bluuebunny/crossref_metadata_2025_split huggingface dataset:
Master protocols in Low-and-Middle income countries: A review of current use, limitations, and opportunities for precision medicine
Authors: Ouma Luke , Al-Ashmori Sarah , Sarkodie Samuel , Whitehead Lou , Konkoth Ann Breeze , Hiu Shaun , Bigirumurame Theophile , Kareithi Dorcas , Lozano-Kuehne Jingky , Shahmandi Marzieh , Wason James M.S. 
Published: December 2024

AbstractBackgroundMaster protocols - umbrella, basket and platform trials that study multiple therapies, multiple diseases or both, offer many advantages, most profoundly that they answer multiple treatment related questions, that would otherwise take multiple trials. We conducted a review of trial registries to characterise their use in advancing precision medicine in low and middle income countries (LMICs).MethodsWe searched trial records available in 20 trial registries globally, includingClinicalTrials.govand WHO ICTRP, to identify umbrella, basket and platform trials launched until 30 September 2023.ResultsWe identified 102 master protocols - 29 umbrella trials, 31 basket trials, 36 platform trials, as well as 6 other designs that partially aligned with the working definition of master protocols run in 54 different LMICs. Most trials were pharmaceutical industry-sponsored studies (60/102, 58.8%), conducted in oncology settings (56/102, 54.9%), currently ongoing (69/102, 67.6%) in early phase (phase I and II) settings (70/102, 68.6%). There was a greater representation of upper middle-income countries, particularly China that was a site to more than half of all master protocols (53/102, 52%). Other common countries included Brazil, Russia, Turkey and Argentina. Most master protocols (93/102 91.2%) have been planned or launched in the last five years (2019 onwards), mainly with international collaborations in high-income countries. Only a small proportion of trials (5/102, 4.9%) launched exclusively in LMICs excluding china and European LMICs. For most studies, the statistical aspects of trial design and trial documentation (including study protocols and statistical analysis plans) were not publicly accessible.ConclusionUnlike high-income countries, where several hundreds of master protocols are ongoing or completed, there is limited use of master protocols in LMICs, partly owing to low penetration of precision medicine research and limited clinical trial infrastructure in most LMICs. The evidence presented herein create a case for supporting precision medicine initiatives in LMICs (especially Africa), and training and capacity building initiatives focused on innovative clinical trial designs like master protocols, especially in therapeutic areas outside oncology.
Oral supplementation with Nicotinamide Riboside treatment protects RGCs in DBA/2J mouse model
Authors: Zhang Nan , Li Ying , Zhang Xian , Chrenek Micah A. , Wang Jiaxing , Girardot Preston E. , Sellers Jana T. , Brenner Charles , Cui Xiangqin , Geisert Eldon E. , Nickerson John , Boatright Jeffrey H. 
Published: December 2024

AbstractPurposeThe aim of this study was to test whether oral administration of nicotinamide riboside (NR), the nicotinamide adenine dinucleotide (NAD+) precursors, protect retina ganglion cells (RGCs) from neurodegeneration in DBA/2J (D2) mice, which is a widely used mouse model of age-related inherited glaucoma.MethodOral NR or NAM administration (NR low dose: 1150mg/kg; NR high dose: 4200mg/kg; NAM low dose group: 500mg/kg; NAM high dose: 2000mg/kg of body weight per day) essentially started when D2 mice were 4 or 9 months old and continued up to 12 months old. Control cohort identically received food/water without NAM or NR. Intraocular pressure (IOP) was measured every month until experiment completion. Pattern electroretinography (PERG) was recorded. Retinas were harvested for whole mount immunofluorescence staining with RGCs marker Brn3a and imaged by fluorescent confocal microscopy. Optic nerves were harvested for axon staining and quantification. Retinal NAD+ levels were enzymatically assayed.ResultsNR oral supplementary treatment started at 4 months old robustly increased retinal NAD+ levels in D2 mice (NRHighvs. vehicle: 273.7±23.59% vs. 108.70±12.10%,p<0.001). In aged vehicle group (12 months old), there was significantly diminution of the P1 and N2 components of PERG response compare with naïve group (naïve vs. vehicle: P1: 7.82± 0.70uV vs 1.63± 0.17uV,p<0.0001; N2: -13.29± 0.83uV vs. -3.22± 0.27uV,p<0.0001; Kruskal-Wallis test with Dunn‘s multiple comparison test). NR treatment preserved aged D2 visual function when mice were 9 and 12 months old. In addition, long-term NR high dose treatment significantly protected against total RGCs loss and optic nerve atrophy (RGC: NRHighvs. vehicle: 1412±62.00vs 475.2±94.68 cells/field,p<0.00001; axon numbers: NRHighvs. vehicle: 23990±1159 vs 8573±1160, n=41-53,p<0.0001). Furthermore, long-term NR supplementation prevent iris depigmentation and delayed IOP elevation.ConclusionNR oral supplementary treatment significantly preserved RGC and axon numbers, potentially preserves retinal function via elevated retinal NAD+ level in aged D2 mice. Interestingly, NR treatment also prevented iris atrophy, delayed IOP elevation associated with this glaucoma model. NR oral supplementation thus treated several aspects of murine pigment dispersion glaucoma. Given parallels between this model and glaucoma in human, out data indicate that NR is worth exploring as a therapeutic candidate in treatment of glaucoma.
A method for authenticating the fidelity ofCryptococcus neoformansknockout collections
Authors: Jacobs Ella , Dragotakes Quigly , Kulkarni Madhura , Dziedzic Amanda , Jedlicka Anne , Marie Hardwick J. , Casadevall Arturo 
Published: December 2024

AbstractGene knockout strain collections are important tools for discovery in microbiology.Cryptococcus neoformansis the only human pathogenic fungus with an available genome-wide deletion collection, and this resource is widely used by the research community. We uncovered mix-ups in the assembly of the commercially availableC. neoformansdeletion collection of ∼6,000 unique strains acquired by our lab. While pursuing the characterization of a gene-of-interest, the corresponding deletion strain from theC. neoformansKO collection displayed several interesting phenotypes associated with virulence. However, RNAseq analysis identified transcripts for the putative knockout gene, and the absence of transcripts for a different knockout strain found in the same plate position in an earlier partial knockout collection, raising the possibility that plates from one collection were substituted for the other. This was supported by determining the size of the nourseothricin (NAT)-resistance cassette used to generate the two separate knockout libraries and was confirmed by RNAseq and genome sequencing. Here we report that our KN99 collection is comprised of mixed plates from two independent KO libraries and present a simple authentication method that other investigators can use to distinguish the identities of these KO collections.ImportanceGene knockout strain collections are important tools for discovery in microbiology.Cryptococcus neoformansis the only human pathogenic fungus with an available genome-wide deletion collection, and this resource is widely used by the research community. Here we report that our KN99 collection is comprised of mixed plates from two independent KO libraries and present a simple authentication method that other investigators can use to distinguish the identities of these KO collections. Above all, this article serves as a reminder to 2015 library collection strains before undertaking large phenotyping experiments.
Inhibition of RhoA-mediated secretory autophagy in megakaryocytes mitigates myelofibrosis in mice
Authors: Becker Isabelle C. , Barrachina Maria N. , Lykins Joshua , Camacho Virginia , Stone Andrew P. , Chua Bernadette A. , Signer Robert A.J. , Machlus Kellie R. , Whiteheart Sidney W. , Roweth Harvey G. , Italiano Joseph E. 
Published: December 2024

AbstractMegakaryocytes (MKs) are large, polyploid cells that contribute to bone marrow homeostasis through the secretion of cytokines such as transforming growth factor β1 (TGFβ1). During neoplastic transformation, immature MKs accumulate in the bone marrow where they induce fibrotic remodeling ultimately resulting in myelofibrosis. Current treatment strategies aim to prevent MK hyperproliferation, however, little is understood about the potential of targeting dysregulated cytokine secretion from neoplastic MKs as a novel therapeutic avenue. Unconventional secretion of TGFβ1 as well as interleukin 1β (IL1β) via secretory autophagy occurs in cells other than MKs, which prompted us to investigate whether similar mechanisms are utilized by MKs. Here, we identified that TGFβ1 strongly co-localized with the autophagy marker light chain 3B in native MKs. Disrupting secretory autophagy by inhibiting the small GTPase RhoA or its downstream effector Rho kinase (ROCK) markedly reduced TGFβ1 and IL1β secretionin vitro.In vivo, conditional deletion of the essential autophagy geneAtg5from the hematopoietic system limited megakaryocytosis and aberrant cytokine secretion in an MPLW515L-driven transplant model. Similarly, mice with a selective deletion ofRhoafrom the MK and platelet lineage were protected from progressive fibrosis. Finally, disease hallmarks in MPLW515L-transplanted mice were attenuated upon treatment with the autophagy inhibitor hydroxychloroquine or the ROCK inhibitor Y27632, either as monotherapy or in combination with the JAK2 inhibitor ruxolitinib. Overall, our data indicate that aberrant cytokine secretion is dependent on secretory autophagy downstream of RhoA, targeting of which represents a novel therapeutic avenue in the treatment of myelofibrosis.One Sentence SummaryTGFβ1 is released from megakaryocytes via RhoA-mediated secretory autophagy, and targeting this process can alleviate fibrosis progression in a preclinical mouse model of myelofibrosis.
Analyzing Differences in Processing Nouns and Verbs in the Human Brain using Combined EEG and MEG Measurements
Authors: Kölbl Nikola , Müller-Voggel Nadia , Rampp Stefan , Kaltenhäuser Martin , Tzirdis Konstantin , Krauss Patrick , Schilling Achim 
Published: December 2024

AbstractLanguage and consequently the ability to transmit and spread complex information is unique to the human species. The disruptive event of the introduction of large language models has shown that the ability to process language alone leads to incredible abilities and, to some extent, to intelligence. However, how language is processed in the human brain remains elusive. Many insights originate from fMRI studies, as the high spatial resolution of fMRI devices provides valid information about where things happen. Nevertheless, the limited temporal resolution prevents us from gaining a deep understanding on the underlying mechanisms. In this study, we performed combined EEG and MEG measurements in 29 healthy right-handed human subjects during the presentation of continuous speech. We compared the evoked potentials (ERPs and ERFs) for different word types in source space and sensor space across the whole brain. We found characteristic spatio-temporal patterns for different word types (nouns, verbs) especially at latencies of 300ms to 1 s. This is further emphasized by the fact that we observe these effects in two pre-defined sub-samples of the data set (exploration and validation sample). We expect this study to be the starting point for further evaluations of semantic and syntactic processing in the brain.
CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network of Postnatal Atrial Cardiomyocytes
Authors: Sweat Mason E. , Shi Wei , Keating Erin M. , Ponek Anna , Li Jie , Ma Qing , Park Chaehyoung , Trembley Michael A. , Wang Yi , Bezzerides Vassilios J. , Conlon Frank L. , Pu William T. 
Published: December 2024

AbstractAtrial fibrillation (AF) is the most common sustained arrhythmia, affecting 59 million individuals worldwide. Impairment of atrial cardiomyocyte (aCM) gene regulatory mechanisms predisposes to atrial fibrillation. The transcription factor TBX5 is essential for normal atrial rhythm, and its inactivation causes loss of aCM enhancer accessibility, looping, and transcriptional identity. Here we investigated the mechanisms by which TBX5 regulates chromatin organization. We found that TBX5 recruits CHD4, a chromatin remodeling ATPase, to 33,170 genomic regions (TBX5-enhanced CHD4 sites). As a component of the NuRD complex, CHD4 functions to repress gene transcription. However, combined snRNA-seq and snATAC-seq of CHD4 knockout (KO) and control aCMs revealed that CHD4 has both gene activator and repressor functions. Genes repressed by CHD4 in aCMs included sarcomeric proteins from non-CM cell lineages. Genes activated by CHD4 in aCMs were characterized by TBX5-enhanced CHD4 recruitment, which enhanced chromatin accessibility and promoted the expression of aCM identity genes. This mechanism of TBX5 recruitment of CHD4 was critical for sinus rhythm becauseChd4AKOmice had increased vulnerability to AF from electrical pacing and a fraction had spontaneous AF. Our findings reveal that CHD4 is essential for maintaining aCM gene expression, aCM identity, and atrial rhythm homeostasis.
Research on embroidery style migration model based on texture cycle GAN
Authors: Liu Chengxia , Gu Jiawen , Yao Lan , Zhang Ying 
Published: December 2024

PurposeAs an ancient art form, embroidery has strong practicality and artistic value. However, current embroidery style migration models produce images with unclear textures and a lack of stitch detail. So, in this paper, we propose a cyclic consistent embroidery style migration network with texture constraints, which is called Texture Cycle GAN (TCGAN).Design/methodology/approachThe model is based on the existing Cycle GAN network with an additional texture module. This texture module is implemented using a pre-trained Markovian adversarial network to synthesize embroidery texture features. The overall algorithm consists of two generative adversarial networks (for style migration) and the Markovian adversarial network (for texture synthesis).FindingsQualitative and quantitative experiments show that, compared with the existing convolutional neural network style transfer algorithm, the introduction of the texture-constrained embroidery style transfer model TCGAN can effectively learn the characteristics of style images, generate digital embroidery works with clear texture and natural stitches and achieve more realistic embroidery simulation effects.Originality/valueBy improving the algorithm for image style migration and designing a reasonable loss function, the generated embroidery patterns are made more detailed, which shows that the model can improve the realism of embroidery style simulation and help to improve the standard of embroidery craftsmanship, thus promoting the development of the embroidery industry.
A qualitative study of kindergarten teachers’ views on superintendents’ authority and power
Authors: Harduf Noa , Berkovich Izhak 
Published: December 2024

PurposeThe study aimed to explore the authority and power of kindergarten superintendents in public education to elucidate their leadership dynamics.Design/methodology/approachSemi-structured interviews were conducted with 24 Israeli kindergarten teachers about the authority and power of their superintendents. Thematic analysis was used to construct a description of two overarching authority categories: formal and informal.FindingsWithin the realm of formal authority, two prevalent leadership types were discerned: bureaucratic management and management by exception. Each type incorporated distinct official strategies for influencing kindergarten teachers. Three predominant informal leadership types emerged – authoritarian, empowering and pedagogical – reflecting different unofficial approaches to influencing kindergarten teachers. The study elucidates the power base that underpins each leadership type, describing the resources superintendents use for influence and leverage.Originality/valueThe importance of the study lies in providing valuable insights into the authority and power of kindergarten superintendent leadership in a centralized public early childhood system.
Buyer–supplier TMT background misalignment and green innovation performance: the moderating roles of TMT tenure and incentives
Authors: Yang Yang , Jiang Yan , Chen Linyue 
Published: December 2024

PurposeWhile top management teams (TMTs) play an important role in shaping firms’ strategic choices and performance outcomes, studies on green innovation have rarely considered the influence of the TMT demographics of firms and their suppliers. Drawing upon upper echelon theory, this study investigates the impact of buyer–supplier TMT misalignment on green innovation performance, along with potential moderators of this effect.Design/methodology/approachThe empirical setting is Chinese-listed manufacturing firms that are present in both the Chinese Research Data Services Platform (CNRDS) database and the China Stock Market and Accounting Research (CSMAR) database. The study employs panel data regression methods on a dyadic dataset of 530 paired buyer–supplier firm-year observations over the period 2008–2019.FindingsBuyer–supplier TMT misalignment in terms of functional background and educational level is negatively associated with buyer green innovation performance. This negative effect can, however, be mitigated by TMT tenure and long-term incentives in buyer firms.Originality/valueBy introducing the notion of TMT background misalignment to the supply chain, this study advances the understanding of relational TMT demographics in predicting organizational performance and extends upper echelon theory.
Improving production processes with a customer-centric perspective using a novel hybrid approach in the textile sector
Authors: Sikander Sufyan , Naseem Afshan , Shahzad Asjad , Akhtar Muhammad Jawad , Salman Ali 
Published: December 2024

PurposeIn recent years, especially after the COVID-19 pandemic, home textile production orders decreased significantly. This sudden drop in production has increased industry competition, making customer satisfaction more challenging. As a result, it has become imperative for the industry to deftly navigate such ongoing challenges.Design/methodology/approachThis study examines textile production efficiency methodically. Customer requirements like quality, on-time delivery, better working conditions, cost-effectiveness and facility safety audits are understood first. Quality function deployment (QFD) turns client requirements into technical requirements. Prioritise and analyse risks using Monte Carlo simulation and Pareto charts. Consequently, experts and literature propose corrective measures, which are tested in a pilot run to see how they affect production.FindingsQFD, define, measure, analyse, improve and control (DMAIC) and Monte Carlo simulation were used to reduce high-priority risks and meet client requirements in this study. The house of quality helped relate customers’ requirements and technical requirements. Monte Carlo simulation has also improved risk prioritisation by providing a flexible mathematical structure for identifying and managing the most important risks.Originality/valueThis study is novel in the way it applies this integrated approach to the understudied home textile sector. Unlike traditional DMAIC, this study introduces a novel matrix encompassing all defects. This study offers a data-driven approach to improve product quality, meet customer expectations and reduce prioritised risks in home textile manufacturing.
Embedding ESG in finance education: the impact of ESG education within graduate finance programs on ESG-related problems
Authors: Nurillayev Elnur 
Published: December 2024

Purpose
The purpose of the paper is to determine the extent to which ESG education in graduate finance programs at Kazakhstani universities impacts ESG-related issues incorporating emissions, unemployment rates and corruption.

Design/methodology/approach
This research relies on cross-sectional data for 20 regions of Kazakhstan and 66 universities clustered in those regions for the academic year 2022–2023. This study uses a multiple linear regression method to ascertain the relationship between ESG education and ESG problems.

Findings
Findings indicate that environmental education and overall ESG education have a negative impact on the volume of emissions and the youth unemployment rate. The number of universities is positively related to all three dependent variables representing issues on each aspect of ESG.

Research limitations/implications
I might have omitted some important variables that can play a pivotal role in elucidating ESG-related problems, including the mobility of students from one region to another. Furthermore, the paper analyzed only finance programs at a graduate level, without touching undergraduate-level studies and other programs. Finally, the variables and, hence, the regression results are based on the academic year of 2022–2023; it does not account for the change for the past years and does not include time-series analysis.

Originality/value
This paper is original, as it examines whether ESG education helps to curb ESG-related issues at a national level in Kazakhstan, and the studies on sustainability education in Kazakhstan are limited.
The impact of market orientation and brand storytelling on Shark Tank evaluations – a B2B and large language modeling perspective
Authors: Jayashankar Priyanka , Roy Tirtho , Chattopadhyay Souradeep , Arshad Muhammad Arbab , Sarkar Soumik 
Published: December 2024

Purpose
The purpose of the study is to determine how signals of market orientation and brand storytelling affect the evaluation of start-ups by Shark Tank judges.

Design/methodology/approach
The authors analyzed 430 Shark Tank pitches to test their hypotheses. Their expert annotations based on elements of their conceptual model pave the way for them to deploy a large language model that gives us unique psycholinguistic insights into the start-up pitches.

Findings
The authors find that market responsiveness and external disadvantage and passion and determination in brand storytelling have a significant impact on the evaluations of start-ups by investors.

Research limitations/implications
The research is set in an early-stage venture context in the US.

Practical implications
The research findings on business-to-investor interactions can benefit B2B marketers, start-ups and investors.

Originality/value
Their research which draws conceptual inspiration from the resource-based view of the firm and the signaling theory is unique in that the authors use cutting edge large-language model tools to draw psycholinguistic B2B insights from the Shark Tank interactions.