bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin structure and context-dependent sequence features control prime editing efficiency
Authors: Kim Somang , Yuan Jimmy B. , Woods Wendy S. , Newton Destry A. , Perez-Pinera Pablo , Song Jun S. 
Published: April 2023

AbstractPrime editor (PE) is a highly versatile CRISPR-Cas9 genome editing technique. The current constructs, however, have variable efficiency and may require laborious experimental optimization. This study presents statistical models for learning the salient epigenomic and sequence features of target sites modulating the editing efficiency and provides guidelines for designing optimal PEs. We found that both regional constitutive heterochromatin and local nucleosome occlusion of target sites impede editing, while position-specific G/C nucleotides in the primer binding site (PBS) and reverse transcription (RT) template regions of PE guide-RNA (pegRNA) yield high editing efficiency, especially for short PBS designs. The presence of G/C nucleotides was most critical immediately 5’ to the protospacer adjacent motif (PAM) site for all designs. The effects of different last templated nucleotides were quantified and seen to depend on both PBS and RT template lengths. Our models found AGG to be the preferred PAM and detected a guanine nucleotide four bases downstream of PAM to facilitate editing, suggesting a hitherto-unrecognized interaction with Cas9. A neural network interpretation method based on nonextensive statistical mechanics further revealed multi-nucleotide preferences, indicating dependency among several bases across pegRNA. Our work clarifies previous conflicting observations and uncovers context-dependent features important for optimizing PE designs.
Molecular, metabolic and functional CD4 T cell paralysis impedes tumor control
Authors: Guo Mengdi , Abd-Rabbo Diala , Bertol Bruna , Carew Madeleine , Lukhele Sabelo , Snell Laura M , Xu Wenxi , Boukhaled Giselle M , Elsaesser Heidi , Halaby Marie jo , Hirano Naoto , McGaha Tracy L , Brooks David G 
Published: April 2023

ABSTRACTCD4 T cells are important effectors of anti-tumor immunity, yet the regulation of CD4 tumor-specific T (TTS) cells during cancer development is still unclear. We demonstrate that CD4 TTScells are initially primed in the tumor draining lymph node and begin to divide following tumor initiation. Distinct from CD8 TTScells and previously defined exhaustion programs, CD4 TTScell proliferation is rapidly frozen in place and differentiation stunted by a functional interplay of T regulatory cells and both intrinsic and extrinsic CTLA4 signaling. Together these mechanisms paralyze CD4 TTScell differentiation, redirecting metabolic and cytokine production circuits, and reducing CD4 TTScell accumulation in the tumor. Paralysis is actively maintained throughout cancer progression and CD4 TTScells rapidly resume proliferation and functional differentiation when both suppressive reactions are alleviated. Strikingly, Treg depletion alone reciprocally induced CD4 TTScells to themselves become tumor-specific Tregs, whereas CTLA4 blockade alone failed to promote T helper differentiation. Overcoming their paralysis established long-term tumor control, demonstrating a novel immune evasion mechanism that specifically cripples CD4 TTScells to favor tumor progression.
Cytomixis and aberrant phenomena during meiosis in pollen mother cells ofCamellia sinensisvar.sinensiscv ‘Fudingdabai’
Authors: Yu Xuelian , You Xinhan , Zhang Lixia , Li Xingfeng 
Published: April 2023

AbstractTea plant (Camellia sinensis) is an economically essential crop in China, Japan and other countries. The present study reports the meiotic behavior, including microsporogenesis of the ‘Fudingdabai’ cultivar inCamellia sinensisvar.sinensis. Most of the investigated pollen mother cells undergo normal meiosis processes. In contrast, a few of the pollen mother cells showed some abnormal phenomena such as cytomixis, monovalent, laggard chromosomes, unsynchronized division, micronucleus, and so on. Among which, spontaneous cytomixis is the most common phenomenon, which mainly occurred in early prophase I but also in meiosis II. Other abnormal phenomena were less than cytomixis. The results of this study laid a foundation for exploring the meiosis and cytogenetics study of the tea plants.
A workcell 1.0 for programmable and controlled operation of multiple fluidic chips in parallel
Authors: Ning Chuanfang , Bunke Gabriel , Lietar Simon , van den Heuvel Lukas , Shahein Amir 
Published: April 2023

AbstractWe developed a versatile lab-on-chip (LOC) workcell that enables the design and automatic execution of experiments on LOC devices, improving how we establish, optimize, and productionalize LOC processes. Key features include direct docking and cooling of native laboratory tubes, programmable reagent mixing and dilutions, parallel operation of multiple chips, precise flowrate and pressure control, clogging detection and response, programmable microscope control, chip temperature regulation, and scheduled cleaning. All functionality is controlled seamlessly from an easy-to-write protocol file, and based on extensible hardware and software infrastructures to promote community development. To showcase the platform’s use and versatility, we demonstrate a series of 5 different automated experiments at varying levels of complexity, executed across both Quake-valve and droplet microfluidic systems. In particular, the workcell was instructed to map the parameter regime that generates viable droplets, to allow a user to select diameters and production frequencies of interest for single bacterial cell encapsulation. Furthermore, three out of three days in a row, the platform successfully performed a complex 15.5h long experiment, integrating in a single automated protocol the full core workflow required by a typical protein-characterization lab: protein expression, purification, dilution generation, and quantitative binding characterization (generating 55296 images in the process). Experiments conducted through the workcell are easier to set up, offer increased control over experiment conditions and parameters, and can be heavily parallelized.
FAO-supported OxPhos leukemic stem cells are sensitive to cold
Authors: Griessinger Emmanuel , Pereira-Martins Diego , Nebout Marielle , Bosc Claudie , Saland Estelle , Boet Emilie , Sahal Ambrine , Chiche Johanna , Debayle Delphine , Fleuriot Lucille , Pruis Maurien , De Mas Véronique , Vergez François , Récher Christian , Huls Gerwin , Sarry Jean-Emmanuel , Schuringa Jan Jacob , Peyron Jean-François 
Published: April 2023

AbstractTargeting mitochondrial oxidative phosphorylation (OxPhos) metabolism has revealed a potential weakness for leukemic stem cells (LSCs) that can be exploited for therapeutic purposes. Fatty acids oxidation (FAO) is a crucial OxPhos-fueling catabolic pathway for some AML and for chemotherapy-resistant AML cells. Here, we identified cold sensitivity at 4°C (cold killing challenge: CKC4), as a novel vulnerability that selectively kills FAO-supported OxPhos LSCs in Acute Myeloid Leukemia while sparing normal hematopoietic stem cells (HSCs). Cell death of OxPhos leukemic cells was induced by membrane permeabilization at 4°C while by sharp contrast, leukemic cells relying on glycolysis were resistant. Forcing glycolytic cells into OxPhos metabolism sensitized them to CKC4. We show using lipidomic and proteomic analyzes that OxPhos shapes the composition of the plasma membrane and introduce variation of 22 lipid subfamilies between cold-sensitive and cold-resistant cells. Cold sensitivity is a potential OxPhos biomarker.SignificanceThis study reveals that mitochondrial energetics fueled by FAO metabolism introduces membrane fragility upon cold exposure in OxPhos-driven AMLs and in LSCs. This novel physical property of Leukemic cells and LSCs opens new avenues for biomarker and diagnostics as well as for anti-OxPhos drug screening and LSCs targeting.One Sentence SummaryOxPhos leukemic cells die at 4°C
Automatic measurement of cardiothoracic ratio in chest x-ray images with ProGAN-generated dataset
Authors: Kusakunniran Worapan , Saiviroonporn Pairash , Siriapisith Thanongchai , Tongdee Trongtum , Uraiverotchanakorn Amphai , Leesakul Suphawan , Thongnarintr Penpitcha , Kuama Apichaya , Yodprom Pakorn 
Published: April 2023

PurposeThe cardiomegaly can be determined by the cardiothoracic ratio (CTR) which can be measured in a chest x-ray image. It is calculated based on a relationship between a size of heart and a transverse dimension of chest. The cardiomegaly is identified when the ratio is larger than a cut-off threshold. This paper aims to propose a solution to calculate the ratio for classifying the cardiomegaly in chest x-ray images.Design/methodology/approachThe proposed method begins with constructing lung and heart segmentation models based on U-Net architecture using the publicly available datasets with the groundtruth of heart and lung masks. The ratio is then calculated using the sizes of segmented lung and heart areas. In addition, Progressive Growing of GANs (PGAN) is adopted here for constructing the new dataset containing chest x-ray images of three classes including male normal, female normal and cardiomegaly classes. This dataset is then used for evaluating the proposed solution. Also, the proposed solution is used to evaluate the quality of chest x-ray images generated from PGAN.FindingsIn the experiments, the trained models are applied to segment regions of heart and lung in chest x-ray images on the self-collected dataset. The calculated CTR values are compared with the values that are manually measured by human experts. The average error is 3.08%. Then, the models are also applied to segment regions of heart and lung for the CTR calculation, on the dataset computed by PGAN. Then, the cardiomegaly is determined using various attempts of different cut-off threshold values. With the standard cut-off at 0.50, the proposed method achieves 94.61% accuracy, 88.31% sensitivity and 94.20% specificity.Originality/valueThe proposed solution is demonstrated to be robust across unseen datasets for the segmentation, CTR calculation and cardiomegaly classification, including the dataset generated from PGAN. The cut-off value can be adjusted to be lower than 0.50 for increasing the sensitivity. For example, the sensitivity of 97.04% can be achieved at the cut-off of 0.45. However, the specificity is decreased from 94.20% to 79.78%.
Better performance after mergers and acquisitions? The case of US farmer cooperatives
Authors: Grashuis Jasper 
Published: April 2023

PurposeThis study analyzes the long-term effect of merger and acquisition (M&A) activity on the profitability, efficiency and liquidity of the largest 500 farmer cooperatives in the United States.Design/methodology/approachSecondary data from the U.S. Department of Agriculture are complemented with primary data collected from print media publications about M&A activity by US farmer cooperatives. The analysis is based on group comparisons of means and distributions to study the effect of M&A activity on financial performance.FindingsFarmer cooperatives with M&A activity generally have lower profitability, efficiency and liquidity than farmer cooperatives without M&A activity, both at the time of the merger or acquisition as well as afterward. Marketing cooperatives in particular perform worse following M&As. Also, the post-merger performance of farmer cooperatives with M&A activity is not affected by the profitability, efficiency or liquidity of the target.Originality/valueResearch on the post-merger performance of farmer cooperatives is both scarce and dated. This study analyzes the effect of M&A activity for a relatively large sample and a relatively long time period (2005–2020).
Mediating effect of innovation capability between entrepreneurial resources and micro business performance
Authors: Taleb Taleb S.T. , Hashim Norashidah , Zakaria Norria 
Published: April 2023

Purpose
This study aims to examine the effect of entrepreneurial resources on micro businesses and the mediating role of innovation capability in this relationship.

Design/methodology/approach
A structured questionnaire was used to gather data for this quantitative study, which adopted partial least squares structural equation modelling to test the hypotheses on a sample of 455 women entrepreneurs in Malaysia.

Findings
The results reveal that entrepreneurial resources, particularly technical resources, positively and significantly affect innovation capability and enhance business performance. Furthermore, innovation capability mediates the relationship between entrepreneurial resources and microbusiness performance.

Research limitations/implications
This study contributes theoretically by combining six entrepreneurial resources into a single framework in light of the resource-based view and finance-based theory. The results corroborate the effects of entrepreneurial resources on the performance of women’s micro businesses and the mediating role of innovation capability in this relationship. However, the cross-sectional design study limited this study’s ability to engage respondents in a more in-depth analysis of pertinent themes.

Practical implications
This research provides guidance and directions for business managers/owners and decision makers to adopt and improve entrepreneurial resources to achieve superior performance and competitive advantages. It presents evidence of innovation capability’s significant role in converting resources into innovative outcomes and creating value. Additionally, it is useful for policymakers to design development programmes for micro, small and medium enterprises (MSMEs) in emerging markets.

Social implications
This study highlights the value of innovation with a variety of entrepreneurial resources for women business owners that significantly impact Malaysian employment and gross domestic product and may have a positive social impact by enhancing social life in local communities. The nation’s unique context of multiracial and ethnic groups reflects Malaysia’s truly Asian ethnic composition.

Originality/value
This study fills the research gap by offering empirical evidence of the mediating role of innovation capability in the link between entrepreneurial resources and microbusiness performance, thus significantly contributing to emerging markets worldwide, where women-owned micro businesses are increasingly generating value and employment.
Extrapolative time-series modelling of house prices: a case study from Sydney, Australia
Authors: Herath Shanaka , Mangioni Vince , Shi Song , Ge Xin Janet 
Published: April 2023

Purpose
House price fluctuations send vital signals to many parts of the economy, and long-term predictions of house prices are of great interest to governments and property developers. Although predictive models based on economic fundamentals are widely used, the common requirement for such studies is that underlying data are stationary. This paper aims to demonstrate the usefulness of alternative filtering methods for forecasting house prices.

Design/methodology/approach
We specifically focus on exponential smoothing with trend adjustment and multiplicative decomposition using median house prices for Sydney from Q3 1994 to Q1 2017. The model performance is evaluated using out-of-sample forecasting techniques and a robustness check against secondary data sources.

Findings
Multiplicative decomposition outperforms exponential smoothing at forecasting accuracy. The superior decomposition model suggests that seasonal and cyclical components provide important additional information for predicting house prices. The forecasts for 2017–2028 suggest that prices will slowly increase, going past 2016 levels by 2020 in the apartment market and by 2022/2023 in the detached housing market.

Research limitations/implications
We demonstrate that filtering models are simple (univariate models that only require historical house prices), easy to implement (with no condition of stationarity) and widely used in financial trading, sports betting and other fields where producing accurate forecasts is more important than explaining the drivers of change. The paper puts forward a case for the inclusion of filtering models within the forecasting toolkit as a useful reference point for comparing forecasts from alternative models.

Originality/value
To the best of the authors’ knowledge, this paper undertakes the first systematic comparison of two filtering models for the Sydney housing market.
Tribology for sustainable solutions: tribometer wear testings of the human dental care tribosystem tooth–bamboo toothbrush–toothpaste
Authors: Reiser Matthias , Beau Patrick , Patzer Gregor , Niessner Matthias 
Published: April 2023

Purpose
Environmentally friendly products are finding a place in everyday lives more frequently, like bamboo toothbrushes. However, the authors find no statement from consumer protection centers about their impact on the human well-being or dental health in daily use. Therefore, this study aims to investigate the tribological parameters between tooth, toothpaste and toothbrush laboratory tests with a focus on abrasive wear.

Design/methodology/approach
The real-world system was systematically transferred to a laboratory scale, which was implemented to a Schwing-Reib-Verschleiß tribometer tribometer (Optimol Instruments). For an abstraction of the real-world system, as many components of the original tribosystem as possible were retained. In addition, the abstraction was selected so that the method could be transferred to other tribometers. For the evaluation of the test subjects, an optical measurement method was developed to investigate the forms of wear.

Findings
Based on eight test series, it is possible to differentiate between the tribological partners by the wear results. With the help of the measurement method, it will be possible to recommend the use of sustainable oral hygiene products for everyone in everyday life in future. According to the findings, the use of low-cost toothbrushes and highly abrasive toothpaste should be avoided. The effects of an aggressive brushing technique cannot be compensated by gentle toothbrushes and toothpastes.

Originality/value
To the best of the authors’ knowledge, this is the first approach to investigate the wear behavior of tooth–toothpaste–toothbrush while substitute the tooth with dental gypsum. The approach is relevant for developing screening tests with high respect to transferability to the real-world application.

Peer review
The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-11-2022-0339/
How do environmental taxes affect green process innovation? Evidence from the Chinese manufacturing industry
Authors: Wei Lan , Zhang Yanbo , Jia Jinan 
Published: April 2023

PurposeThe absence of government intervention and market supervision cannot effectively promote green process innovation in manufacturing industries. As a new government regulation approach, environmental taxes provide a platform to internalize the externality of environmental pollution. This paper empirically investigates the impact of environmental taxes on green process innovation and the moderating effects of industry pollution heterogeneity and green credit.Design/methodology/approachThis research collects manufacturing industry data ranging from 2008 to 2020, resulting in a total of 351 observations. Time-individual, two-way fixed effect models are constructed to examine the hypotheses.FindingsThe results indicate environmental taxes have an inverted-U effect on green process innovation in manufacturing industries. Implementation intensity of the current environmental taxes on China's manufacturing industries does not reach an inflection point. Further analysis suggests that environmental taxes exert influence on the inverted-U relationship with low-pollution industries displaying a steeper curvilinear pattern than high-pollution industries. Moreover, the analysis shows that green credit plays a moderating role in the inverted-U relationship, as low green credit provides more limited stimulus than high green credit in terms of the effect of environmental taxes on green process innovation.Research limitations/implicationsThis study offers empirical evidence to accommodate negative externalities of corporate production and provides new perspectives in nudging corporate green-process innovation.Originality/valueThis paper verifies the effect of environmental taxes on green process innovation amid industry pollution heterogeneity by introducing an industrial-level analysis unit. This study improves the means by which environmental taxes are measured. Existing literature has narrowly used pollution discharge fees as a proxy for environmental taxes. The authors have summed up the taxes on vehicle and vessels, urban land use, urban maintenance and construction, vehicle purchases, waste gas, wastewater and solid waste to measure the effect of environmental taxes in this study.
Impacts of digital twins on new business creation: insights from manufacturing industry
Authors: Timperi Mira , Kokkonen Kirsi , Hannola Lea , Elfvengren Kalle 
Published: April 2023

Purpose
Digital twins (DTs) and other data-based solutions are gaining an increasing foothold in manufacturing business, whereas a mere physical product is often insufficient to satisfy all customers’ expectations. As a result, companies are seeking novel ways of value creation, and one exciting opportunity is the use of DTs in new business creation, where they can offer diverse possibilities for innovative businesses. This paper aims to examine the impacts and challenges of DTs on new business creation in the manufacturing industry.

Design/methodology/approach
This study used a qualitative research approach, which combined semistructured interviews and an iterative Delphi study as research methods. The participants for the interviews and Delphi study were from different sectors and roles in the manufacturing industry. Altogether, 10 interviewees from eight companies took part in the interviews, and the expert panel of the Delphi method contained 12 professionals.

Findings
The results of the study indicated that DT can significantly impact the business models of manufacturing companies. DT can enhance operations, offer cost savings and business growth and allow stakeholders to focus on core competencies while developing their businesses. Several challenges for leveraging DT were identified, such as data ownership, resource allocation, internal bureaucracy and the difficulty of demonstrating the actual value of data-based services to potential customers.

Originality/value
This paper provides a structured expert-led assessment of the potential impacts of DT utilization in the creation of new business opportunities.