opportunities which make one competitive for senior leadership positions and occur prior to leader selection. In doing so, the authors provide a baseline understanding of an important reason why LG might be underrepresented in leadership positions.
Investor attention, analysts coverage and idiosyncratic volatility puzzle: based on behavioral perspective
Authors: Tian Xinmin , Zhang Zhiqiang , Zhang Cheng , Gao Mingyu 
Published: October 2022

PurposeConsidering the role of analysts in disseminating information, the paper explains the idiosyncratic volatility puzzle of China's stock market. As the largest developing country, China's research can provide meaningful reference for the research of financial markets in other new countries.Design/methodology/approachFrom the perspective of behavior, establishing a direct link between individual investor attention and stock price overvaluation.FindingsThe authors find that there is a significant idiosyncratic volatility puzzle in China's stock market. Due to the role of mispricing, individual investor attention significantly enhances the idiosyncratic volatility effect, that is, as individual investor attention increases, the greater the idiosyncratic volatility, the lower the expected return. Attention can explain the idiosyncratic volatility puzzle in China's stock market. In addition, due to the role of information production and dissemination, securities analysts can reduce the degree of market information asymmetry and enhance the transparency of market information.Originality/valueChina is the second largest economy in the world, and few scholars analyze it from the perspective of investors' attention. The authors believe this paper has the potential in contributing to the academia.
Profit, cash flow, and leverage: the case of ASEAN stock market performance during the COVID-19 pandemic
Authors: Abbas Yulianti , Nainggolan Yunieta Anny 
Published: October 2022

PurposeThe coronavirus disease 2019 (COVID-19) outbreak in the first quarter of 2020 has caused a severe decline in stock markets worldwide. While prior studies in developed markets found that workplace closure can negatively impact the capital market (e.g. Ozili and Arun, 2020), lesser is known about how it impacts emerging capital markets, which may have different characteristics and behaviour (Harjoto et al., 2021). Hence, this study seeks to uncover stock performance around workplace closure dates of firms incorporated in ASEAN countries and investigates the role of accounting fundamentals in mitigating workplace closure policy's effects on stock performances.Design/methodology/approachUsing an event study methodology, the authors measure the cumulative abnormal returns (CARs) around workplace closure dates. The authors then use cross-sectional analysis to analyse whether the accounting fundamentals, specifically profitability, cash flow, and leverage, are associated with the CAR. This cross-sectional study involves 1,720 firms that are incorporated in the ASEAN countries.FindingsThis analysis indicates that, on average, ASEAN capital markets react negatively to workplace closure policies. The authors then find that the CARs around workplace closure dates are positively associated with the current ratios and are negatively associated with long-term debt ratios. This study’s results thus indicate that firms with a higher liquidity and a higher solvency experience a less adverse impact of the COVID-19 pandemic than other firms. The authors also find that the associations are more robust for (1) firms in industries more affected by COVID-19 and (2) firms located in countries with more severe cases. Additionally, contrary to this study’s expectation, the authors do not find meaningful associations between CARs around workplace closure dates and firms' cash flow from operation and profit respectively. This study’s results suggest that investors view prior performances related to firms' ability to generate operating cash flow and profit as less relevant to measure firm performance around the workplace closure event.Research limitations/implicationsThis study’s results contribute to studies examining fundamental accounting roles during the COVID-19 era, specifically in emerging economies. The findings are critical for investors in understanding the company fundamentals associated with stock price performance in emerging markets during the recent health-related crisis.Originality/valueMost studies analysing cross-sectional differences in stock returns during the COVID-19 era focus on industry-level differences and use observations from developed markets (Sinagl, 2020; Ramelli and Wagner, 2020). Studies using firm-level analysis in emerging markets are still limited. The authors expand prior studies by using firm-level analysis that spans six countries in ASEAN.
Digital transformation in a cross-laminated timber business network
Authors: Hamalainen Mervi , Salmi Asta 
Published: October 2022

Purpose
The purpose of this paper is to investigate two current transformation processes in the construction industry: the adoption of a novel material, cross-laminated timber (CLT), and the enhancement of digital transformation. This paper depicts the actors and interaction in the business network that is emerging around CLT construction and, in particular, how digital transformation (that is, the deployment of Construction 4.0 solutions) occurs in this business network.

Design/methodology/approach
Digital transformation is a relatively new phenomenon in CLT construction, and the authors, therefore, adopt a qualitative inductive research approach and rely on semi-structured interviews.

Findings
The findings of this paper suggest that it is critical for actors to adopt an interorganizational perspective in CLT construction, instead of only focusing on internal operations. An interorganizational perspective supports successful CLT construction, as well as the deployment of Construction 4.0 solutions. This will bring about the benefits of digital transformation in the construction industry.

Research limitations/implications
This paper investigates the network created around CLT construction in Finland but more generally illustrates the change toward Construction 4.0 solutions.

Practical implications
For managers, this paper explicates the importance of networking, instead of focusing on the internal development of the company, when adopting novel solutions emerging from both construction and information technology-related advancements.

Originality/value
Stability and traditions are characteristic of the construction industry. New technical solutions and materials, together with calls for sustainability, have challenged the traditional ways of constructing, and for example, the development of CLT construction has led to an emergence of new business networks. This material-related process and the ongoing digital transformation of business form an interesting context for an empirical-based analysis of changing interaction and networks. This paper gives the first insights into how digital transformation can benefit the evolution of the network.