bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammation in Areas of Fibrosis Precedes Loss of Kidney Function in Lupus Nephritis
Authors: Malvica Silvia , Fenaroli Paride , Lee Chen-Yu , Louis Sarah , Celia Alessandra Ida , Bagnasco Serena , Yang Xiaoping , Hodgin Jeffrey B. , Buyon Jill , Magder Laurence , Petri Michelle ,   the Accelerating Medicines Partnership: RA/SLE Network, Rosenberg Avi , Fava Andrea 
Published: November 2024

ABSTRACTBackgroundInterstitial fibrosis in lupus nephritis (LN) is often infiltrated by immune cells but typically regarded as nonspecific “scar reaction.” This study aimed to investigate the relationship between inflammatory fibrosis and kidney disease progression in LN.MethodsInterstitial fibrosis and tubular atrophy (IFTA) were scored in 124 LN kidney biopsies. Inflammation in areas of IFTA (i-IFTA) was graded 0-3 according to the Banff Classification of Allograft Pathology. Significant glomerular filtration rate (GFR) loss was defined as a decline of >15 ml/min at 3 years from biopsy. Immune cell phenotype was defined by serial immunohistochemistry (13-plex).ResultsIFTA was observed in 88/124 (71%) biopsies, and i-IFTA was identified in 76/88 (86%) cases. The distribution of i-IFTA grades was heterogenous across all IFTA grades. In patients with moderate-to-severe IFTA (>25%), the degree of i-IFTA was associated with a higher risk of significant GFR loss: 0/2 (0%), 1/3 (33%), 3/4 (75%), and 7/9 (78%) for i-IFTA grades 0, 1, 2, and 3, respectively (p = 0.028). Multiplexed histology revealed that i-IFTA was mostly composed of CD163+ macrophages and CD4 T cells, followed by CD8 T cells and granulocytes.ConclusionI-IFTA is frequently observed in LN and is dominated by macrophages and T cells. For patients with baseline IFTA >25%, the degree of i-IFTA emerged as a predictor of GFR loss. These data support the routine scoring of i-IFTA in LN due to its prognostic implications and nominate i-IFTA as a potential therapeutic target.LAY SUMMARYScar tissue often contains immune cells, but we still do not fully understand their role. In lupus nephritis (LN), this is typically dismissed as “nonspecific inflammation”. However, our study analyzed kidney biopsies from 124 people with LN and found that inflammation in scarred areas may predict future kidney function loss. Specifically, we identified a type of immune cell, CD163+ macrophages, that may contribute to scarring and kidney damage. Our findings suggest that routinely assessing inflammation in scarred areas could help predict kidney health in LN patients and highlight a possible new target for therapies to prevent kidney damage.
Parp1deletion rescues cerebellar hypotrophy inxrcc1mutant zebrafish
Authors: Semenova Svetlana A. , Nammi Deepthi , Garrett Grace A. , Margolin Gennady , Sinclair Jennifer L. , Maroofian Reza , Caldecott Keith W. , Burgess Harold A. 
Published: November 2024

AbstractDefects in DNA single-strand break repair are associated with neurodevelopmental and neurodegenerative disorders. One such disorder is that resulting from mutations inXRCC1, a scaffold protein that plays a central role in DNA single-strand base repair. XRCC1 is recruited at sites of single-strand breaks by PARP1, a protein that detects and is activated by such breaks and is negatively regulated by XRCC1 to prevent excessive PARP binding and activity. Loss of XRCC1 leads to the toxic accumulation and activity of PARP1 at single-strand breaks leading to base excision repair defects, a mechanism that may underlie pathological changes in patients carrying deleteriousXRCC1mutations. Here, we demonstrate thatxrcc1knockdown impairs development of the cerebellar plate in zebrafish. In contrast,parp1knockdown alone does not significantly affect neural development, and instead rescues the cerebellar defects observed inxrcc1mutant larvae. These findings support the notion that PARP1 inhibition may be a viable therapeutic candidate in neurological disorders.
Unravelling the functional diversity of type III polyketide synthases in fungi
Authors: Sokolova Nika , Denisov Stepan S. , Hackl Thomas , Haslinger Kristina 
Published: November 2024

AbstractType III polyketide synthases (T3PKSs) are enzymes that produce diverse compounds of ecological and clinical importance. While well-studied in plants and bacteria, only a handful of T3PKSs from fungi have been characterised to date. Here, we developed a comprehensive workflow for kingdom-wide characterisation of T3PKSs. Using publicly available genomes, we mined more than 1000 putative enzymes and analysed their active site architecture and genomic neighbourhood. From there, we selected 37 representative PKS candidates for cell-free expression and prototyping with a diverse set of Coenzyme A activated substrates, revealing unique patterns in substrate and cyclisation specificity, as well as the preferred number of malonyl-Coenzyme A extensions. Using the 341 enzyme-substrate pairs generated in this study, we trained a machine learning model to predict T3PKS substrate specificity and experimentally validated it with an extended panel of non-natural substrates. We anticipate that the model will be useful forin silicoscreening of T3PKSs, while the insight into the product scope of these enzymes offers interesting starting points for further exploration.
Intranasal dantrolene nanoparticles inhibit inflammatory pyroptosis in 5XFAD mice brains
Authors: Bhuiyan Piplu , Zhang Wenjia , Chae Rebecca , Kim Kyulee , St. Louis Lauren , Wang Ying , Liang Ge , Wei Huafeng 
Published: November 2024

AbstractBackgroundThis study investigates the effects of intranasal dantrolene nanoparticles on inflammation and programmed cell death by pyroptosis in 5XFAD Alzheimer’s Disease (AD) mice.Methods5XFAD and wild type (WT) B6SJLF1/J mice were treated with intranasal dantrolene nanoparticles (5 mg/kg), daily, Monday to Friday, for 12 weeks continuously, starting at 9 months of age. Blood and brain were harvested at 13 months of age, one month after completion of 12 weeks intranasal dantrolene nanoparticle treatment. Blood biomarkers function of liver (Alanine transaminase, ALT), kidney (Creatinine), and thyroid (TSH: Thyroid-stimulating hormone) were measured using ELISA. The changes of whole brain tissue proteins on Ca2+release channels on membrane of endoplasmic reticulum (type 2 ryanodine and type 1 InsP3 receptors, RyR-2 and InsP3R-1), lipid peroxidation byproduct malondialdehyde (MDA)-modified proteins, 4-HNE, pyroptosis regulatory proteins (NLR family pyrin domain containing 3 (NLRP3), cleaved caspase-1, full length or N-terminal of Gasdermin D (GSDMD), cytotoxic (IL-1, IL-18, IL-6, TNF-a) and cytoprotective (IL-10) cytokines, astrogliosis (GFAP), microgliosis (IBA-1) and synapse proteins (PSD-95, Synapsin-1) were determined using immunoblotting. Body weights were monitored regularly.ResultsIntranasal dantrolene nanoparticles significantly inhibited the increase of RyR-2 and InsP3R-1 proteins, MDA-modified proteins, 4-NHE, pyroptosis regulatory proteins (NLRP3, cleaved caspase-1, N-terminal GSDMD), cytotoxic cytokine (IL-1β, IL-18, IL-6, TNF-α), biomarkers for astrogliosis (GFAP) and microgliosis (IBA-1), and the decrease of cytoprotective cytokine (IL-10) and synaptic proteins (PSD-95, synpasin-1). Intranasal dantrolene nanoparticles for 12 weeks did not affect blood biomarkers for function of liver, kidney, and thyroid, not did it change body weight significantly.ConclusionIntranasal dantrolene nanoparticles significantly inhibit the increase of RyR-2 and InsP3R-1 Ca2+channel receptor proteins, ameliorate activation of the pyroptosis pathway and pathological inflammation, and the associated loss of synapse proteins. Intranasal dantrolene nanoparticles for three months did not affect liver, kidney and thyroid functions or cause other side effects.
Enhanced Notch dependent gliogenesis and delayed physiological maturation underlie neurodevelopmental defects in Lowe syndrome
Authors: Sharma Yojet , Bhatia Priyanka , Rangappa Gagana , Saha Sankhanil , Raghu Padinjat 
Published: November 2024

AbstractThe activity of signaling pathways is required for coordinated cellular and physiological processes leading to normal development of brain structure and function. Mutations inOCRL, a phosphatidylinositol 4,5 bisphosphate [PIP2] 5-phosphatase leads to the neurodevelopmental disorder, Lowe Syndrome (LS). However, the mechanism by which mutations inOCRLleads to the brain phenotypes of LS is not understood. We find that on differentiation of LS patient derived iPSC, developing neural cultures show reduced excitability along with enhanced P levels of Glial Fibrillary Acidic Protein. Multiomic single-nucleus RNA and ATAC seq analysis of neural stem cells generated from LS patient iPSC revealed an enhanced number of cells with a gliogenic cell state. RNA seq analysis also revealed increased levels ofDLK1, a non-canonical Notch ligand in LS patient NSC associated increased levels of cleaved Notch protein and elevation of its transcriptional targetHES5, indicating upregulated Notch signaling. Treatment of iPSC derived brain organoids with an inhibitor of PIP5K, the lipid kinase that synthesizes PIP2, was able to restore neuronal excitability and rescue Notch signaling defects in LS patient derived organoid cultures. Overall, our results demonstrate a role for PIP2dependent regulation of Notch signaling, cell fate specification and development of neuronal excitability regulated by OCRL activity.
Bwa, an ortholog of alkaline ceramidase-ACER2, promotes intestinal stem cell proliferation through pro-inflammatory cytokine signaling inDrosophila melanogaster
Authors: Rahman M. Mahidur , Kraft Chloe , Clark Collin , Nicholson Rebekah J. , Marchetti Marco , Williams Emily , Zhang Chenge , Holland Will L. , Summers Scott A. , Edgar Bruce A. 
Published: November 2024

ABSTRACTSphingolipids, including ceramides, are an important component of high-fat diets. These molecules can regulate fatty acid oxidation and intestinal stem cell proliferation, predisposing the gut to tumorigenesis. However, the molecular mechanisms involved in ceramide metabolism-mediated intestinal stem cell (ISC) proliferation and tumorigenesis are poorly understood. To understand how changes in sphingolipid metabolite flux affect intestinal stem cells, we manipulated the activities of each of the enzymes of the ceramide synthetic pathway using cell type-specific over-expression or depletion of the corresponding mRNAs in each intestinal cell type of theDrosophilamidgut. We documented cell-autonomous and non-cell-autonomous effects, including alterations in cell size, number, differentiation, and proliferation. In our screen, the altered expression of several ceramide metabolism enzymes led to changes in ISC proliferation, cell sizes, and overall cellularity. Among other genes, over-expression of ceramidase homolog,Brain washing (bwa)in gut enteroblasts (EB) increased EB cell size and caused a non-cell-autonomous, 7-8-fold increase in ISC proliferation. Our analysis confirmed previous reports thatbwadoes not have ceramidase activity, and lipidomic studies indicated thatbwaincreases the saturation status of sphingolipids, free fatty acids, and other lipids. The pro-proliferative effects ofbwacould be counter-acted by depleting a serine palmitoyltransferase,Lace, or a sphingosine acyltransferase,Schlank, which are needed for ceramide synthesis, or by co-expressing a ceramide desaturase enzyme,ifc, indicating that increased saturated ceramides were causal for ISC proliferation and the disruption of gut homeostasis. Accumulating saturated sphingolipids and fatty acids induced inflammatory signaling in the gut, and activated ISC proliferation through the pro-inflammatory cytokines, Upd3 and Upd2. We propose that saturated sphingolipids promote ISC proliferation through pro-inflammatory pathways.
Frugal innovation in women-led family businesses in rural communities
Authors: Sánchez-Medina Patricia S. , Ramírez-Altamirano Dailín Alejandra , ´Reyes-Santiago María del Rosario , Melo-Monterrey Manuel de Jesús , Toledo-Morales Arendi 
Published: November 2024

Purpose
The purpose of this paper is to identify a useful taxonomy of frugal innovation (FI) applied to women-led family businesses in rural communities in Oaxaca, Mexico when confronted with disruptive situations such as the recent COVID-19 pandemic, thus achieving a greater understanding of FI in this context to provide these businesses with strategies that allow them to face crises more effectively.

Design/methodology/approach
The study was cross-sectional and quantitative. A scale was developed and applied to 160 family businesses run by women and located in four rural communities in Oaxaca, Mexico. A review of the literature from the period of 2018–2024 made it possible to identify the essential characteristics of FI.

Findings
Through an exploratory factorial analysis, four types of FIs were identified: new production and marketing models, new methods of operation, new financing methods and new organizational methods. Using a discriminant analysis to establish the functionality of the identified FIs, the authors found that shifting to new financing and organizational methods was more important for the survival of family businesses in times of crisis.

Originality/value
This study highlights the forms of FI that develop in small family businesses led by women; this is important for the survival of the family and the business. The research highlights innovation challenges and opportunities for women entrepreneurs in the global south.
Family roots, green shoots: exploring the impact of work–family interpersonal capitalization on employee green behavior
Authors: Wang Xuefei , Liu Yuxin , Chen Yun , Zhang Rongrong 
Published: November 2024

Purpose
This study aims to explore the influence of extra-workplace factors, specifically work−family interpersonal capitalization, on employee green behavior. Based on the conservation of resources theory, the research sought to understand how resources gained from positive family interactions spill over into the workplace, enhancing green behavior. In addition, the study investigated the mediating role of relational energy and the moderating effects of work green climate and environmental self-accountability, providing a nuanced understanding of the mechanisms involved.

Design/methodology/approach
This study used a multiwave field study combined with an experimental study to investigate the impact of work−family interpersonal capitalization on employee green behavior. Data were collected in several phases to capture changes over time and to understand causal relationships. The multiwave design allowed for observing the dynamic interplay between family and work domains, while the experimental component provided controlled conditions to validate the findings. This approach ensured robust and comprehensive analysis, integrating both real-world and experimental data.

Findings
The study revealed that work−family interpersonal capitalization significantly enhances employee green behavior. Relational energy emerged as a crucial mediator in this relationship. Furthermore, the study found that both work green climate and environmental self-accountability positively moderated the relationship between relational energy and green behavior. Notably, the interaction of work green climate and environmental self-accountability further strengthened this relationship, ultimately influencing the indirect effect of relational energy on employee green behavior. These findings highlight the complex interplay between personal and organizational factors in promoting sustainable practices at work.

Originality/value
This study provides valuable insights into the spillover effects from family to work, emphasizing the importance of considering “nongreen” factors in understanding employee green behavior. By identifying relational energy as a key mediator and uncovering the moderating roles of work green climate and environmental self-accountability, the research contributes to the broader literature on environmental sustainability and organizational behavior. The findings suggest practical implications for organizations aiming to foster green behavior, highlighting the potential of enhancing family−work interactions and cultivating a supportive green work environment.
Quantification analysis of high-speed train aerodynamics with geometric uncertainty of streamlined shape
Authors: Liu Hongkang , Yu Qian , Li Yongheng , Zhang Yichao , Peng Kehui , Kong Zhiqiang , Zhao Yatian 
Published: November 2024

Purpose
This study aims to get a better understanding of the impact of streamlined high-speed trains (HSTs) with geometric uncertainty on aerodynamic performance, as well as the identification of the key parameters responsible for this impact. To reveal the critical parameters, this study creates a methodology for evaluating the uncertainty and sensitivity of drag coefficient induced by design parameters of HST streamlined shapes.

Design/methodology/approach
Bézier curves are used to parameterize the streamlined shape of HSTs, and there are eight design parameters required to fit the streamlined shape, followed by a series of steady Reynolds-averaged Navier–Stokes simulations. Combining the preparation work with the nonintrusive polynomial chaos method results in a workflow for uncertainty quantification and global sensitivity analysis. Based on this framework, this study quantifies the uncertainty of drag, pressure, surface friction coefficient and wake flow characteristics within the defined ranges of streamline shape parameters, as well as the contribution of each design parameter.

Findings
The results show that the change in drag reaches a maximum deviation of 15.37% from the baseline, and the impact on the tail car is more significant, with a deviation of up to 23.98%. The streamlined shape of the upper surface and the length of the pilot (The device is mounted on the front of a train’s locomotive and primarily serves to remove obstacles from the tracks, thereby preventing potential derailment.) are responsible for the dominant factors of the uncertainty in the drag for HSTs. Linear regression results show a significant quadratic polynomial relationship between the length of the pilot and the drag coefficient. The drag declines as the length of the pilot enlarges. By analyzing the case with the lowest drag, the positive pressure area in the front of pilot is greatly reduced, while the nose tip pressure of the tail is enhanced by altering the vortices in the wake. The counter-rotating vortex pair is significantly attenuated. Accordingly, exerts the impacts caused by geometric uncertainty can be found on the wake flow region, with pressure differences of up to 900 Pa. The parameters associated with the shape of the upper surface contribute significantly to the uncertainty in the core of the wake separation region.

Originality/value
The findings contribute to a better understanding of the impact of streamlined HSTs with geometric uncertainty on aerodynamic performance, as well as the identification of the key parameters responsible for this impact. Based on this study, future research could delve into the detailed design of critical areas in the streamlined shape of HSTs, as well as the direction of shape optimization to more precisely and efficiently reduce train aerodynamic drag under typical conditions.
Zakat in metaverse? Evidence from cyberspace
Authors: Hudaefi Fahmi Ali 
Published: November 2024

Purpose
This study aims to explore the recent state of zakat metaverse innovation from unstructured data available in cyberspace, i.e. YouTube, Instagram, X (Twitter), Facebook, LinkedIn and Google.

Design/methodology/approach
This study used “zakat metaverse” keywords to harvest unstructured data and analysed using a mixed-method approach. First step of the analysis applied quantitative text analytics via machine learning tool, followed by the final step of qualitative inductive analysis.

Findings
Quantitative text analytics identified keywords related to zakat metaverse innovation, whereas qualitative analysis explored the critical insights behind those keywords, presented in thematic interpretation.

Research limitations/implications
This study only used unstructured internet data, in which other relevant information may not be covered.

Practical implications
Shariah evaluation of zakat obligations from virtual assets requires the relevantisation of fiqh (Islamic jurisprudence) zakat, which opens future debates.

Social implications
Many zakat institutions operate in emerging economies where digital poverty occurs, and such zakat metaverse innovation would potentially contribute to this digital divide. The relevance of such innovation becomes a major question regarding its inclusivity.

Originality/value
This study combines machine learning analytics and qualitative analysis to explore the recent state of metaverse innovation in zakat administration.
Exploring the effect of transformational leadership and knowledge management in enhancing innovative performance: a mediating role of innovation capability
Authors: Harsono Teguh Widhi , Hidayat Kadarisman , Iqbal Mohammad , Abdillah Yusri 
Published: November 2024

PurposeIn the highly competitive sector of state-owned enterprises in Indonesia, particularly within the electricity group, innovation is crucial for sustainability and growth. This study investigates the impact of transformational leadership and knowledge management on innovation performance, emphasizing the mediating role of innovation capability.Design/methodology/approachEmploying a quantitative approach, this research focuses on the upper management of 11 companies, gathering data from 196 out of 280 surveyed individuals through structured questionnaires. Structural equation modeling (SEM) was utilized for analysis.FindingsOur analysis reveals a dual role of transformational leadership; while it significantly enhances innovation capability, it unexpectedly detracts from innovation performance. Conversely, knowledge management boosts both innovation capability and performance. Significantly, innovation capability serves as a crucial mediator, amplifying the effects of both transformational leadership and knowledge management on innovation performance. These results highlight complex interdependencies within organizational leadership and knowledge frameworks.Practical implicationsThese findings can guide organizations in refining leadership and knowledge management strategies to bolster innovation. By enhancing transformational leadership skills, implementing robust knowledge management systems and fostering innovation capabilities, companies can better navigate the complexities of the modern market. The adaptation of these strategies should consider specific organizational cultures and market dynamics to optimize performance.Originality/valueThis research extends the resource-based view (RBV) by detailing the interplay between key organizational variables, offering fresh insights into their collective impact on innovation within the context of state-owned enterprises in Indonesia.
Exploring the strategic nature of the SENCo's role and the management of education and health care plans since the Covid‐19 pandemic
Authors: Kilbride Debbie , Cotier Tanya , Malthouse Richard 
Published: November 2024

AbstractThis research identifies new approaches to education health and care plan (EHCP) provision since the start of the Covid‐19 (C‐19) pandemic (March 2020 to March 2021). This qualitative research was conducted after the C‐19 pandemic and used online questionnaires to identify the perceptions of 64 SENCos recruited from mainstream primary and secondary schools across southeast London and Essex in England. Thirteen of the 64 participants then consented to be interviewed. The findings show that where SENCos had the autonomy to act strategically, they could enact change for pupils with EHCPs as well as SEND. Furthermore, aspects of practice relating to staff SEND knowledge and understanding of SEND provision were enhanced during the pandemic, as was the SENCo's ability to adapt and allocate resources effectively.