bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing Light-Sheet Fluorescence Microscopy Illumination Beams through Deep Design Optimization
Authors: Li Chen , Rai Mani Ratnam , Cai Yuheng , Ghashghaei H. Troy , Greenbaum Alon 
Published: December 2023

AbstractLight sheet fluorescence microscopy (LSFM) provides the benefit of optical sectioning coupled with rapid acquisition times for imaging of tissue-cleared specimen. This allows for high-resolution 3D imaging of large tissue volumes. Inherently to LSFM, the quality of the imaging heavily relies on the characteristics of the illumination beam, with the notion that the illumination beam only illuminates a thin section that is being imaged. Therefore, substantial efforts are dedicated to identifying slender, non-diffracting beam profiles that can yield uniform and high-contrast images. An ongoing debate concerns the employment of the most optimal illumination beam; Gaussian, Bessel, Airy patterns and/or others. Comparisons among different beam profiles is challenging as their optimization objective is often different. Given that our large imaging datasets (∼0.5TB images per sample) is already analyzed using deep learning models, we envisioned a different approach to this problem by hypothesizing that we can tailor the illumination beam to boost the deep learning models performance. We achieve this by integrating the physical LSFM illumination model after passing through a variable phase mask into the training of a cell detection network. Here we report that the joint optimization continuously updates the phase mask, improving the image quality for better cell detection. Our method’s efficacy is demonstrated through both simulations and experiments, revealing substantial enhancements in imaging quality compared to traditional Gaussian light sheet. We offer valuable insights for designing microscopy systems through a computational approach that exhibits significant potential for advancing optics design that relies on deep learning models for analysis of imaging datasets.
Accurate long-read transcript discovery and quantification at single-cell resolution with Isosceles
Authors: Kabza Michal , Ritter Alexander , Byrne Ashley , Sereti Kostianna , Le Daniel , Stephenson William , Sterne-Weiler Timothy 
Published: December 2023

AbstractAccurate detection and quantification of mRNA isoforms from nanopore long-read sequencing remains challenged by technical noise, particularly in single cells. To address this, we introduce Isosceles, a computational toolkit that outperforms other methods in isoform detection sensitivity and quantification accuracy across single-cell, pseudo-bulk and bulk resolution levels, as demonstrated using synthetic and biologically-derived datasets. Isosceles improves the fidelity of single-cell transcriptome quantification at the isoform-level, and enables flexible downstream analysis. As a case study, we apply Isosceles, uncovering coordinated splicing within and between neuronal differentiation lineages. Isosceles is suitable to be applied in diverse biological systems, facilitating studies of cellular heterogeneity across biomedical research applications.
Increased levels of circulating methylglyoxal have no consequence for cerebral microvascular integrity and cognitive function in young healthy mice
Authors: Berends Eline , Vangrieken Philippe , Amiri Naima , van de Waarenburg Marjo P.H. , Scheijen Jean L.J.M. , Hermes Denise J.H.P. , van Oostenbrugge Robert J. , Schalkwijk Casper G. , Foulquier Sébastien 
Published: December 2023

AbstractDiabetes and other age-related diseases are associated with an increased risk of cognitive impairment, but the underlying mechanisms remain poorly understood. Methylglyoxal (MGO), a by-product of glycolysis and a major precursor in the formation of advanced glycation end- products (AGEs), is increased in individuals with diabetes and other age-related diseases, and is associated with microvascular dysfunction. We now investigated whether increased levels of circulating MGO can lead to cerebral microvascular dysfunction, blood brain barrier (BBB) dysfunction, and cognitive impairment. Mice were supplemented or not with 50 mM MGO in drinking water for 13 weeks. Plasma and cortical MGO and MGO-derived AGEs were measured with UPLC-MS/MS. Peripheral and cerebral microvascular integrity and inflammation were investigated. Cerebral blood flow and neurovascular coupling were investigated with laser speckle contrast imaging, and cognitive tests were performed. We found a 2-fold increase in plasma MGO and an increase in MGO-derived AGEs in plasma and cortex. Increased plasma MGO did not lead to cerebral microvascular dysfunction, inflammation, nor cognitive decline. This study shows that increased concentrations of plasma MGO are not associated with cerebral microvascular dysfunction and cognitive impairment in healthy mice. Future research should focus on the role of endogenously formed MGO in cognitive impairment.
Interpretable Machine Learning Decodes Soil Microbiome’s Response to Drought Stress
Authors: Hagen Michelle , Dass Rupashree , Westhues Cathy , Blom Jochen , Schultheiss Sebastian J , Patz Sascha 
Published: December 2023

AbstractBackgroundExtreme weather events induced by climate change, particularly droughts, have detrimental consequences for crop yields and food security. Concurrently, these conditions provoke substantial changes in the soil metagenome and affect plant health. Early recognition of soil affected by drought enables farmers to implement appropriate agricultural management practices. In this context, interpretable Machine Learning holds immense potential for drought stress classification in the soil metagenome based on marker taxa.ResultsThis study demonstrates that the metagenomic approach of Differential Abundance Analysis methods and Machine Learning-based Shapley Additive Explanation values provide similar information. They exhibit their potential as complementary approaches for identifying marker taxa and investigating their enrichment or depletion under drought stress in grass lineages. Additionally, the Random Forest Classifier trained on a diverse range of relative abundance data from the soil metagenome of various plant species achieves a high accuracy of 92.3 % at the genus rank for drought stress prediction. It demonstrates its generalization capacity for the lineages tested.ConclusionsIn the detection of drought stress in the soil metagenome, this study emphasizes the potential of an optimized and generalized location-based ML classifier. By identifying marker taxa, this approach holds promising implications for microbe-assisted plant breeding programs and contributes to the development of sustainable agriculture practices. These findings are crucial for preserving global food security in the face of climate change.
Transfer of disulfide bond formation modules via yeast artificial chromosomes promotes the expression of heterologous proteins inKluyveromyces marxianus
Authors: Wu Pingping , Mo Wenjuan , Tian Tian , Song Kunfeng , Lyu Yilin , Ren Haiyan , Zhou Jungang , Yu Yao , Lu Hong 
Published: December 2023

AbstractKluyveromyces marxianusis a food-safe yeast with great potential for producing heterologous proteins. Improving the yield inK. marxianusremains a challenge, while incorporating large-scale functional modules poses a technical obstacle in engineering. To address these issues, linear and circular yeast artificial chromosomes ofK. marxianus(KmYACs) were constructed and loaded with disulfide bond formation modules fromPichia pastorisorK. marxianus. These modules contained up to 7 genes with a maximum size of 15 kb. KmYACs carried telomeres either fromK. marxianusorTetrahymena. KmYACs were transferred successfully intoK. marxianusand stably propagated without affecting the normal growth of the host, regardless of the type of telomeres and configurations of KmYACs. KmYACs increased the overall expressions of disulfide bond formation genes and significantly enhanced the yield of various heterologous proteins. In high-density fermentation, the use of KmYACs resulted in a glucoamylase yield of 16.8 g/L, the highest reported level to date inK. marxianus. Transcriptomic and metabolomic analysis of cells containing KmYACs suggested increased FAD biosynthesis, enhanced flux entering the TCA cycle and a preferred demand for lysine and arginine as features of cells overexpressing heterologous proteins. Consistently, supplementing lysine or arginine further improved the yield. Therefore, KmYAC provides a powerful platform for manipulating large modules with enormous potential for industrial applications and fundamental research. Transferring the disulfide bond formation module via YACs proves to be an efficient strategy for improving the yield of heterologous proteins, and this strategy may be applied to optimize other microbial cell factories.Impact StatementIn this study, yeast artificial chromosomes ofK. marxianus(KmYACs) were constructed and successfully incorporating modules for large-scale disulfide bond formation. KmYACs were stably propagated inK. marxianuswithout compromising the normal growth of the host, irrespective of the selection of telomeres (eitherTetrahymenaorK. marxianus) and configuration (either linear or circular). KmYACs notably enhanced the expressions of various heterologous proteins, with further yield improvement by supplementing lysine or arginine in the medium. Our findings affirm KmYAC as a robust and versatile platform for transferring large-scale function modules, demonstrating immense potential for both industrial applications and fundamental research.
Histone N-tails modulate sequence-specific positioning of nucleosomes
Authors: Nikitina Tatiana , Guiblet Wilfried M. , Cui Feng , Zhurkin Victor B. 
Published: December 2023

AbstractThe precise mechanisms governing sequence-dependent positioning of nucleosomes on DNA remain unknown in detail. Existing algorithms, taking into account the sequence-dependent deformability of DNA and its interactions with the histone globular domains, predict rotational setting of only 65% of human nucleosomes mappedin vivo. To uncover novel factors responsible for the nucleosome positioning, we analyzed potential involvement of the histone N-tails in this process. To this aim, we reconstituted the H2A/H4 N-tailless nucleosomes on human BRCA1 DNA (∼100 kb) and compared their positions and sequences with those of the wild-type nucleosomes. In the case of H2A tailless nucleosomes, the AT content of DNA sequences is changed locally at superhelical location (SHL) ±4, while maintaining the same rotational setting as their wild-type counterparts. Conversely, the H4 tailless nucleosomes display widespread changes of the AT content near SHL ±1 and SHL ±2, where the H4 N-tails interact with DNA. Furthermore, a substantial number of H4 tailless nucleosomes exhibit rotational setting opposite to that of the wild-type nucleosomes. Thus, our findings strongly suggest that the histone N-tails are operative in selection of nucleosome positions, which may have wide-ranging implications for epigenetic modulation of chromatin states.
TNF-alpha promotes cilia elongation via Mixed Lineage Kinases signaling
Authors: Kumari Amrita , Caliz Amada , Kant Shashi , Vertii Anastassiia 
Published: December 2023

ABSTRACTThe primary cilium is characteristic of most of non-immune cells and acts as an environmental signal transduction sensor. The defects in primary cilium have profound consequences on the developmental program, including the maturation of retinal epithelium. The ciliary length is tightly regulated during ciliogenesis. Additionally, many features of ciliogenesis are shared with an immune synapse formation. While the interaction between the cells within an immune synapse is well-characterized, the impact of inflammatory stresses on ciliogenesis in non-immune cells remains elusive. The current study investigates the outcome of inflammatory stimuli for the primary cilium in human retinal epithelial cells. Here, we report that the exposure of retinal epithelium cells to pro-inflammatory cytokine TNF-alpha elongates cilia in a Mixed-Lineage Kinase (MLK) - dependent manner. In contrast, febrile condition-mimicking heat stress dramatically reduced the number of ciliated cells regardless of TNF-alpha exposure, suggesting distinct but rapid effects of inflammatory stresses on ciliogenesis.
High-throughput ML-guided design of diverse single-domain antibodies against SARS-CoV-2
Authors: Angermueller Christof , Mariet Zelda , Jester Ben , Engelhart Emily , Emerson Ryan , Alipanahi Babak , Lin Charles , Shikany Colleen , Guion Daniel , Nelson Joel , Kelley Mary , McMurray Margot , Shaffer Parker , Cordray Cameron , Halabiya Samer , Mccaw Zachary , Struyvenberg Sarah , Aggarwal Kanchan , Ertel Stacey , Martinez Anissa , Ozarkar Snehal , Hager Kevin , Frumkin Mike , Roberts Jim , Lopez Randolph , Younger David , Colwell Lucy J. 
Published: December 2023

AbstractTreating rapidly evolving pathogenic diseases such as COVID-19 requires a therapeutic approach that accommodates the emergence of viral variants over time. Our machine learning (ML)-guided sequence design platform combines high-throughput experiments with ML to generate highly diverse single-domain antibodies (VHHs) that bind and neutralize SARS-CoV-1 and SARS-CoV-2. Crucially, the model, trained using binding data against early SARS-CoV variants, accurately captures the relationship between VHH sequence and binding activity across a broad swathe of sequence space. We discover ML-designed VHHs that exhibit considerable cross-reactivity and successfully neutralize targets not seen during training, including the Delta and Omicron BA.1 variants of SARS-CoV-2. Our ML-designed VHHs include thousands of variants 4-15 mutations from the parent sequence with significantly improved activity, demonstrating that ML-guided sequence design can successfully navigate vast regions of sequence space to unlock and future-proof potential therapeutics against rapidly evolving pathogens.
Queen Ndlovu: opening the throttle on her drone business
Authors: Urban Boris , Townsend Stephanie Althea 
Published: December 2023

Learning outcomes
After completion of the case study, students will be able to evaluate the journey of launching a business in an emerging market context and judge how opportunities and challenges can be navigated to build sustainable enterprises; assess the relevance of individual attributes and process skills that are necessary for entrepreneurial agency to transform social structures through entrepreneurial action; formulate an argument highlighting the role of the entrepreneurial ecosystem in growing a competitive business in an emerging market context; make an informed decision and critique how accelerators and incubators affect the development of ideas and access to finance in South Africa; and propose various strategic options available for technology entrepreneurs, considering the challenges they face in emerging economies.

Case overview/synopsis
In April 2023, Queen Ndlovu, CEO and founder of QP Drone Tech, a provider of drone business solutions, was considering options to fulfil her original dream of manufacturing drones in South Africa. She had encountered obstacles to achieving the same in 2019, and had decided to focus on providing commercial drone consulting services. However, her dream had not extinguished, and in 2022, she decided to restart her efforts. She found practical support from The Innovation Hub, an incubator that was supporting her business, which enabled her to enhance the prototype of her drone. She then had to think about how she would manufacture drones locally by ensuring she had access to production infrastructure, funding, partners and customers. Would she be able to gain a competitive advantage that would differentiate her from competitors? Or should she reconsider whether she should be manufacturing in the first place, as there are risks and benefits for smaller businesses in this regard.

Complexity academic level
This case is intended for discussion in postgraduate diploma in business and Master of Business Administration courses.

Supplementary material
Teaching notes are available for educators only.

Subject code
CSS 3: Entrepreneurship.
Understanding the determinants of gifting and social sharing in live streaming: a dual-attachment perspective
Authors: Zhang Yan , Sun Yongqiang , Wang Nan 
Published: December 2023

PurposeThis study aims to explore the determinants of viewers’ gifting and social sharing behaviours in online streaming from a dual-attachment perspective and to explain how live streaming fosters attachment through a social interaction aspect.Design/methodology/approachThis study conducted an online survey with 316 valid responses to test the research model. The structural equation modelling approach was applied to assess both the measurement and structural models.FindingsThe results show that both bond-based and identity-based attachments promote gifting and social sharing behaviours. Participation and cognitive communion motivate viewers to establish bond-based attachment, while group interaction among viewer crowds encourages viewers to create identity-based attachment. In addition, group interaction can moderate the relationship between participation and bond-based attachment.Originality/valueThis study is one of the earliest attempts to highlight the significance of viewer crowd and viewer-viewer interaction in promoting viewers’ behaviours in live streaming context. This study also indicates that viewer-viewer interaction can moderate the impact of viewer–streamer interaction, which is among the first to investigate the interaction effects of viewer-viewer interaction and viewer–streamer interaction.
Are Malaysian undergraduates prepared to study online if another MCO exists?
Authors: Soekarno Megawati , Abd Jalil Mohamad Isa , Lada Suddin , Samsu Siti Hajar , Mokthar Mohammad Zulfakhairi , Shariff Abd Kadir Shariff Umar 
Published: December 2023

Purpose The world after the pandemic of Covid-19 is looking at a different environment in teaching and learning and primarily being influenced by general online learning readiness. Perception towards the measurement of online learning readiness would also need to change. This study seeks to determine whether Malaysian undergraduate students are ready to study online if the Movement Control Order (MCO) is reimposed.Design/methodology/approach Using an online poll, this study analysed 299 undergraduate students from Malaysia's public and private universities. The collected data were then analysed using SmartPLS software to test the measurement model and structural equation modelling.Findings The findings of this study indicate that computer self-efficacy and self-directed learning have a substantially positive link with online learning preparedness among Malaysian undergraduate students.Research limitations/implications Findings in this study indicate that universities should draw comprehensive plans to enhance students' readiness in terms of indicators such as technology usage, technology availability, computer and internet efficacy, self-directed learning and attitude. One of the aspects that require change is online communication self-efficacy. Thus, there is a need for improvement, or this would affect undergraduates adversely, especially in the event of future MCO.Originality/value The originality of this article lies in the time frame this study was conducted, where cases of coronavirus infection are seen to increase around the world and there is a possibility that movement restrictions will be re-enforced. The findings in this study are expected to give insight to the government in the effort of the national higher education plan. By not undervaluing previous research models, this research model should give a new perspective to the academic literature on online learning among undergraduate students.
Joint maintenance planning and production scheduling optimization model for green environment
Authors: Attia Ahmed M. , Alatwi Ahmad O. , Al Hanbali Ahmad , Alsawafy Omar G. 
Published: December 2023

PurposeThis research integrates maintenance planning and production scheduling from a green perspective to reduce the carbon footprint.Design/methodology/approachA mixed-integer nonlinear programming (MINLP) model is developed to study the relation between production makespan, energy consumption, maintenance actions and footprint, i.e. service level and sustainability measures. The speed scaling technique is used to control energy consumption, the capping policy is used to control CO2 footprint and preventive maintenance (PM) is used to keep the machine working in healthy conditions.FindingsIt was found that ignoring maintenance activities increases the schedule makespan by more than 21.80%, the total maintenance time required to keep the machine healthy by up to 75.33% and the CO2 footprint by 15%.Research limitations/implicationsThe proposed optimization model can simultaneously be used for maintenance planning, job scheduling and footprint minimization. Furthermore, it can be extended to consider other maintenance activities and production configurations, e.g. flow shop or job shop scheduling.Practical implicationsMaintenance planning, production scheduling and greenhouse gas (GHG) emissions are intertwined in the industry. The proposed model enhances the performance of the maintenance and production systems. Furthermore, it shows the value of conducting maintenance activities on the machine's availability and CO2 footprint.Originality/valueThis work contributes to the literature by combining maintenance planning, single-machine scheduling and environmental aspects in an integrated MINLP model. In addition, the model considers several practical features, such as machine-aging rate, speed scaling technique to control emissions, minimal repair (MR) and PM.
Clinical trial: Clinical and endoscopic outcomes with ustekinumab in patients with Crohn's disease: Results from the long‐term extension period of STARDUST
Authors: Peyrin‐Biroulet Laurent , Vermeire Séverine , D'Haens Geert , Panés Julian , Dignass Axel , Magro Fernando , Nazar Maciej , Le Bars Manuela , Lahaye Marjolein , Ni Lioudmila , Bravatà Ivana , Lavie Frederic , Daperno Marco , Lukáš Milan , Armuzzi Alessandro , Löwenberg Mark , Gaya Daniel R. , Danese Silvio 
Published: December 2023

SummaryBackgroundSTARDUST, a phase 3b randomised trial, compared ustekinumab therapeutic strategies in patients with Crohn's disease (CD) using early endoscopic assessment and treat‐to‐target (T2T) versus standard of care (SoC).AimTo assess the efficacy of ustekinumab extended treatment in a long‐term extension (LTE) of up to 104 weeks with dosing adapted according to clinical, biomarker and endoscopy outcomes.MethodsAdults with moderately‐to‐severely active CD received intravenous ustekinumab approximating 6 mg/kg at Week 0 and subcutaneous ustekinumab 90 mg at Week 8. At Week 16, 440 ≥70‐point responders were randomised to T2T or SoC and 323 entered the LTE. At Week 48, a unified, protocol‐defined ustekinumab dose frequency escalation/de‐escalation was applied based on achieving endoscopic remission and corticosteroid‐free clinical remission. Achieving corticosteroid‐free clinical remission and biomarker remission at consecutive visits determined ustekinumab dosing frequency. Dichotomous variables were analysed using non‐responder imputation.ResultsAmong patients who entered the LTE, 7.7%, 48.6% and 43.7% received doses every 4, 8 and 12 weeks, respectively. Ustekinumab dose frequency was escalated in 23.5% and de‐escalated in 19.7%. Endoscopic response and remission rates were 28.9% and 10.73% (all randomised) and 39.3% and 14.6% (patients entering the LTE), respectively, at Week 104. Clinical remissiona rates at week 104 were 50.2% (all randomised) and 68.4% (patients entering the LTE). There were no new safety signals.ConclusionSTARDUST LTE is the first interventional ustekinumab efficacy study to show a favourable benefit–risk profile with preservation of clinical and endoscopic outcomes through Week 104 using flexible, algorithm‐driven dose adjustment including de‐escalation.