bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imaging Drug Resistance in Juvenile Myoclonic Epilepsy with MRI-derived Cortical Markers
Authors: Pimentel Bernardo Crespo , Kuchukhidze Giorgi , Xiao Fenglai , Caciagli Lorenzo , Höfler Julia , Rainer Lucas , Kronbichler Martin , Vollmar Christian , Duncan John S , Trinka Eugen , Koepp Matthias , Wandschneider Britta 
Published: December 2023

AbstractJuvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsy (IGE) syndrome and can present a significant clinical challenge due to lack of seizure control and concomitant neuropsychological impairment. Its underlying mechanisms remain poorly understood. MRI studies have described structural changes in individuals with IGE syndromes but have so far not identified a distinct structural profile associated with drug resistant IGE. In this cross-sectional case-control neuroimaging analysis we included 79 participants with JME recruited at two European epilepsy centres, 43 of whom were drug resistant, as defined by recurrent seizures in the last 12 months despite adequate trials of at least two antiseizure medications (ASM), a drug sensitive group (n=37), and 78 healthy controls. Participants underwent T1-weighted MRI and a comprehensive neuropsychological test battery including measures within two different domains: verbal memory and executive function. We performed vertex-wise measurements of cortical thickness and neurodevelopmental cortical measures, i.e. white matter surface area and local gyrification index (LGI), through a surface-based framework with subsequent correction of scanner-related effects. Group comparisons (family-wise error (FWE) corrected atp<0.05, family-wise error corrected) showed an increase of surface area in prefrontal, cingulate and temporal regions with left-sided predominance accompanied by increased LGI in the left temporal lobe in drug-resistant compared to drug-responsive individuals with JME. Performance on executive function in participants with drug resistant JME was reduced compared to drug sensitive JME (pBonferroni<0.01) and controls (pBonferroni<0.001). Impaired executive function correlated with increased surface area in medial prefrontal and temporal cortical regions (r< -0.75,p<0.01) after adjusting for disease duration and total ASM load. In conclusion, we identified a cognitive-developmental profile in drug resistant JME characterized by left-weighted changes in surface area and cortical folding complexity, the extent of which correlates with the degree of executive dysfunction. Our results shed further light onto the pathophysiological mechanisms of JME and suggest a neurodevelopmental/network basis for both drug refractoriness and cognitive impairment.
The genetic basis of hydrocephalus: genes, pathways, mechanisms, and global impact
Authors: Hale Andrew T. , Boudreau Hunter , Devulapalli Rishi , Duy Phan Q. , Atchley Travis J. , Dewan Michael C. , Goolam Mubeen , Fieggen Graham , Spader Heather L. , Smith Anastasia A. , Blount Jeffrey P. , Johnston James M. , Rocque Brandon G. , Rozzelle Curtis J. , Chong Zechen , Strahle Jennifer M. , Schiff Steven J. , Kahle Kristopher T. 
Published: December 2023

AbstractHydrocephalus (HC) is a heterogenous disease characterized by alterations in cerebrospinal fluid (CSF) dynamics that may cause increased intracranial pressure. HC is a component of a wide array of genetic syndromes as well as a secondary consequence of brain injury (intraventricular hemorrhage (IVH), infection, etc.), highlighting the phenotypic heterogeneity of the disease. Surgical treatments include ventricular shunting and endoscopic third ventriculostomy with or without choroid plexus cauterization, both of which are prone to failure, and no effective pharmacologic treatments for HC have been developed. Thus, there is an urgent need to understand the genetic architecture and molecular pathogenesis of HC. Without this knowledge, the development of preventive, diagnostic, and therapeutic measures is impeded. However, the genetics of HC is extraordinarily complex, based on studies of varying size, scope, and rigor. This review serves to provide a comprehensive overview of genes, pathways, mechanisms, and global impact of genetics contributing to all etiologies of HC in humans.
Expression profile analysis of COVID-19 patients
Authors: Shimansky Valentin S. , Popov Oleg S. , Klochkova Tatiana G. , Apalko Svetlana V. , Sushentseva Natalya N. , Anisenkova Anna Yu. , Mosenko Sergey V. , Shcherbak Sergey G. 
Published: December 2023

ABSTRACTThe course of COVID-19 is determined by various factors. Studies worldwide have shown a correlation between changes in the expression profile and the severity of the disease. Thus, an in-depth study of differentially expressed genes will allow a more detailed investigation of the metabolic changes occurring in the background of coronavirus infection. The technique of RNA sequencing and subsequent bioinformatics analysis is suitable for such research tasks. In our study, we compared groups of samples from patients with mild and severe disease course and identified a number of differentially expressed genes. These genes are involved in metabolic pathways responsible for immune response, signaling, intercellular communication, metabolism of various compounds etc. We then identified master regulators whose function and role in pathways enriched by differentially expressed genes makes them potential targets for biochemical and meta-studies.
Structural basis of anticancer drug recognition and amino acid transport by LAT1
Authors: Lee Yongchan , Jin Chunhuan , Ohgaki Ryuichi , Xu Minhui , Ogasawara Satoshi , Warshamanage Rangana , Yamashita Keitaro , Murshudov Garib , Nureki Osamu , Murata Takeshi , Kanai Yoshikatsu 
Published: December 2023

AbstractLAT1 (SLC7A5) transports large neutral amino acids and their derivatives across the plasma membrane and plays pivotal roles in cancer cell proliferation, immune response and drug delivery across the blood-brain barrier. Despite recent advances in structural understanding of LAT1, how it discriminates substrates and inhibitors including the clinically relevant anticancer drugs remains elusive. Here we report six structures of LAT1, captured in three different conformations and bound with diverse bioactive ligands, elucidating its substrate transport and inhibitory mechanisms. JPH203, also known as nanvuranlat or KYT-0353 and currently in clinical trials as an anticancer drug, binds to the wide-open substrate-binding pocket of LAT1. It adopts a U-shaped conformer, with its amino-phenylbenzoxazol moiety pushing against transmembrane helix 3 (TM3), bending TM10 and arresting the transporter in the outward-facing conformation. In contrast, the physiological substrate L-Phe does not exhibit such inhibitory interactions, whereas melphalan, a slow substrate, poses steric hindrance in the pocket, explaining its inhibitory activity. Unexpectedly, the “classical” system L inhibitor BCH induces an occluded state, a key structural intermediate required for substrate transport.Transstimulation assays show that BCH facilitates transporter turnover and is therefore a transportable substrate. These findings provide a structural framework for the intricate mechanisms of substrate recognition and inhibition of LAT1, paving the way for developing more specific and effective drugs against it.
AP-2α/AP-2β transcription factors are key regulators of epidermal homeostasis
Authors: Zhang Hui , Raymundo Jackelyn , Daly Kathleen E. , Zhu Wenjuan , Senapati Bill , Marneros Alexander G. 
Published: December 2023

ABSTRACTAP-2 transcription factors regulate ectodermal development but their roles for epidermal homeostasis in the adult skin are unknown. We find that AP-2α is the predominant AP-2 family member in adult epidermis, followed by AP-2β. Through inactivation of AP-2α, AP-2β, or both in keratinocytes we assessed the effects of a gradient of epidermal AP-2 activity on skin function. We find that (1) loss of AP-2β in keratinocytes is compensated for by AP-2α, (2) loss of AP-2α impairs terminal keratinocyte differentiation and hair morphogenesis, and (3) the combined loss of AP-2α/AP-2β results in more severe skin and hair abnormalities. Keratinocyte differentiation defects precede a progressive neutrophilic skin inflammation. Inducible inactivation of AP-2α/AP-2β in the adult phenocopies these manifestations. Transcriptomic analyses of epidermis lacking AP-2α or AP-2α/AP-2β in keratinocytes demonstrate a terminal keratinocyte differentiation defect with upregulation of alarmin keratins and of several immune pathway regulators. Moreover, our analyses suggest a key role of loss of AP-2α-dependent gene expression of CXCL14 and KRT15 as an early pathogenic event towards the manifestation of skin inflammation. Thus, AP-2α/AP-2β are critical regulators of epidermal homeostasis in the adult skin.
Calcium influx rapidly establishes distinct spatial recruitments of Annexins to cell wounds
Authors: Nakamura Mitsutoshi , Parkhurst Susan M. 
Published: December 2023

AbstractTo survive daily damage, the formation of actomyosin ring at the wound periphery is required to rapidly close cell wounds. Calcium influx is one of the start signals for these cell wound repair events. Here, we find that rapid recruitment of all threeDrosophilacalcium responding and phospholipid binding Annexin proteins (AnxB9, AnxB10, AnxB11) to distinct regions around the wound are regulated by the quantity of calcium influx rather than their binding to specific phospholipids. The distinct recruitment patterns of these Annexins regulate the subsequent recruitment of RhoGEF2 and RhoGEF3 through actin stabilization to form a robust actomyosin ring. Surprisingly, we find that reduced extracellular calcium and depletion of intracellular calcium affect cell wound repair differently, despite these two conditions exhibiting similar GCaMP signals. Thus, our results suggest that, in addition to initiating repair events, both the quantity and sources of calcium influx are important for precise Annexin spatiotemporal protein recruitment to cell wounds and efficient wound repair.SummaryCells have rapid and robust repair systems to survive daily damage. This study shows that calcium influx regulates the three distinctDrosophilaAnnexin recruitment patterns to the cell wound in order to organize an actomyosin ring for efficient wound closure.
Mechanical Netrin-1-DCC Coupling Mediates Netrin-1–induced Axonal Haptotaxis
Authors: Qiu Zhen , Minegishi Takunori , Aoki Daichi , Abe Kouki , Baba Kentarou , Inagaki Naoyuki 
Published: December 2023

AbstractThe growth cone, a motile structure located at the tip of growing axon, senses extracellular guidance cues and translates them into directional forces that drive axon outgrowth and guidance. Axon guidance directed by chemical cues on the extracellular adhesive substrate is termed haptotaxis. Recent studies reported that netrin-1 on the substrate functions as a haptotactic axon guidance cue. However, the mechanism mediating netrin-1–induced axonal haptotaxis remains unclear. Here, we demonstrate that substrate-bound netrin-1 induces axonal haptotaxis by facilitating physical interactions between the netrin-1 receptor, DCC, and the adhesive substrates. DCC serves as an adhesion receptor for netrin-1. The clutch molecule shootin1a interacted with DCC, linking it to actin filament retrograde flow at the growth cone. Speckle imaging analyses showed that DCC underwent either grip (stop) and retrograde slip on the adhesive substrate. The grip state was more prevalent on netrin-1-coated substrate compared to the control substrate polylysine, thereby transmitting larger traction force on the netrin-1-coated substrate. Furthermore, disruption of the linkage between actin flow and DCC by shootin1 knockout impaired netrin-1-induced axonal haptotaxis. These findings indicate that the directional force for netrin-1–induced haptotaxis is exerted on the substrates through the mechanical coupling between netrin-1 and DCC which occurs asymmetrically under the growth cone.
Extensive remodelling ofXISTregulatory networks during primate evolution
Authors: Cazottes Emmanuel , Alfeghaly Charbel , Rognard Cloé , Loda Agnese , Castel Gaël , Villacorta Laura , Dong Michael , Heard Edith , Aksoy Irène , Savatier Pierre , Morey Céline , Rougeulle Claire 
Published: December 2023

AbstractUnravelling how gene regulatory networks are remodelled during evolution is crucial to understand how species adapt to environmental changes. We addressed this question for X-chromosome inactivation, a process essential to female development that is governed, in eutherians, by theXISTlncRNA and itscis-regulators. To reach high resolution, we studied closely related primate species, spanning 55 million years of evolution. We show that theXISTregulatory circuitry has diversified extensively over such evolutionary timeframe. The insertion of a HERVK transposon has reshuffledXIST3D interaction network in macaque embryonic stem cells (ESC) andXISTexpression is maintained by the additive effects of theJPXlncRNA gene and a macaque specific enhancer. In contrast,JPXis the main contributor toXISTexpression in human ESCs but is not significantly involved inXISTregulation in marmoset ESCs. None of these entities are however under purifying selection, which suggests that neutrally evolving non-coding elements harbour high adaptive potentials.
Organizational environments, work characteristics and employee innovative behavior in the digital age: an fsQCA approach
Authors: Liu Yueyue , Zhang Xu , Xi Meng , Liu Siqi , Meng Xin 
Published: December 2023

Purpose
For start-ups or growing firms, to effectively navigate the unpredictable nature of digital development and achieve superior innovative performance, it is crucial to have a workforce comprised of creative and innovative employees. Drawing upon the principles of social information processing theory, this study aims to investigate whether specific combinations of organizational internal and external environments, as well as work characteristics in the digital age, can foster a high level of employee innovative behavior.

Design/methodology/approach
By collecting a multilevel and multisource data set comprising 693 employees and 88 CEOs from 88 start-ups or growing firms, this study used fuzzy-set qualitative comparative analysis to examine the distinctive configurations associated with achieving a high level of employee innovative behavior.

Findings
The study found that six solutions enabled employees to innovate more effectively, but six solutions led to the absence of employee innovative behavior.

Research limitations/implications
The findings of this study offer important theoretical and practical implications to motivate employee innovative behavior in Chinese enterprises.

Originality/value
First, this study contributes to the literature on employee innovative behavior by addressing the need to explore the impact of the digital context on promoting innovation among employees. Second, this study adds to the existing literature on employee innovation and entrepreneurship by examining multiple organizational contexts and their influence on innovative behavior. Third, this study makes a significant contribution to the field of employee innovative behavior by examining the macroenvironment surrounding digital transformation within enterprises and integrating both internal and external organizational factors.
Limitations of Jiles–Atherton models to study the effect of hysteresis in electrical steels under different excitation regimes
Authors: Atyia Abdelazeem Hassan Shehata , Ghanim Abdelrahman Mohamed 
Published: December 2023

Purpose
The accurate modeling of magnetic hysteresis in electrical steels is important in several electrical and electronic applications. Numerical models have long been known that can correctly reproduce some typical behaviours of these magnetic materials. Among these, the model proposed by Jiles and Atherton must certainly be mentioned. This model is intuitive and fairly easy to implement and identify with relatively few experimental data. Also, for this reason, it has been extensively studied in different formulations. The developments and numerical tests made on this hysteresis model have indicated that it is able to accurately reproduce symmetrical cycles, especially the major loop, but often it fails to reproduce non-symmetrical cycles. This paper aims to show the positive aspects and highlight the defects of the different formulations in predicting the minor loops of electrical steels excited by non-sinusoidal currents.

Design/methodology/approach
The different formulations are applied to different electrical steels, and the data coming from the simulations are compared with those measured experimentally. The direct and inverse Jiles–Atherton models, including the introduction of the dissipative factor approach, are presented, and their limitations are proposed and validated using the measurements of three non-grain-oriented materials. Only the measured major loop is used to identify the parameters of the Jiles–Atherton model. Furthermore, the direct and inverse Jiles–Atherton models were used to simulate the minor loops as well as the hysteresis cycles with direct component (DC) bias excitation. Finally, the simulation results are discussed and compared to measurements for each study case.

Findings
The paper indicates that both the direct and the inverse Jiles–Atherton model formulations provide a good agreement with the experimental data for the major loop representation; nevertheless, both models can not accurately predict the minor loops even when the modification approaches proposed in the literature were implemented.

Originality/value
The Jiles–Atherton model and its modifications are widely discussed in the literature; however, some limitations of the model and its modification in the case of the distorted current waveform are not completely highlighted. Furthermore, this paper contains an original discussion on the accuracy of the prediction of minor loops from distorted current waveforms, including DC bias.
The role of accreditation on financial innovation and business sustainability: a study of AACSB-accredited business schools in the GCC region
Authors: Aldhaen Esra , Braendle Udo 
Published: December 2023

Purpose
Accreditation represents a quality of academic standards and validation, and its impact on business schools is multifaceted. Accredited institutions are widely acknowledged for their higher quality, financial stability, stakeholder acceptance and overall growth compared to non-accredited educational institutions. Given these positive outcomes, this study aims to explore the role of accreditation in fostering financial innovation and business sustainability.

Design/methodology/approach
The study used a qualitative design to understand this relationship, engaging 36 leaders from Advance Collegiate Schools of Business-accredited business schools in the Gulf Cooperation Council region as participants to collect data. Semi-structured interviews were conducted to gain an in-depth understanding of the topic. Data were analysed using the content analysis method.

Findings
That accreditation significantly influences the business sustainability of these schools. In addition, although the direct impact of accreditation on financial innovation may not be immediately apparent, it was observed that financial inflows experienced remarkable growth after obtaining accreditation.

Originality/value
While the effects of accreditation have been thoroughly researched, its influence on financial innovation and business sustainability remains unexplored. This study aims to discern if accredited educational institutions excel in financial innovation and maintaining sustainable business practices. These findings have important implications as they guide university administrators to maximise the benefits of accrediting their business schools.
Cafe Galavis: a brand with the aroma of innovation
Authors: Perez Perez Juan Ernesto 
Published: December 2023

Learning outcomes
Upon completion of the case study, the students will be able to analyze the brand equity construct through the associative neural network model for decision-making; identify prospective scenarios through the Delphi method for the construction of strategic plans in organizations; and propose the innovation of a product by applying creativity techniques to enter international markets.

Case overview/synopsis
Cafe Galavis was one of the leading family businesses in industrial development and had the highest business recognition, with a century of experience in producing and commercializing roasted and ground coffee in Cucuta, Colombia. In 2015, the diplomatic crisis between the governments of Colombia and Venezuela led to the indefinite closure of the Colombian–Venezuelan border, which caused an increase in income from smuggled coffee. In addition, the presence of different competitors and traditional brands negatively impacted the level of sales, which considerably affected financial stability. Likewise, internal difficulties of family nature and administrative management led to the change of senior management. By 2016, Juan Yáñez was appointed chief executive officer (CEO) and was in charge of avoiding the company’s closure. In January 2023, he received feedback from his consulting team, and upon evaluation of the new market challenges with his collaborators, he realized a great challenge that merited the search for a priority alternative solution. How to design a new product considering the loss of brand identity in the face of the generational change of its consumers? These were some of the challenges posed by the CEO that consequently required starting a strategic management process of innovation.

Complexity academic level
The teaching case is aimed at students of postgraduate academic programs in the areas of knowledge of innovation, product design, industrial design, marketing or MBA. In the modules of marketing, strategic management, brand management and strategic foresight, the case allowed for the orientation of the concepts of brand value or branding as well as the analysis of the value chain for the implementation of strategies that promote competitive advantages of companies. Similarly, in the modules of product or service design, creativity and innovation and complex thinking, the case allows one to approach a complex problem and apply creativity techniques for its solution.

Supplementary material
Teaching notes are available for educators only.

Subject code
CSS: 8 Marketing.
Toward the sustainable development of corporate universities: the case of South Korea
Authors: Oh Jeong Rok , Park Cho Hyun , Baek Kyungmin 
Published: December 2023

Purpose
Despite the burgeoning interest in corporate universities (CUs), their pragmatic application and ongoing evolution present challenges. This study aims to analyze the South Korean CU landscape from a balanced perspective to draw implications for the sustainable development of CUs.

Design/methodology/approach
The study uses a case study method to systematically explore CUs in South Korea by reviewing the South Korean government reports on CUs. The cases of CUs are analyzed based on the holistic model of CUs, which functions as an analytical framework.

Findings
By analyzing four groups of CUs, namely, in-house colleges, corporation colleges, technical colleges and in-house college-type lifelong educational establishments, implemented in South Korea, this study draws implications for the sustainable development of CUs, using the holistic CU model.

Originality/value
By analyzing cases of CUs from a new perspective, this study contributes to expand knowledge on CUs and suggests implications for organizations aiming to establish and sustain their own CUs tailored to their specific needs. Furthermore, this paper delves into the support necessary for the successful implementation and sustainable development of CUs, spanning organizational/team, national and individual levels.